Citation

<1>
Accession Number
641689617
PMID
37364164 [https://www.ncbi.nlm.nih.gov/pubmed/?term=37364164]
Title
Non-alcoholic fatty liver disease: pathophysiological concepts and treatment
options.
Source
Cardiovascular research. (no pagination), 2023. Date of Publication: 26 Jun
2023.
Author
Grander C.; Grabherr F.; Tilg H.
Institution
(Grander, Grabherr, Tilg) Department of Internal Medicine I, Gastroenterology,
Hepatology, Endocrinology & Metabolism, Medical University Innsbruck
Publisher
NLM (Medline)
Subject Headings
adult
article
body weight loss
cancer patient
cardiovascular disease
chronic kidney failure
diabetes mellitus
dysbiosis
epidemic
fatty liver
gastrointestinal tract
human
inflammation
insulin resistance
lifestyle modification
lipotoxicity
liver cell carcinoma
liver cirrhosis
liver fibrosis
metabolic disorder
non insulin dependent diabetes mellitus
*nonalcoholic fatty liver
nonalcoholic steatohepatitis
obesity
outcome assessment
prevalence
endogenous compound
farnesoid X receptor
glucagon like peptide 1
glucagon like peptide 1 receptor
peroxisome proliferator activated receptor agonist
sodium glucose cotransporter 2 inhibitor
Drug Index Terms
endogenous compound [m]; farnesoid X receptor [m]; glucagon like peptide 1 [m];
glucagon like peptide 1 receptor [m]; peroxisome proliferator activated receptor
agonist [m]; sodium glucose cotransporter 2 inhibitor [m]
Other Index Terms
adult [m]; article [m]; body weight loss [m]; cancer patient [m]; cardiovascular
disease [m]; chronic kidney failure [m]; diabetes mellitus [m]; dysbiosis [m];
epidemic [m]; fatty liver [m]; gastrointestinal tract [m]; human [m]; inflammation
[m]; insulin resistance [m]; lifestyle modification [m]; lipotoxicity [m]; liver
cell carcinoma [m]; liver cirrhosis [m]; liver fibrosis [m]; metabolic disorder
[m]; non insulin dependent diabetes mellitus [m]; *nonalcoholic fatty liver [m];
nonalcoholic steatohepatitis [m]; obesity [m]; outcome assessment [m]; prevalence
[m]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is continually
increasing due to the global obesity epidemic. NAFLD comprises a systemic metabolic
disease accompanied frequently by insulin resistance and hepatic and systemic
inflammation. Whereas simple hepatic steatosis is the most common disease
manifestation, a more progressive disease course characterized by liver fibrosis
and inflammation (i.e. non-alcoholic steatohepatitis, NASH) is present in 10-20% of
affected individuals. NAFLD furthermore progresses in a substantial number of
patients towards liver cirrhosis and hepatocellular carcinoma. Whereas this disease
now affects almost 25% of the world's population and is mainly observed in obesity
and type 2 diabetes, NAFLD also affects lean individuals. Pathophysiology involves
lipotoxicity, hepatic immune disturbances accompanied by hepatic insulin
resistance, a gut dysbiosis and commonly hepatic and systemic insulin resistance
defining this disorder a prototypic systemic metabolic disorder. Not surprisingly
many affected patients have other disease manifestations and indeed cardiovascular
disorders (CVD), chronic kidney disease and extrahepatic malignancies are all
contributing substantially to patient outcome. Weight loss and lifestyle change
reflect the cornerstone of treatment and several medical treatment options are
currently under investigation. The most promising treatment strategies include
glucagon-like peptide 1 (GLP-1) receptor antagonists, sodium glucose linked
transporter 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists and
peroxisome-proliferator-activated receptor (PPAR) agonists. Here we review
epidemiology, pathophysiology and therapeutic options for NAFLD.Copyright © The
Author(s) 2023. Published by Oxford University Press on behalf of the European
Society of Cardiology.
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3245&isbn=&volume=&issue=&spage=&pages=&date=2023&title=Cardiovascular+research&ati
tle=Non-alcoholic+fatty+liver+disease
%3A+pathophysiological+concepts+and+treatment+options&aulast=Grander&pid=%3Cauthor
%3EGrander+C.%3BGrabherr+F.%3BTilg+H.%3C%2Fauthor%3E%3CAN%3E641689617%3C%2FAN%3E
%3CDT%3EArticle%3C%2FDT%3E
<2>
Accession Number
641527093
Title
Neck circumference as a simple marker of NAFLD progression in patients with
Metabolic Syndrome.
Source
Obesity Facts. Conference: 30th European Congress on Obesity, ECO 2023. Dublin
Ireland. 16(Supplement 1) (pp 296), 2023. Date of Publication: May 2023.
Author
Palumbo M.; Salvati A.; Brunetto M.; Camastra S.
Institution
(Palumbo, Camastra) Department of Clinical and Experimental Medicine, University
of Pisa, Italy
(Salvati, Brunetto) Hepatology Unit, Santa Chiara Hospital of Pisa, Italy
Publisher
S. Karger AG
Subject Headings
adult
aged
analysis of variance
blood pressure
body mass
body weight
conference abstract
controlled study
elasticity
fat mass
fatty liver index
female
fibrosis
human
human tissue
insulin sensitivity
liver cirrhosis
liver injury
liver stiffness
major clinical study
male
*metabolic syndrome X
multiple regression
*neck circumference
obesity
oral glucose tolerance test
prevalence
regression model
ultrasound
vitamin blood level
waist circumference
young adult
endogenous compound
glucose
high density lipoprotein
insulin
triacylglycerol
uric acid
vitamin D
Drug Index Terms
endogenous compound; glucose; high density lipoprotein; insulin; triacylglycerol;
uric acid; vitamin D
Other Index Terms
adult; aged; analysis of variance; blood pressure; body mass; body weight;
conference abstract; controlled study; elasticity; fat mass; fatty liver index;
female; fibrosis; human; human tissue; insulin sensitivity; liver cirrhosis; liver
injury; liver stiffness; major clinical study; male; *metabolic syndrome X;
multiple regression; *neck circumference; *nonalcoholic fatty liver; obesity; oral
glucose tolerance test; prevalence; regression model; ultrasound; vitamin blood
level; waist circumference; young adult
Abstract
Introduction: Obesity is characterized by a high prevalence of NAFLD, that may
progress to cirrhosis and hepatocellular carcinoma, so identification of advanced
hepatic fibrosis is important. Non-invasive method such as liver stiffness
measurement (LSM) by transient elastography (TE, FibroScan) have been recommended
for exclusion of significant fibrosis. However, TE may not be freely available in
resource-limited settings. The goal of this study was to identify the key
determinants and simple markers of NAFLD progression to fibrosis in patients with
Metabolic Syndrome, a condition shown to have a high prevalence of NAFLD.
Method(s): We examined data from 101 patients among those attending the metabolic
unit, 48 males, 53 females aged 21-78 years. Based on BMI, 4 pts were with normal
weight, 9 with overweight, 58 with obesity. We measured waist circumference (WC),
body weight (BW), BMI, neck circumference (NC), hormonal and metabolic markers.
OGIS index from OGTT was calculated as index of Insulin Sensitivity (IS). Fatty
Liver Index (as an indicator of liver fat) and FIB4 score (as an indicator of
fibrosis) were calculated. In a subgroup of 72 pts the result of liver ultrasound
combined with TE was available for the measurement of LSM indicative of progression
to fibrosis. Based on LSM we divided the population into 3 groups Low Fibrosis
(LSM<=6.6 kPa ndegree 30 pts), Medium Fibrosis (6.6 < LSM <= 12; n 26 pts), High
Fibrosis (LSM >12 kPa; ndegree 16 pts), patients with cirrhosis were excluded. The
groups were compared by ANOVA. Simple and multiple regression analysis were
performed. Result(s): 80% of patients have FLI>60. FLI was directly related to BW,
Fat Mass% (p<0.0001 R 0.69), NC (p<0.0001 R 0.52), Glucose (p 0.08 R 0.27), Insulin
(p= 0.03 R 0.28), Uric Acid (p=0.0003 R 0.39), and inversely correlated to Col HDL
(p= 0.002 R -0.33), OGIS Index (p= 0.001 R -0.41), serum vitamin 25-OH D (p 0.002 r
-0.37). The association with Vitamin D remained after adjusting for the other
factors that characterized MS (Blood Pressure and IS). LSM was directly correlated
to FIB4 (p=0.005), WC, BW, gGT, Glucose, Uric acid, FLI, Triglycerides (for all
p<0.03). In the group of 52 patients for whom NC measurement was available, it was
directly correlated with LSM (p= 0.0002; r=0.56); NC was significantly different in
the 3 groups in relation to the degree of fibrosis (LF 42+/-1cm; MF 44+/-1cm; HF
48+/-2cm; p<0.004). In the same subgroup of patients, in a multiple regression
model NC, BMI, WC and FIB4 Score explained 44% of the variability in liver
elasticity (p= 0.0006; r2=0.44). Adjusting for these variables, NC remains
significantly associated with LSM (p= 0.01), in Stepwise regression model it was
the main determinant of LSM (F = 16.6; p= 0.002). Conclusion(s): In patients with
MS: (a) FLI is elevated in 80% of the population considered and associated with the
main characteristic of MS and Low vitamin D levels. (b) Liver stiffness
measurement, index of liver damage progression, correlates with some metabolic and
anthropometric variables, among them, neck circumference may be an important
predictor of fibrosis in patients with NAFLD when liver cirrhosis has not yet
developed.
T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emexc&AN=641527093
sid=OVID:embase&id=pmid:&id=doi:10.1159%2F000530456&issn=1662-
4033&isbn=&volume=16&issue=Supplement+1&spage=296&pages=296&date=2023&title=Obesity
+Facts&atitle=Neck+circumference+as+a+simple+marker+of+NAFLD+progression+in+patient
s+with+Metabolic+Syndrome&aulast=Palumbo&pid=%3Cauthor%3EPalumbo+M.%3BSalvati+A.
%3BBrunetto+M.%3BCamastra+S.%3C%2Fauthor%3E%3CAN%3E641527093%3C%2FAN%3E%3CDT
%3EConference+Abstract%3C%2FDT%3E
<3>
Accession Number
2023633103
Title
The bidirectional impacts of alcohol consumption and MAFLD for progressive fatty
liver disease.
Source
Therapeutic Advances in Endocrinology and Metabolism. 14 (no pagination), 2023.
Date of Publication: January-December 2023.
Author
Kulkarni A.V.; Sarin S.K.
Author NameID
Sarin, Shiv Kumar; ORCID: https://orcid.org/0000-0002-0544-5610
Institution
(Kulkarni) Department of Hepatology, AIG Hospitals, Hyderabad, India
(Sarin) Department of Hepatology, Institute of Liver and Biliary Sciences, D-1,
Vasant Kunj Rd, New Delhi 110070, India
Publisher
SAGE Publications Ltd
Subject Headings
alcohol abuse
*alcohol consumption
clinical outcome
*fatty liver
human
insulin resistance
*metabolic fatty liver/di [Diagnosis]
nomenclature
obesity
review
Other Index Terms
alcohol abuse; *alcohol consumption; clinical outcome; *fatty liver; human;
insulin resistance; *metabolic fatty liver / *diagnosis; nomenclature; obesity;
Review
Abstract
Nonalcoholic fatty liver disease (NAFLD), once considered a benign condition, has
been associated with several cardiometabolic complications over the past two
decades. The worldwide prevalence of NAFLD is as high as 30%. NAFLD requires the
absence of a "significant alcohol intake." Conflicting reports have suggested that
moderate alcohol consumption may be protective; therefore, the diagnosis of NAFLD
previously relied on negative criteria. However, there has been a significant
increase in alcohol consumption globally. Apart from the rise in alcohol-related
liver disease (ARLD), alcohol, a major toxin, is associated with an increased risk
of several cancers, including hepatocellular carcinoma. Alcohol misuse is a
significant contributor to disability-adjusted life years. Recently, the term
metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed instead
of NAFLD to include the metabolic dysfunction responsible for the major adverse
outcomes in patients with fatty liver disease. MAFLD, dependent on the "positive
diagnostic criteria" rather than previous exclusion criteria, may identify
individuals with poor metabolic health and aid in managing patients at increased
risk of all-cause and cardiovascular mortality. Although MAFLD is less stigmatizing
than NAFLD, excluding alcohol intake may increase the risk of already existing
underreported alcohol consumption in this subgroup of patients. Therefore, alcohol
consumption may increase the prevalence of fatty liver disease and its associated
complications in patients with MAFLD. This review discusses the effects of alcohol
intake and MAFLD on fatty liver disease.Copyright © The Author(s), 2023.
0188&isbn=&volume=14&issue=&spage=&pages=&date=2023&title=Therapeutic+Advances+in+E
ndocrinology+and+Metabolism&atitle=The+bidirectional+impacts+of+alcohol+consumption
+and+MAFLD+for+progressive+fatty+liver+disease&aulast=Kulkarni&pid=%3Cauthor
%3EKulkarni+A.V.%3BSarin+S.K.%3C%2Fauthor%3E%3CAN%3E2023633103%3C%2FAN%3E%3CDT
%3EReview%3C%2FDT%3E
<4>
Accession Number
2023412176
PMID
Title
Citrin Deficiency: Clinical and Nutritional Features.
Source
Nutrients. 15(10) (no pagination), 2023. Article Number: 2284. Date of
Publication: May 2023.
Author
Komatsu M.; Tanaka N.; Kimura T.; Yazaki M.
Author NameID
Tanaka, Naoki; ORCID: https://orcid.org/0000-0002-3212-3836
Yazaki, Masahide; ORCID: https://orcid.org/0000-0001-5520-6530
Institution
(Komatsu) Department of Gastroenterology, Suwa Red Cross Hospital, Nagano, Suwa
392-8510, Japan
(Tanaka) Department of Global Medical Research Promotion, Shinshu University
Graduate School of Medicine, Nagano, Matsumoto 390-8621, Japan
(Tanaka) International Relations Office, Shinshu University School of Medicine,
Nagano, Matsumoto 390-8621, Japan
(Tanaka) Research Center for Social Systems, Shinshu University, Nagano,
Matsumoto 390-8621, Japan
(Kimura) Department of Gastroenterology, Shinshu University School of Medicine,
Nagano, Matsumoto 390-8621, Japan
(Yazaki) Department of Neuro-Health Innovation, Institute for Biomedical
Sciences, Shinshu University, Nagano, Matsumoto 390-8621, Japan
Publisher
MDPI
Subject Headings
clinical feature
clinician
dietitian
fatty liver
human
liver transplantation
nonhuman
*nutritional assessment
*nutritional deficiency/dt [Drug Therapy]
*nutritional deficiency/su [Surgery]
review
steatohepatitis
pyruvate sodium/dt [Drug Therapy]
ursodeoxycholic acid/dt [Drug Therapy]
*citrin deficiency/dt [Drug Therapy]
*citrin deficiency/su [Surgery]
Candidate Terms
*citrin deficiency / *drug therapy / *surgery [other term]
Drug Index Terms
pyruvate sodium / drug therapy; ursodeoxycholic acid / drug therapy
Other Index Terms
clinical feature; clinician; dietitian; fatty liver; human; liver
transplantation; nonhuman; *nutritional assessment; *nutritional deficiency / *drug
therapy / *surgery; Review; steatohepatitis
Abstract
SLC25A13 gene mutations are responsible for diseases related to citrin deficiency
(CD), such as neonatal intrahepatic cholestasis caused by citrin deficiency and
adult-onset type II citrullinemia (CTLN2). From childhood to adulthood, CD patients
are apparently healthy due to metabolic compensation with peculiar dietary habits-
disliking high-carbohydrate foods and liking fat and protein-rich foods.
Carbohydrate overload and alcohol consumption may trigger the sudden onset of
CTLN2, inducing hyperammonemia and consciousness disturbance. Well-compensated
asymptomatic CD patients are sometimes diagnosed as having non-obese (lean) non-
alcoholic fatty liver disease and steatohepatitis, which have the risk of
developing into liver cirrhosis and hepatocellular carcinoma. CD-induced fatty
liver demonstrates significant suppression of peroxisome proliferator-activated
receptor alpha and its downstream enzymes/proteins involved in fatty acid transport
and oxidation and triglyceride secretion as a very low-density lipoprotein.
Nutritional therapy is an essential and important treatment of CD, and medium-chain
triglycerides oil and sodium pyruvate are useful for preventing hyperammonemia. We
need to avoid the use of glycerol for treating brain edema by hyperammonemia. This
review summarizes the clinical and nutritional features of CD-associated fatty
liver disease and promising nutritional interventions.Copyright © 2023 by the
authors.
sid=OVID:embase&id=pmid:37242166&id=doi:10.3390%2Fnu15102284&issn=2072-
6643&isbn=&volume=15&issue=10&spage=2284&pages=&date=2023&title=Nutrients&atitle=Ci
trin+Deficiency%3A+Clinical+and+Nutritional+Features&aulast=Komatsu&pid=%3Cauthor
%3EKomatsu+M.%3BTanaka+N.%3BKimura+T.%3BYazaki+M.%3C%2Fauthor%3E%3CAN
%3E2023412176%3C%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<5>
Accession Number
641424429
PMID
Title
Clinical features of non-alcoholic fatty liver disease in the non-lean
population.
Source
Obesity facts. (no pagination), 2023. Date of Publication: 22 May 2023.
Author
Li M.-R.; Li J.-Z.; Li J.-Y.; Wang C.-C.; Yuan R.-K.; Ye L.-H.; Liu Y.-Y.; Liang
X.-J.; Zhang H.-C.; Liu Z.-Q.; Zeng D.-Y.; Zhang X.-D.; Wang D.-H.; Li J.-Q.; Li
T.-Y.; Yang L.; Cao Y.; Pan Y.; Lin X.-G.; Pan C.Q.; Dai E.-H.; Dong Z.-Y.
Publisher
NLM (Medline)
Subject Headings
adult
*alanine aminotransferase blood level
article
aspartate aminotransferase to platelet ratio index
body mass
*clinical feature
combination index
controlled study
female
fibrosis
gene expression
*histology
histopathology
human
human cell
human tissue
inflammation
liver biopsy
male
obesity
protein expression
prothrombin time
risk factor
alanine aminotransferase
aspartate aminotransferase
cholesterol
endogenous compound
gamma glutamyltransferase
glucose
Drug Index Terms
alanine aminotransferase [m]; aspartate aminotransferase [m]; cholesterol [m];
endogenous compound [m]; gamma glutamyltransferase [m]; glucose [m]
Other Index Terms
adult [m]; *alanine aminotransferase blood level [m]; article [m]; aspartate
aminotransferase to platelet ratio index [m]; body mass [m]; *clinical feature [m];
combination index [m]; controlled study [m]; female [m]; fibrosis [m]; gene
expression [m]; *histology [m]; histopathology [m]; human [m]; human cell [m];
human tissue [m]; inflammation [m]; liver biopsy [m]; major clinical study [m];
male [m]; *nonalcoholic fatty liver [m]; obesity [m]; protein expression [m];
prothrombin time [m]; risk factor [m]
Abstract
INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) in non-
lean patients is significantly increased, and obesity significantly increases the
risk of cirrhosis and HCC in NAFLD patients. However, whether there is a difference
in clinical manifestations of NAFLD between overweight and obesity remains unclear.
The objective of this study was to assess the clinical and histological features of
NAFLD amongst a non-lean population. METHOD(S): Current study enrolled consecutive
non-lean (body mass index (BMI)>23 kg/m2) patients with NAFLD and available liver
biopsy results. Patients were stratified by BMI into two groups for the comparison
of their clinical and histological variables, which included the overweight (BMI
23~<28 kg/m2) and the obese (BMI>=28 kg/m2). Risk factors for moderate to severe
fibrosis (stage>1) were also analysed through the logistic regression model.
RESULT(S): Among 184 non-lean patients with MALFD enrolled,65 and 119 were
overweight and obese, respectively. Patients in the obesity group had a
significantly lower level of gamma-glutamyl transpeptidase (GGT), higher levels of
platelet (PLT), glucose (Glu), prothrombin time (PT), and more common of moderate
to severe inflammatory activity when compared to those in the overweight group.
However, a significant low frequency of moderate to severe fibrosis was found in
the obesity group vs the overweight group (19.33% vs 40.00%, P=0.002). Binary
logistics regression analysis of fibrosis found that aspartate transaminase (AST),
BMI, alanine transaminase (ALT) and cholesterol (CHOL) were independent predictors
for moderate to severe fibrosis in non-lean patients with NAFLD. Compared with the
traditional FIB-4 (AUC=0.77) and APRI (AUC=0.79) indexes, the combined index based
on AST, BMI, ALT and CHOL was more accurate in predicting moderate to severe
fibrosis in non-lean patients with NAFLD (AUC= 0.87). CONCLUSION(S): Clinical and
histological features differed between obesity and overweight patients with NAFLD.
When compared to the traditional serum markers, the combination index including
AST, BMI, ALT and CHOL provided a better model to predict moderate to severe
fibrosis in non-lean patients with NAFLD.Copyright The Author(s). Published by S.
Karger AG, Basel.
sid=OVID:embase&id=pmid:37231905&id=doi:10.1159%2F000530845&issn=1662-
4033&isbn=&volume=&issue=&spage=&pages=&date=2023&title=Obesity+facts&atitle=Clinic
al+features+of+non-alcoholic+fatty+liver+disease+in+the+non-
lean+population&aulast=Li&pid=%3Cauthor%3ELi+M.-R.%3BLi+J.-Z.%3BLi+J.-Y.%3BWang+C.-
C.%3BYuan+R.-K.%3BYe+L.-H.%3BLiu+Y.-Y.%3BLiang+X.-J.%3BZhang+H.-C.%3BLiu+Z.-Q.
%3BZeng+D.-Y.%3BZhang+X.-D.%3BWang+D.-H.%3BLi+J.-Q.%3BLi+T.-Y.%3BYang+L.%3BCao+Y.
%3BPan+Y.%3BLin+X.-G.%3BPan+C.Q.%3BDai+E.-H.%3BDong+Z.-Y.%3C%2Fauthor%3E%3CAN
%3E641424429%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<6>
Accession Number
2024346567
PMID
Title
Mechanisms of non-Alcoholic fatty liver disease development in normal-weight
individuals.
Source
European Journal of Gastroenterology and Hepatology. 35(5) (pp 521-529), 2023.
Date of Publication: 01 May 2023.
Author
Muriel P.; Cardoso-Lezama I.; Vargas-Pozada E.E.; Ramos-Tovar E.
Institution
(Muriel, Cardoso-Lezama, Vargas-Pozada) Laboratory of Experimental Hepatology,
Department of Pharmacology, Cinvestav-IPN, Mexico City, Mexico
(Ramos-Tovar) Seccion de Estudios de Posgrado e Investigacion, Escuela Superior
de Medicina, Instituto Politecnico Nacional, Casco de Santo Tomas, Ciudad de
Mexico, Mexico
Publisher
Lippincott Williams and Wilkins
Subject Headings
adipose tissue
body mass
*body weight
clinical feature
disease classification
disease exacerbation
dysbiosis
gastrointestinal tract
human
insulin resistance
intestine flora
intra-abdominal fat
lipid storage
liver cirrhosis
liver injury
*nonalcoholic fatty liver/ep [Epidemiology]
*nonalcoholic steatohepatitis/ep [Epidemiology]
obesity
prevalence
protein blood level
review
risk factor
serum
skeletal muscle
triacylglycerol blood level
biological marker/ec [Endogenous Compound]
C reactive protein/ec [Endogenous Compound]
insulin/ec [Endogenous Compound]
triacylglycerol/ec [Endogenous Compound]
Drug Index Terms
biological marker / endogenous compound; C reactive protein / endogenous
compound; insulin / endogenous compound; triacylglycerol / endogenous compound
Other Index Terms
adipose tissue; body mass; *body weight; clinical feature; disease
classification; disease exacerbation; dysbiosis; gastrointestinal tract; human;
insulin resistance; intestine flora; intra-abdominal fat; lipid storage; liver
cirrhosis; liver injury; non insulin dependent diabetes mellitus; *nonalcoholic
fatty liver / *epidemiology; *nonalcoholic steatohepatitis / *epidemiology;
obesity; prevalence; protein blood level; Review; risk factor; serum; skeletal
muscle; triacylglycerol blood level
Abstract
While non-Alcoholic fatty liver disease (NAFLD) without inflammation or fibrosis
is considered a relatively 'benign' disease, non-Alcoholic steatohepatitis (NASH),
by contrast, is characterized by marked inflammation in addition to lipid
accumulation, and may include fibrosis, progression to cirrhosis and hepatocellular
carcinoma. Obesity and type II diabetes are frequently associated with NAFLD/NASH;
however, a significant number of lean individuals may develop these diseases.
Little attention has been paid to the causes and mechanisms contributing to NAFLD
development in normal-weight individuals. One of the main causes of NAFLD in
normal-weight individuals is the accumulation of visceral and muscular fat and its
interaction with the liver. Myosteatosis (triglyceride accumulation in the muscle)
induces a loss of muscle by reducing blood flow and insulin diffusion, contributing
to NAFLD. Normal-weight patients with NAFLD exhibit higher serum markers of liver
damage and C-reactive protein levels, as well as more pronounced insulin
resistance, compared to healthy controls. Notably, increased levels of C-reactive
protein and insulin resistance are strongly correlated with the risk of developing
NAFLD/NASH. Gut dysbiosis has also been associated with NAFLD/NASH progression in
normal-weight individuals. More investigation is required to elucidate the
mechanisms leading to NAFLD in normal-weight individuals.Copyright © 2023
Lippincott Williams and Wilkins. All rights reserved.
sid=OVID:embase&id=pmid:36966767&id=doi:10.1097%2FMEG.0000000000002530&issn=0954-
691X&isbn=&volume=35&issue=5&spage=521&pages=521-
529&date=2023&title=European+Journal+of+Gastroenterology+and+Hepatology&atitle=Mech
anisms+of+non-Alcoholic+fatty+liver+disease+development+in+normal-
weight+individuals&aulast=Muriel&pid=%3Cauthor%3EMuriel+P.%3BCardoso-Lezama+I.
%3BVargas-Pozada+E.E.%3BRamos-Tovar+E.%3C%2Fauthor%3E%3CAN%3E2024346567%3C%2FAN%3E
%3CDT%3EReview%3C%2FDT%3E
<7>
Accession Number
641283584
Title
Patient management: risk stratification.
Source
Hepatology International. Conference: 32nd Annual Conference of Asian Pacific
Association for the Study of the Liver. Taipei Taiwan (Republic of China).
17(Supplement 1) (pp S15-S16), 2023. Date of Publication: April 2023.
Author
Huang J.-F.
Institution
(Huang) Hepatobiliary Division, Department of Internal Medicine, Kaohsiung
Medical University Hospital, Kaohsiung, Taiwan (Republic of China)
(Huang) Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung,
Taiwan (Republic of China)
Publisher
Springer
Subject Headings
adult
Asia
Asian
body mass
cancer patient
conference abstract
controlled study
diabetes mellitus
human
insulin resistance
metabolic fatty liver
metabolic syndrome X
nonalcoholic fatty liver
obesity
*patient care
phenotype
prevalence
race
*risk assessment
Taiwan
Other Index Terms
adult; Asia; Asian; body mass; cancer patient; conference abstract; controlled
study; diabetes mellitus; human; insulin resistance; liver cell carcinoma;
metabolic fatty liver; metabolic syndrome X; non insulin dependent diabetes
mellitus; nonalcoholic fatty liver; obesity; *patient care; phenotype; prevalence;
race; *risk assessment; Taiwan
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new definition
of non-alcoholic fatty liver disease (NAFLD) proposed in 2020 by an expert meeting
for the approach of steatosis-centered metabolic fatty liver disorder. The
elucidation of disease progression in terms of disease course, phenotypes and
outcomes is mandatory for clinical management in the aspect of new definition.
Further characterize and stratify MAFLD phenotypes and its drivers will be
mandatory for clinical trials and patient management. Robust evidence demonstrated
that insulin resistance (IR) is the main driver of NAFLD/MAFLD, irrespective of
body mass index (BMI). Previous studies also have indicated that there is a close
relationship between IR and NAFLD, with a five-fold higher prevalence of NAFLD in
patients with type 2 diabetes mellitus (T2DM) compared to patients without T2DM.
Robust evidence showed that T2DM was associated with a twofold increase in risk of
hepatocellular carcinoma (HCC). Recent community-based study from Taiwan
demonstrated that high IR was the predictive factor significantly associated with
NAFLD in both obese and lean subjects. The disease susceptibility and progression
may largely be affected by the ethnic factor, which contribute to the difference of
phenotypic characteristics between different regions. The relative lower BMI in
Asians is not protective from metabolic insults. Moreover, Asian people are more
prone to metabolic syndrome (MetS), T2DM and MAFLD than other races. Therefore,
risk stratification is an essential for patient management in MAFLD. Th measurement
is particularly of importance in Asia- Pacific in parallel to the rapid
Westernization in the region.
T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emexb&AN=641283584
sid=OVID:embase&id=pmid:&id=doi:10.1007%2Fs12072-023-10501-4&issn=1936-
0541&isbn=&volume=17&issue=Supplement+1&spage=S15&pages=S15-
S16&date=2023&title=Hepatology+International&atitle=Patient+management
%3A+risk+stratification&aulast=Huang&pid=%3Cauthor%3EHuang+J.-F.%3C%2Fauthor%3E
%3CAN%3E641283584%3C%2FAN%3E%3CDT%3EConference+Abstract%3C%2FDT%3E
<8>
Accession Number
641283020
Title
Hepatoprotective effect of semaglutide in the GAN diet-induced obese and biopsy-
confirmed mouse model of NASH with advanced fibrosis and HCC development.
Source
Hepatology International. Conference: 32nd Annual Conference of Asian Pacific
Association for the Study of the Liver. Taipei Taiwan (Republic of China).
17(Supplement 1) (pp S163-S164), 2023. Date of Publication: April 2023.
Author
Feigh M.; Nielsen M.H.; Mollerhoj M.B.; Pors S.; Vyberg M.; Hansen H.H.
Institution
(Feigh, Nielsen, Mollerhoj, Pors, Hansen) GubraDenmark
(Vyberg) Center for RNA Medicine, Denmark
Publisher
Springer
Subject Headings
adult
*advanced cancer
animal cell
animal experiment
animal model
animal tissue
blood biochemistry
C57BL 6 mouse
cancer growth
cancer staging
cell activation
cell proliferation
comparative effectiveness
conference abstract
controlled study
*diet-induced obesity
drug therapy
fibrogenesis
*fibrosis
hepatomegaly
*histology
histopathology
inflammation
liver biopsy
liver cell
liver histology
male
mouse
*mouse model
Nonalcoholic Fatty Liver Disease Activity Score
nonhuman
*obesity
pathologist
preclinical study
protein fingerprinting
steatosis
stem cell
alpha fetoprotein
aminotransferase
amylin
biological marker
cholesterol
endogenous compound
fat droplet
fructose
galectin 3
Ki 67 antigen
lipid
reticulin
*semaglutide
Drug Index Terms
alpha fetoprotein; aminotransferase; amylin; biological marker; cholesterol;
endogenous compound; fat droplet; fructose; galectin 3; Ki 67 antigen; lipid;
reticulin; *semaglutide
Other Index Terms
adult; *advanced cancer; animal cell; animal experiment; animal model; animal
tissue; blood biochemistry; C57BL 6 mouse; cancer growth; cancer staging; cell
activation; cell proliferation; comparative effectiveness; conference abstract;
controlled study; *diet-induced obesity; drug therapy; fibrogenesis; *fibrosis;
hepatomegaly; *histology; histopathology; inflammation; liver biopsy; liver cell;
liver cell carcinoma; liver histology; male; mouse; *mouse model; Nonalcoholic
Fatty Liver Disease Activity Score; nonhuman; *obesity; pathologist; preclinical
study; protein fingerprinting; steatosis; stem cell
Abstract
Background: The glucagon-like-receptor (GLP)-1 agonist semaglutide has
demonstrated therapeutic efficacy on clinical endpoints in a recent phase 2
clinical trial in patients with non-alcoholic steatohepatitis (NASH) (Newsome et
al. NEJM, 2021). The present study aimed to evaluate efficacy of semaglutide on
clinical NASH endpoints and progression of hepatocellular carcinoma (HCC) in the
GAN (Gubra-Amylin NASH) diet-induced obese (DIO) mouse model of NASH with advanced
fibrosis. Method(s): Male C57BL/6 J mice were fed the GAN diet high in fat,
fructose, and cholesterol for 52 weeks prior to study start. Only animals with
liver biopsy-confirmed NAFLD Activity Score (NAS >= 5) and advanced fibrosis (stage
F3) were included and stratified into treatment groups. DIO-NASH-HCC mice received
(SC, QD) vehicle (n = 16) or semaglutide (30 nmol/kg, n = 15) for 14 weeks.
Vehicledosed chow-fed C57BL/6 J mice (n = 9) served as lean healthy controls.
Untreated DIO-NASH-HCC mice (n = 10) were terminated at baseline. Tumor
histopathological classification was performed by an expert clinical pathologist.
Pre-to-post liver biopsy histopathology was performed for within-subject evaluation
of NAFLD Activity Score (NAS) and fibrosis stage. Additional endpoints included
blood biochemistry and quantitative liver histology. Result(s): Compared to
baseline, DIO-NASH-HCC mice demonstrated progressive HCC burden over the 14-week
study period. Tumors showed consistent architectural and cytologic features of HCC
with a marked loss of reticulin-stained fibers. Notably, semaglutide completely
prevented progression in HCC burden. In support, semaglutide reduced plasma levels
of the HCC biomarker alfa-fetoprotein. Concurrently, semaglutide improved hallmarks
of NASH, including transaminases, hepatomegaly and histopathological NAS (>= 2
point) without improving fibrosis stage. In agreement, semaglutide reduced
quantitative histological markers of steatosis (lipids, hepatocytes with lipid
droplets), inflammation (number of inflammatory foci, galectin- 3), fibrogenesis
(alpha-SMA), proliferation (Ki67) and progenitor cell activation (CK19).
Conclusion(s): This is the first study to demonstrate that semaglutide improves
both clinical histopathological endpoints for NAFLD Activity Score and HCC burden
in a preclinical translational mouse model of NASH-driven HCC. This highlights the
suitability of GAN DIO-NASH-HCC mice for profiling novel drug therapies targeting
NASH with advanced fibrosis and HCC.
S164&date=2023&title=Hepatology+International&atitle=Hepatoprotective+effect+of+sem
aglutide+in+the+GAN+diet-induced+obese+and+biopsy-
confirmed+mouse+model+of+NASH+with+advanced+fibrosis+and+HCC+development&aulast=Fei
gh&pid=%3Cauthor%3EFeigh+M.%3BNielsen+M.H.%3BMollerhoj+M.B.%3BPors+S.%3BVyberg+M.
%3BHansen+H.H.%3C%2Fauthor%3E%3CAN%3E641283020%3C%2FAN%3E%3CDT
<9>
Accession Number
2020537724
PMID
Title
Gender Dimorphism in Hepatic Carcinogenesis-Related Gene Expression Associated
with Obesity as a Low-Grade Chronic Inflammatory Disease.
Source
International Journal of Molecular Sciences. 23(23) (no pagination), 2022.
Article Number: 15002. Date of Publication: December 2022.
Author
Izquierdo A.G.; Carreira M.C.; Rodriguez-Carnero G.; Perez-Lois R.; Seoane L.M.;
Casanueva F.F.; Crujeiras A.B.
Author NameID
Crujeiras, Ana B.; ORCID: https://orcid.org/0000-0003-4392-0301
Seoane, Luisa M.; ORCID: https://orcid.org/0000-0003-1004-9898
Casanueva, Felipe F.; ORCID: https://orcid.org/0000-0002-9052-8161
Institution
(Izquierdo, Rodriguez-Carnero, Crujeiras) Epigenomics in Endocrinology and
Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago
de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela
(CHUS/SERGAS), Santiago de Compostela 15706, Spain
(Carreira, Seoane, Casanueva, Crujeiras) CIBER Fisiopatologia de la Obesidad y
Nutricion (CIBERobn), Madrid 28029, Spain
(Carreira, Casanueva) Molecular Endocrinology Group, Instituto de Investigacion
Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de
Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela 15706, Spain
(Rodriguez-Carnero) Division of Endocrinology and Nutrition, Complejo
Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Santiago de
Compostela 15706, Spain
(Perez-Lois, Seoane) Endocrine Physiopathology Group, Instituto de Investigacion
Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de
Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela 15706, Spain
Publisher
MDPI
Subject Headings
adult
animal cell
animal experiment
animal model
article
cancer susceptibility
*chronic inflammation
controlled study
diet-induced obesity
disease association
female
*gene expression level
genetic association
genetic susceptibility
human
leukocyte
*liver carcinogenesis
male
nonhuman
*obesity
oncogene
phenotype
rat
risk factor
*sex difference
statistical analysis
upregulation
baculoviral IAP repeat containing protein 5/ec [Endogenous Compound]
biological marker/ec [Endogenous Compound]
Drug Index Terms
baculoviral IAP repeat containing protein 5 / endogenous compound; biological
marker / endogenous compound
Other Index Terms
adult; animal cell; animal experiment; animal model; Article; cancer
susceptibility; *chronic inflammation; controlled study; diet-induced obesity;
disease association; female; *gene expression level; genetic association; genetic
susceptibility; human; leukocyte; *liver carcinogenesis; liver cell carcinoma;
male; nonhuman; *obesity; oncogene; phenotype; rat; risk factor; *sex difference;
statistical analysis; upregulation
Abstract
Non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) show
clear evidence of sexual dimorphism, with a significantly higher incidence in
males. Among the determining factors that could explain this sex-based difference,
the specific distribution of fat by sex has been suggested as a primary candidate,
since obesity is a relevant risk factor. In this context, obesity, considered a
low-grade chronic inflammatory pathology and responsible for the promotion of liver
disease, could lead to sexual dimorphism in the expression profile of genes related
to tumor development. When we compared the expression levels of genes associated
with the early stages of carcinogenesis in the liver between male and female diet-
induced obesity (DIO) rats, we observed that the expression pattern was similar in
obese male and female animals. Interestingly, the SURVIVIN/BIRC5 oncogene showed a
higher expression in male DIO rats than in female DIO and lean rats. This trend
related to sexual dimorphism was observed in leukocytes from patients with obesity,
although the difference was not statistically significant. In conclusion, this
study evidenced a similar pattern in the expression of most carcinogenesis-related
genes in the liver, except SUVIVIN/BIRC5, which could be a predictive biomarker of
liver carcinogenesis predisposition in male patients with obesity.Copyright © 2022
by the authors.
sid=OVID:embase&id=pmid:36499327&id=doi:10.3390%2Fijms232315002&issn=1661-
6596&isbn=&volume=23&issue=23&spage=15002&pages=&date=2022&title=International+Jour
nal+of+Molecular+Sciences&atitle=Gender+Dimorphism+in+Hepatic+Carcinogenesis-
Related+Gene+Expression+Associated+with+Obesity+as+a+Low-
Grade+Chronic+Inflammatory+Disease&aulast=Izquierdo&pid=%3Cauthor%3EIzquierdo+A.G.
%3BCarreira+M.C.%3BRodriguez-Carnero+G.%3BPerez-Lois+R.%3BSeoane+L.M.
%3BCasanueva+F.F.%3BCrujeiras+A.B.%3C%2Fauthor%3E%3CAN%3E2020537724%3C%2FAN%3E%3CDT
%3EArticle%3C%2FDT%3E
<10>
Accession Number
2019517201
PMID
Title
Geographical similarity and differences in the burden and genetic predisposition
of NAFLD.
Source
Hepatology. 77(4) (pp 1404-1427), 2023. Date of Publication: April 2023.
Author
Yip T.C.-F.; Vilar-Gomez E.; Petta S.; Yilmaz Y.; Wong G.L.-H.; Adams L.A.; De
Ledinghen V.; Sookoian S.; Wong V.W.-S.
Author NameID
Yip, Terry Cheuk-Fung; ORCID: https://orcid.org/0000-0002-1819-2464
Wong, Grace Lai-Hung; ORCID: https://orcid.org/0000-0002-2863-9389
Wong, Vincent Wai-Sun; ORCID: https://orcid.org/0000-0003-2215-9410
Vilar-Gomez, Eduardo; ORCID: https://orcid.org/0000-0003-1435-4013
Petta, Salvatore; ORCID: https://orcid.org/0000-0002-0822-9673
Adams, Leon A.; ORCID: https://orcid.org/0000-0002-3968-7909
Sookoian, Silvia; ORCID: https://orcid.org/0000-0001-5929-5470
Institution
(Yip, Wong, Wong) Medical Data Analytics Center, Department of Medicine and
Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
(Yip, Wong, Wong) State Key Laboratory of Digestive Disease, The Chinese
University of Hong Kong, Hong Kong, Hong Kong
(Vilar-Gomez) Division of Gastroenterology and Hepatology, Department of
Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
(Petta) Section of Gastroenterology and Hepatology, Dipartimento Di Promozione
Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza
(PROMISE), University of Palermo, Palermo, Italy
(Yilmaz) Department of Gastroenterology, School of Medicine, Recep Tayyip Erdogan
University, Rize, Turkey
(Yilmaz) Liver Research Unit, Institute of Gastroenterology, Marmara University,
Istanbul, Turkey
(Adams) Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
(Adams) Medical School, University of Western Australia, Perth, Australia
(De Ledinghen) Hepatology Unit, Hopital Haut Leveque, Bordeaux University
Hospital, Bordeaux, France
(De Ledinghen) INSERM U1312, Bordeaux University, Bordeaux, France
(Sookoian) School of Medicine, Institute of Medical Research A Lanari, University
of Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
(Sookoian) Department of Clinical and Molecular Hepatology, Institute of Medical
Research (IDIM), National Scientific and Technical Research Council (CONICET),
University of Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
Publisher
Wolters Kluwer Medknow Publications
Subject Headings
cancer growth
cancer patient
cancer prognosis
child
comorbidity
complication
decompensated liver cirrhosis
disease burden
economic aspect
ethnicity
genetic variability
health care system
human
liver cirrhosis
liver disease
liver fibrosis
mortality
outcome assessment
patient-reported outcome
quality of life
review
risk factor
Other Index Terms
cancer growth [m]; cancer patient [m]; cancer prognosis [m]; child [m];
comorbidity [m]; complication [m]; decompensated liver cirrhosis [m]; disease
burden [m]; economic aspect [m]; ethnicity [m]; genetic variability [m]; health
care system [m]; human [m]; liver cell carcinoma [m]; liver cirrhosis [m]; liver
disease [m]; liver fibrosis [m]; mortality [m]; non insulin dependent diabetes
mellitus [m]; *nonalcoholic fatty liver [m]; outcome assessment [m]; patient-
reported outcome [m]; quality of life [m]; review [m]; risk factor [m]
Abstract
NAFLD has become a major public health problem for more than 2 decades with a
growing prevalence in parallel with the epidemic of obesity and type 2 diabetes
(T2D). The disease burden of NAFLD differs across geographical regions and
ethnicities. Variations in prevalence of metabolic diseases, extent of urban-rural
divide, dietary habits, lifestyles, and the prevalence of NAFLD risk and protective
alleles can contribute to such differences. The rise in NAFLD has led to a
remarkable increase in the number of cases of cirrhosis, hepatocellular carcinoma,
hepatic decompensation, and liver-related mortality related to NAFLD. Moreover,
NAFLD is associated with multiple extrahepatic manifestations. Most of them are
risk factors for the progression of liver fibrosis and thus worsen the prognosis of
NAFLD. All these comorbidities and complications affect the quality of life in
subjects with NAFLD. Given the huge and growing size of the population with NAFLD,
it is expected that patients, healthcare systems, and the economy will suffer from
the ongoing burden related to NAFLD. In this review, we examine the disease burden
of NAFLD across geographical areas and ethnicities, together with the distribution
of some well-known genetic variants for NAFLD. We also describe some special
populations including patients with T2D, lean patients, the pediatric population,
and patients with concomitant liver diseases. We discuss extrahepatic outcomes,
patient-reported outcomes, and economic burden related to NAFLD.Copyright © 2023
John Wiley and Sons Inc.. All rights reserved.
sid=OVID:embase&id=pmid:36062393&id=doi:10.1002%2Fhep.32774&issn=0270-
9139&isbn=&volume=77&issue=4&spage=1404&pages=1404-
1427&date=2023&title=Hepatology&atitle=Geographical+similarity+and+differences+in+t
he+burden+and+genetic+predisposition+of+NAFLD&aulast=Yip&pid=%3Cauthor%3EYip+T.C.-
F.%3BVilar-Gomez+E.%3BPetta+S.%3BYilmaz+Y.%3BWong+G.L.-H.%3BAdams+L.A.
%3BDe+Ledinghen+V.%3BSookoian+S.%3BWong+V.W.-S.%3C%2Fauthor%3E%3CAN%3E2019517201%3C
%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<11>
Accession Number
2015703146
Title
Metabolic causes and consequences of nonalcoholic fatty liver disease (NAFLD).
Source
Metabolism Open. 12 (no pagination), 2021. Article Number: 100149. Date of
Publication: December 2021.
Author
Zarghamravanbakhsh P.; Frenkel M.; Poretsky L.
Institution
(Zarghamravanbakhsh, Poretsky) Division of Endocrinology, Department of Medicine,
Lenox Hill Hospital, Northwell Health, 110 East 59th St #8B, New York, NY 10022,
United States
(Frenkel, Poretsky) The Gerald J. Friedman Diabetes Institute, Northwell Health,
110 East 59th St #8B, New York, NY 10022, United States
Publisher
Elsevier Inc.
Subject Headings
all cause mortality
article
causal attribution
diet therapy
drug effect
human
insulin resistance
lipogenesis
liver cirrhosis
*metabolic disorder
*nonalcoholic fatty liver/dt [Drug Therapy]
nonalcoholic steatohepatitis/dt [Drug Therapy]
nonhuman
obesity/th [Therapy]
oxidative stress
prevalence
treatment outcome
treatment planning
glucagon like peptide 1 receptor agonist/dt [Drug Therapy]
Drug Index Terms
glucagon like peptide 1 receptor agonist / drug therapy
Other Index Terms
all cause mortality; Article; causal attribution; diet therapy; drug effect;
human; insulin resistance; lifestyle modification; lipogenesis; liver cirrhosis;
*metabolic disorder; non insulin dependent diabetes mellitus; *nonalcoholic fatty
liver / *drug therapy; nonalcoholic steatohepatitis / drug therapy; nonhuman;
obesity / therapy; oxidative stress; prevalence; treatment outcome; treatment
planning
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder
that was first described in 1980. It has been prevalent and on the rise for many
years and is associated with other metabolic disorders such as obesity and type 2
diabetes mellitus (T2DM). NAFLD can be best described as a metabolic dysfunction
that stems from insulin resistance-induced hepatic lipogenesis. This lipogenesis
increases oxidative stress and hepatic inflammation and is often potentiated by
genetic and gut microbiome dysfunction. As NAFLD progresses from simple steatosis
to non-alcoholic steatohepatitis (NASH) and to cirrhosis and hepatocellular
carcinoma (HCC), the odds of complications including cardiovascular disease (CVD),
chronic kidney disease (CKD), and overall mortality increase. The aim of this
review is to describe the metabolic causes and consequences of NAFLD while
examining the risks that each stage of NAFLD poses. In this review, the etiology of
"lean" NAFLD, the impact of obesity, T2DM, genetics, and microbiome dysbiosis on
NAFLD progression are all explored. This review will also discuss the core issue
behind the progression of NAFLD: insulin resistance (IR). Upon describing the
causes and consequences of NAFLD, the effectiveness of diet modification, lifestyle
changes, and glucagon-like peptide 1 receptor (GLP-1) agonists to retard NAFLD
progression and stem the rate of complications is examined.Copyright © 2021
Northwell Health
sid=OVID:embase&id=pmid:&id=doi:10.1016%2Fj.metop.2021.100149&issn=2589-
9368&isbn=&volume=12&issue=&spage=100149&pages=&date=2021&title=Metabolism+Open&ati
tle=Metabolic+causes+and+consequences+of+nonalcoholic+fatty+liver+disease+%28NAFLD
%29&aulast=Zarghamravanbakhsh&pid=%3Cauthor%3EZarghamravanbakhsh+P.%3BFrenkel+M.
%3BPoretsky+L.%3C%2Fauthor%3E%3CAN%3E2015703146%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT
%3E
<12>
Accession Number
640306307
PMID
Title
A diet-induced murine model for non-alcoholic fatty liver disease with obesity
and insulin resistance that rapidly develops steatohepatitis and fibrosis.
Source
Laboratory investigation; a journal of technical methods and pathology. 102(10)
(pp 1150-1157), 2022. Date of Publication: 01 Oct 2022.
Author
Sakuma T.; Nakamura M.; Chiba T.; Iwanaga T.; Kan M.; Kojima R.; Ao J.; Ma Y.;
Unozawa H.; Fujita N.; Kanayama K.; Kanzaki H.; Koroki K.; Kobayashi K.; Nakagawa
R.; Kanogawa N.; Kiyono S.; Kondo T.; Saito T.; Ogasawara S.; Nakamoto S.; Muroyama
R.; Kato J.; Kishimoto T.; Kato N.
Institution
(Sakuma, Nakamura, Chiba, Iwanaga, Kan, Kojima, Ao, Ma, Unozawa, Fujita,
Kanayama, Kanzaki, Koroki, Nakagawa, Kanogawa, Kiyono, Kondo, Saito, Nakamoto,
Kato, Kato) Department of Gastroenterology, Chiba University, Graduate School of
Medicine, Chiba 260-8677, Japan
(Kobayashi, Ogasawara) Department of Gastroenterology, Chiba University, Graduate
School of Medicine, 260-8677, Chiba, Japan; Translational Research and Development
Center, Chiba University Hospital, 260-8677, Chiba, Japan
(Muroyama) Department of Molecular Virology, Chiba University, Graduate School of
(Kishimoto) Department of Molecular Pathology, Chiba University, Graduate School
of Medicine, Chiba 260-8677, Japan
Publisher
NLM (Medline)
Subject Headings
adverse event
animal
C57BL mouse
complication
disease model
fibrosis
*insulin resistance
lipid diet
liver
liver cirrhosis/et [Etiology]
metabolism
mouse
*non insulin dependent diabetes mellitus
obesity
cholesterol
Drug Index Terms
cholesterol
Other Index Terms
adverse event; animal; C57BL mouse; complication; disease model; fibrosis;
*insulin resistance; lipid diet; liver; liver cirrhosis / etiology; metabolism;
mouse; *non insulin dependent diabetes mellitus; *nonalcoholic fatty liver; obesity
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic
liver disease worldwide. Patients with NAFLD often suffer steatohepatitis, which
can progress to cirrhosis and hepatocellular carcinoma. The presence of visceral
obesity or type 2 diabetes mellitus (T2DM) is a major risk factor and potential
therapeutic target for NAFLD. The establishment of animal models with these
metabolic comorbidities and with the rapid progression of the disease is needed for
developing treatments for NAFLD but remains to be archived. In the present study,
KK-Ay mice, widely used as T2DM models, or C57BL6 mice were fed a high-fat, high-
fructose, and high-cholesterol diet supplemented with cholic acid (NAFLD diet). The
KK-Ay mice fed a NAFLD diet exhibited remarkable obesity and insulin resistance. A
prominent accumulation of triglycerides and cholesterol in the liver was observed
at 4 weeks. These mice developed steatohepatitis at 4 weeks and fibrosis at 12
weeks. In contrast, C57BL6 mice fed a NAFLD diet remained lean, although they still
developed steatohepatitis and fibrosis. In summary, we established a diet-induced
murine NAFLD model with the rapid development of steatohepatitis and fibrosis,
bearing obesity and insulin resistance. This model could be useful as preclinical
models for drug development of NAFLD.Copyright © 2022 United States & Canadian
Academy of Pathology. Published by Elsevier Inc. All rights reserved.
sid=OVID:embase&id=pmid:36775355&id=doi:10.1038%2Fs41374-022-00807-6&issn=1530-
1157&date=2022&title=Laboratory+investigation
%3B+a+journal+of+technical+methods+and+pathology&atitle=A+diet-
induced+murine+model+for+non-
alcoholic+fatty+liver+disease+with+obesity+and+insulin+resistance+that+rapidly+deve
lops+steatohepatitis+and+fibrosis&aulast=Sakuma&pid=%3Cauthor%3ESakuma+T.
%3BNakamura+M.%3BChiba+T.%3BIwanaga+T.%3BKan+M.%3BKojima+R.%3BAo+J.%3BMa+Y.
%3BUnozawa+H.%3BFujita+N.%3BKanayama+K.%3BKanzaki+H.%3BKoroki+K.%3BKobayashi+K.
%3BNakagawa+R.%3BKanogawa+N.%3BKiyono+S.%3BKondo+T.%3BSaito+T.%3BOgasawara+S.
%3BNakamoto+S.%3BMuroyama+R.%3BKato+J.%3BKishimoto+T.%3BKato+N.%3C%2Fauthor%3E%3CAN
<13>
Accession Number
2020450603
PMID
Title
Epidemiology and prevalence of lean nonalcoholic fatty liver disease and
associated cirrhosis, hepatocellular carcinoma, and cardiovascular outcomes in the
United States: a population-based study and review of literature.
Source
Journal of Gastroenterology and Hepatology (Australia). 38(2) (pp 269-273), 2023.
Date of Publication: February 2023.
Author
Almomani A.; Kumar P.; Onwuzo S.; Boustany A.; Krishtopaytis E.; Hitawala A.;
Alshaikh D.; Albakri A.; Hussein L.; Hussein E.; Asaad I.
Author NameID
Almomani, Ashraf; ORCID: https://orcid.org/0000-0003-1648-0005
Boustany, Antoine; ORCID: https://orcid.org/0000-0002-4661-1443
Hussein, Leen; ORCID: https://orcid.org/0000-0002-3428-9282
Institution
(Almomani, Kumar, Onwuzo, Boustany, Krishtopaytis, Asaad) Cleveland Clinic
Foundation, Cleveland, OH, United States
(Hitawala) National Institute of Health, Bethesda, MD, United States
(Alshaikh) Mutah University, Al-Karak, Jordan
(Albakri) Jordanian Royal Medical Services, Amman, Jordan
(Hussein, Hussein) Al Andalus University for Medical Sciences, Tartus, Syrian
Arab Republic
Publisher
John Wiley and Sons Inc
Subject Headings
acute coronary syndrome
adult
aged
article
Asian
cancer risk
cardiovascular risk
clinical outcome
*coronary artery disease
*disease association
esophagus varices
female
human
*liver cell carcinoma
*liver cirrhosis
male
*prevalence
risk factor
smoking
Systematized Nomenclature of Medicine
United States
acetylsalicylic acid
hydroxymethylglutaryl coenzyme A reductase inhibitor
data analysis software
Device Index Terms
Drug Index Terms
acetylsalicylic acid; hydroxymethylglutaryl coenzyme A reductase inhibitor
Other Index Terms
acute coronary syndrome; adult; aged; Article; Asian; cancer risk; cardiovascular
risk; clinical outcome; *coronary artery disease; *disease association; esophagus
varices; female; human; *liver cell carcinoma; *liver cirrhosis; male; metabolic
syndrome X; *nonalcoholic fatty liver / *epidemiology; *prevalence; risk factor;
smoking; Systematized Nomenclature of Medicine; United States
Abstract
Backgrounds: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and
metabolic syndrome conditions. However, a subset of NAFLD patients express a normal
or low body mass index (lean NAFLD [L-NAFLD]). Our aim is to compare the prevalence
of L-NAFLD to the obesity-associated NAFLD in the United States by assessing
prevalence, potential risk factors, liver-related complications, and coronary
artery disease outcomes. Methodology: A multicenter database (Explorys Inc.) of >70
million patients across the United States was screened. A cohort of patients with
"nonalcoholic fatty liver" between 1999 and 2021 was identified. Two sub-cohorts of
NAFLD patients were identified: those with a body mass index (BMI) < 25 kg/m2 (L-
NAFLD) and those with a BMI > 30 kg/m2 (obesity-associated NAFLD). We excluded
patients with age <18 and those who have viral hepatitis, hemochromatosis, Wilson's
disease, biliary cirrhosis, alcoholic liver disease, cystic fibrosis, alpha-1-
antitrypsin deficiency, and autoimmune hepatitis. Multivariate analysis was
performed to adjust for confounders. Result(s): 68 892 260 individuals were
screened. NAFLD prevalence was four per 100 000, and L-NAFLD prevalence was 0.6 per
100 000. Compared with those without, patients with L-NAFLD tended to be older (OR
2.16), females (OR 1.28), and smokers (OR 4.67) and of Asian race (OR 2.12). L-
NAFLD patients were more likely to have acute coronary syndromes (OR 30.00) and
metabolic syndrome (OR 2.31) despite the normal/low BMI. Esophageal varices and
hepatocellular carcinoma risks were high in both cirrhosis patients. Conclusion(s):
This is the largest study to assess L-NAFLD prevalence in the United States. L-
NAFLD are at a significantly higher risk for acute coronary syndromes, esophageal
varices, and hepatocellular carcinoma.Copyright © 2022 The Authors. Journal of
Gastroenterology and Hepatology published by Journal of Gastroenterology and
Hepatology Foundation and John Wiley & Sons Australia, Ltd.
sid=OVID:embase&id=pmid:36328950&id=doi:10.1111%2Fjgh.16049&issn=0815-
273&date=2023&title=Journal+of+Gastroenterology+and+Hepatology+%28Australia
%29&atitle=Epidemiology+and+prevalence+of+lean+nonalcoholic+fatty+liver+disease+and
+associated+cirrhosis%2C+hepatocellular+carcinoma
%2C+and+cardiovascular+outcomes+in+the+United+States%3A+a+population-
based+study+and+review+of+literature&aulast=Almomani&pid=%3Cauthor%3EAlmomani+A.
%3BKumar+P.%3BOnwuzo+S.%3BBoustany+A.%3BKrishtopaytis+E.%3BHitawala+A.
%3BAlshaikh+D.%3BAlbakri+A.%3BHussein+L.%3BHussein+E.%3BAsaad+I.%3C%2Fauthor%3E
%3CAN%3E2020450603%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<14>
Accession Number
633490149
PMID
Title
A review of non-alcoholic fatty liver disease in non-obese and lean individuals.
Source
Journal of gastroenterology and hepatology. (no pagination), 2020. Date of
Publication: 20 Nov 2020.
Author
Ahadi M.; Molooghi K.; Masoudifar N.; Beheshti Namdar A.; Vossoughinia H.;
Farzanehfar M.
Author NameID
Masoudifar, Negin; ORCID: https://orcid.org/0000-0002-7258-2981
Institution
(Ahadi, Beheshti Namdar, Vossoughinia, Farzanehfar) Department of
Gastroenterology and Hepatology, Mashhad University of Medical Sciences, Mashhad,
Iran, Islamic Republic of
(Molooghi, Masoudifar) School of Medicine, Mashhad University of Medical
Sciences, Mashhad, Iran, Islamic Republic of
Publisher
NLM (Medline)
Subject Headings
adult
*body mass
*body weight loss
controlled study
fructose intake
gene frequency
genetic association
genetic polymorphism
human
intraperitoneal fat
lifestyle
*obesity
physical activity
prevalence
protein domain
review
endogenous compound
insulin
phospholipase
triacylglycerol
Drug Index Terms
endogenous compound [m]; insulin [m]; phospholipase [m]; triacylglycerol [m]
Other Index Terms
adult [m]; *body mass [m]; *body weight loss [m]; controlled study [m]; fructose
intake [m]; gene frequency [m]; genetic association [m]; genetic polymorphism [m];
genetic susceptibility [m]; human [m]; intraperitoneal fat [m]; lifestyle [m];
*nonalcoholic fatty liver [m]; *obesity [m]; physical activity [m]; prevalence [m];
protein domain [m]; review [m]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of
hepatic disorders. It represents a wide range of chronic liver diseases in patients
with no history of significant alcohol consumption, starting with simple steatosis
and progressing towards non-alcoholic steatohepatitis (NASH), cirrhosis, and
ultimately hepatocellular carcinoma. NAFLD is usually associated with type 2
diabetes mellitus, dyslipidemia, metabolic syndrome and obesity. This disease has
mostly been studied in obese individuals; however, it has been widely reported and
studied among the lean/non-obese population in recent years. The pathogenesis of
NAFLD in non-obese patients is associated with various genetic predispositions,
particularly a patatin-like phospholipase domain-containing protein 3 (PNPLA 3) G
allele polymorphism, which results in the accumulation of triglyceride in the liver
and resistance to insulin. Additionally, dietary factors such as high fructose
consumption seem to play a substantial role in the pathology of non-obese NAFLD.
Although there is not enough evidence on the treatment of NAFLD in non-obese
patients, the standard approach is to advise altering one's lifestyle in order to
diminish visceral adiposity. Dietary modification, weight loss and increased
physical activity are highly recommended. We aimed to review and summarize the
existing information on the prevalence, pathogenesis, genetic predispositions,
diagnosis and treatment of NAFLD in non-obese patients according to the latest
literature.Copyright This article is protected by copyright. All rights reserved.
1746&isbn=&volume=36&issue=6&spage=1497&pages=&date=2020&title=Journal+of+gastroent
erology+and+hepatology&atitle=A+review+of+non-alcoholic+fatty+liver+disease+in+non-
obese+and+lean+individuals&aulast=Ahadi&pid=%3Cauthor%3EAhadi+M.%3BMolooghi+K.
%3BMasoudifar+N.%3BBeheshti+Namdar+A.%3BVossoughinia+H.%3BFarzanehfar+M.%3C
%2Fauthor%3E%3CAN%3E633490149%3C%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<15>
Accession Number
631593861
PMID
Title
Metabolic syndrome is not uncommon among lean non-alcoholic fatty liver disease
patients as compared with those with obesity.
Source
Indian journal of gastroenterology : official journal of the Indian Society of
Gastroenterology. (no pagination), 2020. Date of Publication: 20 Apr 2020.
Author
Sinha N.; Mukhopadhyay S.; Sau M.
Institution
(Sinha) Community Medicine, Midnapore Medical College, Midnapore 721 101, India
(Mukhopadhyay) Department of General Medicine, Vivekananda Institute of Medical
Sciences, Kolkata 700 026, India
(Sau) Community Medicine, Midnapore Medical College, Midnapore 721 101, India
Publisher
NLM (Medline)
Subject Headings
adult
article
body mass
*cancer patient
cardiovascular risk
clinical feature
controlled study
cross-sectional study
*diabetes mellitus
diastolic blood pressure
echography
female
glucose blood level
human
human tissue
India
International Diabetes Federation
*liver cirrhosis
male
*obesity
prevalence
risk assessment
systolic blood pressure
teaching hospital
tertiary health care
Other Index Terms
adult [m]; article [m]; body mass [m]; *cancer patient [m]; cardiovascular risk
[m]; clinical feature [m]; controlled study [m]; cross-sectional study [m];
*diabetes mellitus [m]; diastolic blood pressure [m]; echography [m]; female [m];
glucose blood level [m]; human [m]; human tissue [m]; India [m]; International
Diabetes Federation [m]; *liver cell carcinoma [m]; *liver cirrhosis [m]; major
clinical study [m]; male [m]; *metabolic syndrome X [m]; *nonalcoholic fatty liver
[m]; *obesity [m]; prevalence [m]; risk assessment [m]; systolic blood pressure
[m]; teaching hospital [m]; tertiary health care [m]; triacylglycerol blood level
[m]
Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity,
which is known to be associated with metabolic syndrome (MS). However, the risk
factors for NAFLD in absence of obesity (leanness) is not well-studied. This study
aimed to investigate and compare the clinical characteristics, metabolic
associations, and cardiovascular risk factors among patients having NAFLD with
(body mass index [BMI] >=23 kg/m2) or without obesity (BMI <23 kg/m2). METHOD(S):
The cross-sectional study was conducted among the outdoor and indoor patients
diagnosed as NAFLD by ultrasonography in a tertiary care teaching hospital in
eastern India. Relevant anthropometric measurements, laboratory investigations, and
imaging were performed. Metabolic syndrome was classified by the "International
Diabetes Federation, 2005" criteria. RESULT(S): Among 120 NAFLD patients, 37
(30.8%) were lean, while 83 (69.2%) were obese. The components of MS such as
systolic blood pressure (lean, 138.0+/-17.6 mmHg; obese, 137.9+/-15.3 mmHg),
diastolic blood pressure (lean, 88.9+/-6.5 mmHg; obese, 87.3+/-6.1 mmHg), fasting
blood sugar (lean, 127.8+/-30.8 mg/dL; obese, 135.1+/-29.5 mg/dL), and serum
triglyceride (lean, 170.5+/-34.2 mg/dL; obese, 186.4+/-43.8 mg/dL) were comparable
among patients with obese and lean NAFLD and were more often abnormal among both
the groups of NAFLD as compared with controls. CONCLUSION(S): The overall
prevalence of MS among NAFLD study population was 64.2%. Lean NAFLD was also
associated with the component of MS like obese NAFLD.
0711&isbn=&volume=39&issue=1&spage=75&pages=&date=2020&title=Indian+journal+of+gast
roenterology+
%3A+official+journal+of+the+Indian+Society+of+Gastroenterology&atitle=Metabolic+syn
drome+is+not+uncommon+among+lean+non-
alcoholic+fatty+liver+disease+patients+as+compared+with+those+with+obesity&aulast=S
inha&pid=%3Cauthor%3ESinha+N.%3BMukhopadhyay+S.%3BSau+M.%3C%2Fauthor%3E%3CAN
<16>
Accession Number
628075898
PMID
Title
High Risk of Fatty Liver Disease Amplifies the Alanine Transaminase-Lowering
effect of a HSD17B13 Variant.
Source
Hepatology (Baltimore, Md.). (no pagination), 2019. Date of Publication: 03 Jun
2019.
Author
Gellert-Kristensen H.; Nordestgaard B.G.; Tybjaerg-Hansen A.; Stender S.
Institution
(Gellert-Kristensen, Tybjaerg-Hansen, Stender) Department of Clinical
Biochemistry, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health
and Medical Sciences, University of Copenhagen, Denmark
(Nordestgaard) Department of Clinical Biochemistry, Copenhagen University
Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen,
Denmark
(Nordestgaard, Tybjaerg-Hansen) Copenhagen General Population Study, Herlev and
Gentofte Hospital, Copenhagen University Hospitals and Faculty of Health and
Medical Sciences, University of Copenhagen, Denmark
(Nordestgaard, Tybjaerg-Hansen) Copenhagen City Heart Study, Bispebjerg and
Frederiksberg Hospital, Copenhagen University Hospitals and Faculty of Health and
Medical Sciences, University of Copenhagen, Denmark
Publisher
NLM (Medline)
Subject Headings
adult
alcohol consumption
article
cancer patient
chronic liver disease
controlled study
*fatty liver
female
gene amplification
gene expression
gene frequency
genetic association
*genetic polymorphism
genetic risk
homozygote
human
human tissue
*liver cirrhosis
male
mortality
*obesity
plasma
population
protein blood level
protein expression
*protein function
*alanine aminotransferase
*alcohol
endogenous compound
Drug Index Terms
*alanine aminotransferase [m]; *alcohol [m]; endogenous compound [m]
Other Index Terms
adult [m]; alcohol consumption [m]; article [m]; cancer patient [m]; chronic
liver disease [m]; controlled study [m]; *fatty liver [m]; female [m]; gene
amplification [m]; gene expression [m]; gene frequency [m]; genetic association
[m]; *genetic polymorphism [m]; genetic risk [m]; genetic susceptibility [m];
homozygote [m]; human [m]; human tissue [m]; liver cell carcinoma [m]; *liver
cirrhosis [m]; major clinical study [m]; male [m]; mortality [m]; *obesity [m];
plasma [m]; population [m]; protein blood level [m]; protein expression [m];
*protein function [m]
Abstract
A common loss-of-function variant in HSD17B13 (rs72613567:TA) was recently found
to protect from chronic liver disease. Whether the variant confers protection from
specific risk factors for liver disease is unclear. We tested the association of
rs72613567 with plasma levels of alanine transaminase (ALT) and clinical liver
disease and mortality in 111,612 individuals from the Danish general population,
including 497 with cirrhosis and 113 with hepatocellular carcinoma. HSD17B13
rs72613567:TA was associated with stepwise lower levels of plasma ALT of up to 1.3
U/L in TA/TA homozygotes versus T/T homozygotes. For each TA-allele, the risk of
cirrhosis and hepatocellular carcinoma was reduced by 15% and 28%, respectively. In
prospective analyses, the TA-allele was associated with up to 33% lower rates of
liver-related mortality in the general population, and with up to 49% reduced
liver-related mortality in patients with cirrhosis. The ALT-lowering effect of
rs72613567:TA was amplified by increasing adiposity, alcohol consumption, and
genetic risk of fatty liver disease. The TA-allele was associated with only
marginally lower ALT in lean nondrinkers with low genetic risk of hepatic
steatosis. In contrast, compared to T/T homozygotes, TA/TA homozygotes had 12% to
18% lower plasma ALT among the most obese, in heavy drinkers, and in individuals
carrying three or four steatogenic alleles in PNPLA3 and TM6SF2. CONCLUSION(S):
High risk of fatty liver disease amplifies the ALT-lowering effect of HSD17B13
rs72613567:TA in the Danish general population. This article is protected by
copyright. All rights reserved.
3350&isbn=&volume=71&issue=1&spage=56&pages=&date=2019&title=Hepatology+
%28Baltimore%2C+Md.
%29&atitle=High+Risk+of+Fatty+Liver+Disease+Amplifies+the+Alanine+Transaminase-
Lowering+effect+of+a+HSD17B13+Variant&aulast=Gellert-Kristensen&pid=%3Cauthor
%3EGellert-Kristensen+H.%3BNordestgaard+B.G.%3BTybjaerg-Hansen+A.%3BStender+S.%3C
%2Fauthor%3E%3CAN%3E628075898%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<17>
Accession Number
2021679665
Title
Lean individual's non-alcoholic fatty liver disease: a review article.
Source
Tehran University Medical Journal. 80(8) (pp 422-433), 2022. Date of Publication:
September 2022.
Author
Daryani N.E.; Pashaei M.R.
Institution
(Daryani) Department of Gastroenterology, Imam Khomeini Hospital Complex, School
of Medicine, Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic
of
(Pashaei) Patient Safety Research Center, Clinical Research Institute, Urmia
University of Medical Sciences, Urmia, Iran, Islamic Republic of
(Pashaei) Department of Internal Medicine, School of Medicine, Urmia University
of Medical Science, Urmia, Iran, Islamic Republic of
Publisher
Tehran University of Medical Sciences
Subject Headings
abdominal fat
body weight loss
diagnostic procedure
diet
disease burden
epigenetics
fatty liver
human
human cell
imaging
incidence
laboratory test
liver biopsy
liver cell
liver cirrhosis
morbidity
mortality
obesity
pathogenesis
pathophysiology
physical activity
population
prevalence
prognosis
review
alpha tocopherol
pioglitazone
Drug Index Terms
alpha tocopherol; pioglitazone
Other Index Terms
abdominal fat; body weight loss; chronic liver disease; diagnostic procedure;
diet; disease burden; epigenetics; fatty liver; genetic susceptibility; human;
human cell; imaging; incidence; laboratory test; lifestyle modification; liver
biopsy; liver cell; liver cell carcinoma; liver cirrhosis; metabolic syndrome X;
morbidity; mortality; non insulin dependent diabetes mellitus; *nonalcoholic fatty
liver; nonalcoholic steatohepatitis; obesity; pathogenesis; pathophysiology;
physical activity; population; prevalence; prognosis; Review
Abstract
Nonalcoholic fatty liver disease (NAFLD) is defined by steatosis in more than 5%
of liver cells, in the absence of a secondary cause such as drugs, alcohol, or
other causes. The incidence of NAFLD is increasing every day; almost a quarter of
the world's adult population is affected by this disease. The burden of NAFLD is
affected by the epidemics of obesity and type 2 diabetes (T2DM), and therefore, we
do not expect the prevalence of this disease to decrease in the future. The world
is now in the process of passing on health to non-chronic diseases, like NAFLD. The
most common cause of chronic liver disease worldwide is non-alcoholic fatty liver
disease. About 25 percent of the world's population is affected by the disease, and
it ranges from simple steatosis to cirrhosis. 1 in 4 individuals with NAFLD is a
person with non-alcoholic steatohepatitis, which is associated with complications
and significant mortality and morbidity due to complications such as liver
cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is
closely related to metabolic syndrome, and it can be said that the liver is an
integral part of obesity. Diagnostic methods for this disease include laboratory
tests, imaging studies and liver biopsy. Although NAFLD is observed predominantly
in obese persons or type 2 diabetes, an estimated 7% to 20% of people with NAFLD
have lean body habitus. Recent studies have shown that fatty liver can occur in
lean individuals, even without abdominal and visceral fat. Fatty liver in lean
people (Lean NAFLD) is a relatively new concept that has attracted many people to
find the differences between lean and obese people. The pathophysiological
mechanisms of lean NAFLD are still poorly understood. Studies have shown that NAFLD
without obesity is more closely related to factors such as environmental, genetic
susceptibility, and epigenetic regulation. In addition to lifestyle modifications
such as weight loss, diet and physical activity, only a few NAFLD-specific drug
treatment options such as vitamin E and pioglitazone are considered. This article
discusses the pathogenesis of fatty liver in lean individuals, its treatment,
prognosis, and its relationship with metabolic syndrome.Copyright © 2022 Daryani et
al. Published by Tehran University of Medical Sciences.
T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emexa&AN=2021679665
sid=OVID:embase&id=pmid:&id=doi:&issn=1683-
433&date=2022&title=Tehran+University+Medical+Journal&atitle=
%3A&aulast=Daryani&pid=%3Cauthor%3EDaryani+N.E.%3BPashaei+M.R.%3C%2Fauthor%3E%3CAN
<18>
Accession Number
2018790696
Title
Effect of metabolic dysfunction-associated fatty liver disease on liver cancer
risk in a population with chronic hepatitis B virus infection: A nationwide study.
Source
Hepatology Research. 52(12) (pp 975-984), 2022. Date of Publication: December
2022.
Author
Yun B.; Ahn S.H.; Oh J.; Yoon J.-H.; Kim B.K.
Institution
(Yun, Yoon) Department of Preventive Medicine, Yonsei University College of
Medicine, Seoul, South Korea
(Ahn, Kim) Department of Internal Medicine, Yonsei University College of
Medicine, Seoul, South Korea
(Ahn, Kim) Institute of Gastroenterology, Yonsei University College of Medicine,
Seoul, South Korea
(Ahn, Kim) Yonsei Liver Center, Severance Hospital, Yonsei University Health
System, Seoul, South Korea
(Oh) Department of Public Health, Graduate School, Yonsei University, Seoul,
South Korea
(Yoon) Department of Occupational Health, Department of Preventive Medicine,
Yonsei University College of Medicine, Seoul, South Korea
Publisher
Subject Headings
adult
alcohol consumption
all cause mortality
article
body mass
*cancer risk
*chronic hepatitis B
cohort analysis
diabetes mellitus
dyslipidemia
female
human
hypertension
ICD-10
*liver cancer
liver cirrhosis
male
medical examination
*metabolic fatty liver
metabolism
obesity
outcome assessment
physical activity
retrospective study
smoking
virus infection
waist circumference
alanine aminotransferase/ec [Endogenous Compound]
antidiabetic agent
antihypertensive agent
antilipemic agent
aspartate aminotransferase/ec [Endogenous Compound]
gamma glutamyltransferase/ec [Endogenous Compound]
Drug Index Terms
alanine aminotransferase / endogenous compound; antidiabetic agent;
antihypertensive agent; antilipemic agent; aspartate aminotransferase / endogenous
compound; gamma glutamyltransferase / endogenous compound; triacylglycerol /
endogenous compound
Other Index Terms
adult; alcohol consumption; all cause mortality; Article; body mass; *cancer
risk; *chronic hepatitis B; cohort analysis; diabetes mellitus; dyslipidemia;
female; human; hypertension; ICD-10; *liver cancer; liver cirrhosis; major clinical
study; male; medical examination; *metabolic fatty liver; metabolism; obesity;
outcome assessment; physical activity; retrospective study; smoking; virus
infection; waist circumference
Abstract
Background: The association between metabolic dysfunction-associated fatty liver
disease (MAFLD) and hepatocellular carcinoma (HCC) lacks clinical validation in at-
risk populations. We assessed this relationship among chronic hepatitis B (CHB)
patients. Method(s): Data was collected from the National Health Insurance System
database in South Korea. Chronic hepatitis B patients aged over 40 years receiving
health examinations between 2011 and 2012 were recruited. The primary outcome was
HCC. Metabolic dysfunction-associated fatty liver disease was defined as hepatic
steatosis in combination with at least one of the following: (i) overweight, (ii)
diabetes, or (iii) lean/normal weight with two or more metabolic components.
Multivariable Cox regression analysis was used to estimate adjusted hazard ratios
(aHRs). Result(s): Of 197 346 participants, 66 149 had MAFLD; 19 149, 44 475, and
2525 fulfilled diabetes (regardless of overweight), overweight alone, and
lean/normal weight with two or more metabolic components, respectively. During
follow-up (median 7 years), 13 771 developed HCC. Metabolic dysfunction-associated
fatty liver disease was independently associated with increased risk of HCC, with
aHR of 1.36 (p < 0.001). Propensity score matching confirmed the same phenomena,
with aHR of 1.37 (p < 0.001). Furthermore, when stratified by liver cirrhosis
and/or antiviral therapy, independent significances of MAFLD for HCC risk were
maintained (all p < 0.001). Compared with the persistent non-MAFLD subgroup during
the entire follow-up, diagnosis of MAFLD from at least one health examination
significantly increased HCC risk with aHRs of 1.41, 1.37, and 1.14 among subgroups
with persistent MAFLD, MAFLD to non-MAFLD, and non-MAFLD to MAFLD, respectively
(all p < 0.05). Conclusion(s): Metabolic dysfunction-associated fatty liver disease
consistently increases HCC risk among CHB patients. Further studies are needed to
develop an effective preventive strategy through control of metabolic
health.Copyright © 2022 The Japan Society of Hepatology.
sid=OVID:embase&id=pmid:&id=doi:10.1111%2Fhepr.13830&issn=1386-
984&date=2022&title=Hepatology+Research&atitle=Effect+of+metabolic+dysfunction-
associated+fatty+liver+disease+on+liver+cancer+risk+in+a+population+with+chronic+he
patitis+B+virus+infection%3A+A+nationwide+study&aulast=Yun&pid=%3Cauthor%3EYun+B.
%3BAhn+S.H.%3BOh+J.%3BYoon+J.-H.%3BKim+B.K.%3C%2Fauthor%3E%3CAN%3E2018790696%3C
%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<19>
Accession Number
2020469048
PMID
Title
Differential methylation patterns in lean and obese non-alcoholic
steatohepatitis-associated hepatocellular carcinoma.
Source
BMC Cancer. 22(1) (no pagination), 2022. Article Number: 1276. Date of
Author
Hymel E.; Fisher K.W.; Farazi P.A.
Institution
(Hymel, Farazi) Department of Epidemiology, University of Nebraska Medical
Center, 984395 Nebraska Medical Center, Omaha, NE 68198-4395, United States
(Fisher) Department of Pathology and Microbiology, University of Nebraska Medical
Center, Omaha, NE, United States
Publisher
BioMed Central Ltd
Subject Headings
animal experiment
animal model
animal tissue
article
bisulfite sequencing
cancer prognosis
cholesterol diet
controlled study
*DNA methylation
gene
high fat/high fructose diet
*lean body weight
lipid metabolism
liver cancer
liver carcinogenesis
*liver cell carcinoma/et [Etiology]
male
methylation
mouse
*nonalcoholic steatohepatitis
nonhuman
*obesity
Wnt signaling
choline
lipid/ec [Endogenous Compound]
Wnt protein/ec [Endogenous Compound]
CHCHD2 gene
FSCN1 gene
GJA8 gene
LDLRAP1 gene
LRRC8D gene
PNPLA6 gene
PSAPL1 gene
PTPRE gene
RNF217 gene
ZDHHC12 gene
Candidate Terms
CHCHD2 gene [other term]
FSCN1 gene [other term]
GJA8 gene [other term]
LDLRAP1 gene [other term]
LRRC8D gene [other term]
PNPLA6 gene [other term]
PSAPL1 gene [other term]
PTPRE gene [other term]
RNF217 gene [other term]
ZDHHC12 gene [other term]
Drug Index Terms
choline; lipid / endogenous compound; Wnt protein / endogenous compound
Other Index Terms
animal experiment; animal model; animal tissue; Article; bisulfite sequencing;
cancer prognosis; cholesterol diet; controlled study; *disease association; *DNA
methylation; gene; high fat/high fructose diet; *lean body weight; lipid
metabolism; liver cancer; liver carcinogenesis; *liver cell carcinoma / *etiology;
male; methylation; mouse; *nonalcoholic steatohepatitis; nonhuman; *obesity; Wnt
signaling
Abstract
Background: Nonalcoholic fatty liver disease affects about 24% of the world's
population and may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and
hepatocellular carcinoma (HCC). While more common in those that are obese, NASH-HCC
can develop in lean individuals. The mechanisms by which HCC develops and the role
of epigenetic changes in the context of obesity and normal weight are not well
understood. Method(s): In this study, we used previously generated mouse models of
lean and obese HCC using a choline deficient/high trans-fat/fructose/cholesterol
diet and a choline supplemented/high trans-fat/fructose/cholesterol diet,
respectively, to evaluate methylation differences in HCC progression in lean versus
obese mice. Differentially methylated regions were determined using reduced
representation bisulfite sequencing. Result(s): A larger number of differentially
methylated regions (DMRs) were seen in NASH-HCC progression in the obese mice
compared to the non-obese mice. No overlap existed in the DMRs with the largest
methylation differences between the two models. In lean NASH-HCC, methylation
differences were seen in genes involved with cancer progression and prognosis
(including HCC), such as CHCHD2, FSCN1, and ZDHHC12, and lipid metabolism,
including PNPLA6 and LDLRAP1. In obese NASH- HCC, methylation differences were seen
in genes known to be associated with HCC, including RNF217, GJA8, PTPRE, PSAPL1,
and LRRC8D. Genes involved in Wnt-signaling pathways were enriched in
hypomethylated DMRs in the obese NASH-HCC. Conclusion(s): These data suggest that
differential methylation may play a role in hepatocarcinogenesis in lean versus
obese NASH. Hypomethylation of Wnt signaling pathway-related genes in obese mice
may drive progression of HCC, while progression of HCC in lean mice may be driven
through other signaling pathways, including lipid metabolism.Copyright © 2022, The
Author(s).
2407&isbn=&volume=22&issue=1&spage=1276&pages=&date=2022&title=BMC+Cancer&atitle=Di
fferential+methylation+patterns+in+lean+and+obese+non-alcoholic+steatohepatitis-
associated+hepatocellular+carcinoma&aulast=Hymel&pid=%3Cauthor%3EHymel+E.
%3BFisher+K.W.%3BFarazi+P.A.%3C%2Fauthor%3E%3CAN%3E2020469048%3C%2FAN%3E%3CDT
<20>
Accession Number
639720478
Title
HEPATOPROTECTIVE EFFECTS OF SEMAGLUTIDE IN THE GAN DIET-INDUCED OBESE AND BIOPSY-
CONFIRMED MOUSE MODEL OF NASH WITH ADVANCED FIBROSIS AND HEPATOCELLULAR CARCINOMA.
Source
Hepatology. Conference: Annual Meeting of the American Association for the Study
of Liver Diseases, AASLD 2022. Virtual. 76(Supplement 1) (pp S737-S738), 2022. Date
of Publication: October 2022.
Author
Nielsen M.H.; Mollerhoj M.B.; Oro D.; Madsen M.R.; Vyberg M.; Hansen H.H.; Feigh
M.
Institution
(Nielsen, Mollerhoj, Oro, Madsen, Hansen, Feigh) Gubra, Denmark
(Vyberg) Copenhagen University Hospital Hvidovre, Centre for RNA Medicine,
Aalborg University Copenhagen, Denmark
Publisher
John Wiley and Sons Inc.
Subject Headings
adult
*advanced cancer
animal cell
animal experiment
animal model
animal tissue
blood biochemistry
C57BL 6 mouse
cancer growth
cancer staging
carcinogenesis
cell activation
cell proliferation
conference abstract
controlled study
drug therapy
extracellular matrix
fibrogenesis
*fibrosis
gene expression
hepatomegaly
*histology
histopathology
human
inflammation
liver biopsy
liver cell
liver histology
male
mouse
*mouse model
nonhuman
*obesity
outcome assessment
pathologist
preclinical study
protein fingerprinting
RNA sequencing
steatosis
stem cell
aminotransferase
cholesterol
endogenous compound
fat droplet
fructose
galectin 3
Ki 67 antigen
lipid
reticulin
*semaglutide
Drug Index Terms
aminotransferase; cholesterol; endogenous compound; fat droplet; fructose;
galectin 3; Ki 67 antigen; lipid; reticulin; *semaglutide
Other Index Terms
adult; *advanced cancer; animal cell; animal experiment; animal model; animal
tissue; blood biochemistry; C57BL 6 mouse; cancer growth; cancer staging;
carcinogenesis; cell activation; cell proliferation; conference abstract;
controlled study; *diet-induced obesity; drug therapy; extracellular matrix;
fibrogenesis; *fibrosis; gene expression; hepatomegaly; *histology; histopathology;
human; inflammation; liver biopsy; liver cell; *liver cell carcinoma; liver
histology; male; mouse; *mouse model; Nonalcoholic Fatty Liver Disease Activity
Score; nonhuman; *obesity; outcome assessment; pathologist; preclinical study;
protein fingerprinting; RNA sequencing; steatosis; stem cell
Abstract
Background: The glucagon-like-receptor (GLP)-1 agonist semaglutide has
demonstrated therapeutic efficacy on clinical endpoints in a recent phase 2
clinical trial in patients with non-alcoholic steatohepatitis (NASH) (Newsome et
al. NEJM, 2021). The present study aimed to evaluate therapeutic efficacy of
semaglutide on clinical endpoints and outcome in the GAN (GubraAmylin NASH) diet-
induced obese (DIO) mouse model of NASH with advanced fibrosis and hepatocellular
carcinoma (HCC). Method(s): Male C57BL/6J mice were fed the GAN diet high in fat,
fructose, and cholesterol for extended 48weeks prior to study start. Only animals
with liver biopsy-confirmed NAFLD Activity Score (NAS >=5) and advanced fibrosis
(stage F3) were included and stratified into treatment groups. DIO-NASH-HCC mice
received (SC, QD) vehicle (n=16) or semaglutide (30 nmol/kg, n=15) for 14weeks.
Vehicle-dosed chow-fed C57BL/6J mice (n=9) served as lean healthy controls.
Untreated DIO-NASH-HCC mice (n=10) were terminated at baseline. Tumor
histopathological classification was performed by an expert clinical pathologist.
Pre-to-post liver biopsy histopathology was performed for within-subject evaluation
of NAFLD Activity Score (NAS) and fibrosis stage. Additional endpoints included
blood biochemistry, quantitative liver histology and whole-liver RNA sequencing.
Result(s): Compared to baseline, DIO-NASH-HCC mice demonstrated progressive HCC
burden over the 14-week study period. Tumors showed consistent architectural and
cytologic features of HCC with a marked loss of reticulin-stained fibers. Notably,
semaglutide completely prevented progression in HCC burden. Concurrently,
semaglutide improved hallmarks of NASH, including transaminases, hepatomegaly and
histopathological NAS (>=2 point) without improving fibrosis stage. In agreement,
semaglutide reduced quantitative histological markers of steatosis (lipids,
hepatocytes with lipid droplets), inflammation (number of inflammatory foci,
galectin-3), fibrogenesis (alpha-SMA), proliferation (Ki67) and progenitor cell
activation (CK19). Furthermore, hepatic gene expression signatures for semaglutide
demonstrated suppression of genes involved in inflammation, extracellular matrix
production and tumorigenesis. Conclusion(s): This is the first study to demonstrate
that semaglutide improves both clinical endpoints for NAFLD Activity Score and
outcome for HCC burden in a preclinical translational mouse model of NASH-driven
HCC. This highlights the suitability of GAN DIO-NASH-HCC mice for profiling novel
drug therapies targeting NASH with advanced fibrosis and HCC.
sid=OVID:embase&id=pmid:&id=doi:10.1002%2Fhep.32697&issn=1527-
S738&date=2022&title=Hepatology&atitle=HEPATOPROTECTIVE+EFFECTS+OF+SEMAGLUTIDE+IN+T
HE+GAN+DIET-INDUCED+OBESE+AND+BIOPSY-
CONFIRMED+MOUSE+MODEL+OF+NASH+WITH+ADVANCED+FIBROSIS+AND+HEPATOCELLULAR+CARCINOMA&a
ulast=Nielsen&pid=%3Cauthor%3ENielsen+M.H.%3BMollerhoj+M.B.%3BOro+D.%3BMadsen+M.R.
%3BVyberg+M.%3BHansen+H.H.%3BFeigh+M.%3C%2Fauthor%3E%3CAN%3E639720478%3C%2FAN%3E
%3CDT%3EConference+Abstract%3C%2FDT%3E
<21>
Accession Number
639719417
Title
DIFFERENTIAL METHYLATION PATTERNS IN LEAN AND OBESE NONALCOHOLIC STEATOHEPATITIS-
INDUCED HEPATOCELLULAR CARCINOMA IN THE MOUSE.
Source
Hepatology. Conference: Annual Meeting of the American Association for the Study
of Liver Diseases, AASLD 2022. Virtual. 76(Supplement 1) (pp S1361), 2022. Date of
Publication: October 2022.
Author
Hymel E.; Fisher K.; Farazi P.
Institution
(Hymel, Farazi) Epidemiology, University of Nebraska Medical Center, United
States
(Fisher) Pathology and Microbiology, University of Nebraska Medical Center,
United States
Publisher
Subject Headings
animal experiment
animal model
animal tissue
cancer growth
cancer prognosis
cancer staging
cholesterol diet
conference abstract
controlled study
*lipid metabolism
male
*methylation
mouse
mouse model
mouse mutant
nonhuman
*obesity
reduced representation bisulfite sequencing
signal transduction
Wnt signaling
endogenous compound
fascin
fructose
neurotoxic esterase
protein tyrosine phosphatase epsilon
Drug Index Terms
endogenous compound; fascin; fructose; neurotoxic esterase; protein tyrosine
phosphatase epsilon
Other Index Terms
animal experiment; animal model; animal tissue; cancer growth; cancer prognosis;
cancer staging; cholesterol diet; conference abstract; controlled study; genetic
susceptibility; *lipid metabolism; liver carcinogenesis; *liver cell carcinoma;
male; *methylation; mouse; mouse model; mouse mutant; *nonalcoholic
steatohepatitis; nonhuman; *obesity; reduced representation bisulfite sequencing;
signal transduction; Wnt signaling
Abstract
Background: About 24% of the world's population is affected by nonalcoholic fatty
liver disease, which may progress to nonalcoholic steatohepatitis (NASH),
cirrhosis, and hepatocellular carcinoma (HCC). Interestingly NASH-HCC has been
observed in both lean and obese individuals, however, the mechanisms by which HCC
develops in these two settings is not known. Furthermore, the role of epigenetic
changes in liver carcinogenesis in the context of lean and obese NASH-HCC is not
well understood. Method(s): We used mouse models of lean and obese NASH-HCC we have
previously generated using a choline deficient/high trans-fat/fructose/cholesterol
(CD-HFFC) diet and a choline supplemented/high trans-fat/fructose/cholesterol diet
(CS-HFFC), respectively to obtain tissues that represent different stages of NASH-
HCC progression. We used reduced representation bisulfite sequencing to evaluate
methylation differences by investigating differentially methylated regions in HCC
progression in lean versus obese mice. Result(s): We identified a larger number of
differentially methylated regions (DMRs) in NASH-HCC progression in obese mice
compared to lean mice. There was no overlap in the DMRs with the largest
methylation differences observed between the two models (lean and obese). In the
lean NASH-HCCs, methylation differences were seen in genes associated with cancer
progression and prognosis (including HCC), such as CHCHD2, FSCN1, and ZDHHC12, and
lipid metabolism, including PNPLA6 and LDLRAP1. In obese NASH-HCC, methylation
differences were seen in genes known to be associated with HCC, including RNF217,
GJA8, PTPRE, PSAPL1, and LRRC8D. Genes involved in Wnt-signaling pathways were
enriched in hypomethylated DMRs in obese NASH-HCC. Conclusion(s): Our results
suggest that differential methylation may play a role in hepatocarcinogenesis in
lean versus obese NASH-HCC. Obese NASH-HCC may be driven by hypomethylation of Wnt
signaling pathwayrelated genes, while progression of lean NASH-HCC may be driven by
other signaling pathways, including lipid metabolism.
3350&isbn=&volume=76&issue=Supplement+1&spage=S1361&pages=S1361&date=2022&title=Hep
atology&atitle=DIFFERENTIAL+METHYLATION+PATTERNS+IN+LEAN+AND+OBESE+NONALCOHOLIC+STE
ATOHEPATITIS-INDUCED+HEPATOCELLULAR+CARCINOMA+IN+THE+MOUSE&aulast=Hymel&pid=
%3Cauthor%3EHymel+E.%3BFisher+K.%3BFarazi+P.%3C%2Fauthor%3E%3CAN%3E639719417%3C
%2FAN%3E%3CDT%3EConference+Abstract%3C%2FDT%3E
<22>
Accession Number
639453329
Title
THE DIAGNOSTIC ROLE OF CYTOKERATIN 8/18 IMMUNOHISTOCHEMICAL MARKER FOR LEAN NON-
ALCOHOLIC FATTY LIVER DISEASE.
Source
United European Gastroenterology Journal. Conference: 30th United European
Gastroenterology Week, UEG Week 2022. Virtual. 10(Supplement 8) (pp 899-900), 2022.
Date of Publication: October 2022.
Author
Telli P.; Buyuk M.; Ozturk N.B.; Istemihan Z.; Nuriyev K.; Atasoy A.; Cavus B.;
Cifcibasi Ormeci A.; Akyuz U.; Demir K.; Besisik F.; Kaymakoglu S.; Gulluoglu M.;
Akyuz F.
Institution
(Telli) Istanbul University Istanbul Faculty of Medicine, Internal Medicine,
Istanbul, Turkey
(Buyuk, Gulluoglu) Istanbul University, Istanbul Faculty of Medicine, Clinical
Pathology, Istanbul, Turkey
(Ozturk) Mayo Clinic, Minnesota, United States
(Istemihan, Nuriyev, Cavus, Cifcibasi Ormeci, Demir, Besisik, Kaymakoglu)
Istanbul University Istanbul, Faculty of Medicine, Gastroenterology, Istanbul,
Turkey
(Atasoy) Istanbul Aydin University, Faculty of Medicine, Gastroenterology,
Istanbul, Turkey
(Akyuz) Istanbul Health Sciences University, Fatih Sultan Mehmet Training and
Research Hospital, Dept. of Gastroenterology, Istanbul, Turkey
(Akyuz) Istanbul University Istanbul, Faculty of Medicine,
Gastroenterohepatology, Istanbul, Turkey
Publisher
Subject Headings
adult
alanine aminotransferase blood level
*algorithm
body mass
clinical article
clinical research
conference abstract
controlled study
demography
*diagnostic value
differential diagnosis
fatty liver
female
gender
glucose blood level
hematocrit
histopathology
human
human tissue
*immunohistochemistry
inflammation
information center
liver biopsy
liver cell
liver injury
male
*protein function
scoring system
bilirubin glucuronide
cytokeratin 18
*cytokeratin 8
endogenous compound
hemoglobin
hemoglobin A1c
Drug Index Terms
bilirubin glucuronide; cytokeratin 18; *cytokeratin 8; endogenous compound;
hemoglobin; hemoglobin A1c
Other Index Terms
adult; alanine aminotransferase blood level; *algorithm; body mass; clinical
article; clinical research; conference abstract; controlled study; demography;
*diagnostic value; differential diagnosis; fatty liver; female; gender; glucose
blood level; hematocrit; histopathology; human; human tissue;
*immunohistochemistry; inflammation; information center; liver biopsy; liver cell;
liver injury; male; *nonalcoholic fatty liver; Nonalcoholic Fatty Liver Disease
Activity Score; nonalcoholic steatohepatitis; *protein function; scoring system;
Abstract
Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the leading
causes of chronic liver diseases. NAFLD spectrum begins from simple steatosis to
non-alcoholic steatohepatitis (NASH), progressive fibrosis, cirrhosis, and even
hepatocellular carcinoma. Although most NAFLD patients are overweight and obese,
30% are lean. We analyzed lean and non-lean NAFLD patients' liver biopsies for
cytokeratin 8/18 immunohistochemical staining differences. Aims & Methods: Thirty
biopsy-proven NAFLD patients (15 patients with BMI <= 25 kg/m2, 15 patients with
BMI > 25 kg/m2) were included in the study. Demographic, biochemical, and
histologic features of the patients were recorded. Biopsy specimens from our
archive were re-stained with cytokeratin 8/18 marker and were re-evaluated by a
single expert hepatopathologist according to Brunt's classification, the NASH
Clinical Research Network (NASH-CRN) scoring system, and fatty liver inhibition of
progression (FLIP) algorithm. Result(s): The presence of pathological granular
staining with cytokeratin 8/18 marker in hepatocytes positively correlated with
ballooning degeneration (r=0.461, p=0.027), the grade of lobular inflammation
according to the FLIP algorithm (r=0.461, p=0.027), the grade of lobular
inflammation according to the NAFLD activity score (r=0.545, p=0.007), presence of
portal inflammation (r=0.525, p=0.010), age (r=0.534, p=0.009), gender (r=0.464,
p=0.026), serum glucose value (r=0.537, p=0.008), direct bilirubin (r=0.523,
p=0.022) and HbA1c (r=0.758, p=0.029) levels, and negatively correlated with
hemoglobin (r=-0.473, p=0.030) and hematocrit (r=-0.437, p=0.047) levels. There was
no significant difference in the presence or staining pattern of cytokeratin 8/18
marker between the two groups. In the lean NAFLD group, liver damage was milder,
serum triglyceride levels were lower (p=0.003) and ALT values were higher (p=0.031)
compared to the non-lean group. Conclusion(s): Although the presence of cytokeratin
8/18 immune marker staining has no role in the differential diagnosis of lean and
non-lean NAFLD, the presence of granular staining may be an indicator of
progression.
sid=OVID:embase&id=pmid:&id=doi:10.1002%2Fueg2.12290&issn=2050-
6414&isbn=&volume=10&issue=Supplement+8&spage=899&pages=899-
900&date=2022&title=United+European+Gastroenterology+Journal&atitle=THE+DIAGNOSTIC+
ROLE+OF+CYTOKERATIN+8%2F18+IMMUNOHISTOCHEMICAL+MARKER+FOR+LEAN+NON-
ALCOHOLIC+FATTY+LIVER+DISEASE&aulast=Telli&pid=%3Cauthor%3ETelli+P.%3BBuyuk+M.
%3BOzturk+N.B.%3BIstemihan+Z.%3BNuriyev+K.%3BAtasoy+A.%3BCavus+B.
%3BCifcibasi+Ormeci+A.%3BAkyuz+U.%3BDemir+K.%3BBesisik+F.%3BKaymakoglu+S.
%3BGulluoglu+M.%3BAkyuz+F.%3C%2Fauthor%3E%3CAN%3E639453329%3C%2FAN%3E%3CDT
<23>
Accession Number
639444219
PMID
Title
Epidemiology and Prevalence of Lean Non-Alcoholic Fatty Liver Disease and
Associated Cirrhosis, HCC and Cardiovascular Outcomes in the United States: A
Population-Based Study and Review of Literature.
Source
Journal of gastroenterology and hepatology. (no pagination), 2022. Date of
Publication: 03 Nov 2022.
Author
Almomani A.; Kumar P.; Onwuzo S.; Boustany A.; Krishtopaytis E.; Hitawala A.;
Alshaikh D.; Albakri A.; Hussein L.; Hussein E.; Asaad I.
Author NameID
Almomani, Ashraf; ORCID: https://orcid.org/0000-0003-1648-0005
Boustany, Antoine; ORCID: https://orcid.org/0000-0002-4661-1443
Hussein, Leen; ORCID: https://orcid.org/0000-0002-3428-9282
Institution
(Almomani, Kumar, Onwuzo, Boustany, Krishtopaytis, Asaad) Cleveland Clinic
Foundation, Cleveland, United States
(Hitawala) National Institute of Health, MD, United States
(Alshaikh) Mutah University, Jordan
(Albakri) Jordanian Royal Medical Services, Amman, Jordan
(Hussein, Hussein) Al Andalus University for Medical Sciences, Tartus, Syrian
Arab Republic
Publisher
NLM (Medline)
Subject Headings
adult
alcohol liver disease
alpha 1 antitrypsin deficiency
article
autoimmune hepatitis
biliary cirrhosis
body mass
cancer patient
cohort analysis
complication
confounding variable
coronary artery disease
cystic fibrosis
esophagus varices
female
hemochromatosis
human
*literature
*liver cirrhosis
obesity
outcome assessment
*prevalence
race
risk factor
smoking
systematic review
*United States
virus hepatitis
Wilson disease
alpha 1 antitrypsin
endogenous compound
Drug Index Terms
alpha 1 antitrypsin [m]; endogenous compound [m]
Other Index Terms
acute coronary syndrome [m]; adult [m]; alcohol liver disease [m]; alpha 1
antitrypsin deficiency [m]; article [m]; autoimmune hepatitis [m]; biliary
cirrhosis [m]; body mass [m]; cancer patient [m]; cohort analysis [m]; complication
[m]; confounding variable [m]; coronary artery disease [m]; cystic fibrosis [m];
esophagus varices [m]; female [m]; hemochromatosis [m]; human [m]; *literature [m];
liver cell carcinoma [m]; *liver cirrhosis [m]; metabolic syndrome X [m];
*nonalcoholic fatty liver [m]; obesity [m]; outcome assessment [m]; *prevalence
[m]; race [m]; risk factor [m]; smoking [m]; systematic review [m]; *United States
[m]; virus hepatitis [m]; Wilson disease [m]
Abstract
BACKGROUNDS: NAFLD is linked to obesity and metabolic syndrome conditions.
However, a subset of NAFLD patients express a normal or low body mass index (Lean
NAFLD, L-NAFLD). Our aim is to compare the prevalence of L-NAFLD to the obesity-
associated NAFLD in the United States by assessing prevalence, potential risk
factors, liver-related complications and coronary artery disease outcomes.
METHODOLOGY: A multi-center database (Explorys Inc.) of >70 million patients across
the US was screened. A cohort of patients with "Non-Alcoholic Fatty Liver" between
1999-2021 was identified. two sub-cohorts of NAFLD patients were identified; those
with a Body Mass Index (BMI) <25 kg/m2 (Lean NAFLD) and those with a BMI >30 kg/m2
(Obesity-associated NAFLD). We excluded patients with age<18, and those who have
viral hepatitis, hemochromatosis, Wilson's disease, biliary cirrhosis, alcoholic
liver disease, cystic fibrosis, alpha-1-antitrypsin deficiency, and autoimmune
hepatitis. Multivariate analysis was performed to adjust for confounders.
RESULT(S): 68,892,260 individuals were screened. NAFLD prevalence was 4 per 100,000
and L-NAFLD prevalence was 0.6 per 100,000. Comparing to those without, patients
with L-NAFLD tended to be older (OR 2.16), females (OR 1.28), smokers (OR 4.67) and
of Asian race (OR 2.12). L-NAFLD patients were more likely to have Acute Coronary
Syndromes (ACS) (OR 30.00) and metabolic syndrome (OR 2.31) despite the normal/low
BMI. Esophageal varices (EV) and hepatocellular carcinoma risks were high in both
cirrhosis patients. CONCLUSION(S): This is the largest study to assess L-NAFLD
prevalence in the US. L-NAFLD are at a significantly higher risk for ACS, EV and
HCC.Copyright This article is protected by copyright. All rights reserved.
1746&isbn=&volume=38&issue=2&spage=269&pages=&date=2022&title=Journal+of+gastroente
rology+and+hepatology&atitle=Epidemiology+and+Prevalence+of+Lean+Non-
Alcoholic+Fatty+Liver+Disease+and+Associated+Cirrhosis
%2C+HCC+and+Cardiovascular+Outcomes+in+the+United+States%3A+A+Population-
Based+Study+and+Review+of+Literature&aulast=Almomani&pid=%3Cauthor%3EAlmomani+A.
%3BKumar+P.%3BOnwuzo+S.%3BBoustany+A.%3BKrishtopaytis+E.%3BHitawala+A.
%3BAlshaikh+D.%3BAlbakri+A.%3BHussein+L.%3BHussein+E.%3BAsaad+I.%3C%2Fauthor%3E
%3CAN%3E639444219%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<24>
Accession Number
2019872340
PMID
Title
Differential progression of unhealthy diet-induced hepatocellular carcinoma in
obese and non-obese mice.
Source
PLoS ONE. 17(8 August) (no pagination), 2022. Article Number: e0272623. Date of
Publication: August 2022.
Author
Hymel E.; Vlock E.; Fisher K.W.; Farazi P.A.
Institution
(Hymel, Vlock, Farazi) Department of Epidemiology, College of Public Health,
University of Nebraska Medical Center, Omaha, NE, United States
(Vlock, Farazi) Nebraska Center for the Prevention of Obesity Diseases through
Dietary Molecules, College of Education and Human Sciences, University of Nebraska
Lincoln, Lincoln, NE, United States
(Fisher) Department of Pathology and Microbiology, College of Medicine,
Publisher
Public Library of Science
Subject Headings
animal cell
animal experiment
animal model
animal tissue
article
body weight gain
cancer free survival
*cancer growth
cholesterol blood level
cholesterol diet
choline deficiency
controlled study
diet composition
fatty acid blood level
fatty acid metabolism
female
glucose intolerance
histology
histopathology
insulin resistance
lipid fingerprinting
male
metabolomics
molecular pathology
mouse
mouse model
nonhuman
penetrance
tumor volume
*unhealthy diet
cholesterol/ec [Endogenous Compound]
choline
colony stimulating factor 1/ec [Endogenous Compound]
complement component C5/ec [Endogenous Compound]
complement component C5a/ec [Endogenous Compound]
fatty acid/ec [Endogenous Compound]
fructose
glucose/ip [Intraperitoneal Drug Administration]
insulin/ip [Intraperitoneal Drug Administration]
polyunsaturated fatty acid/ec [Endogenous Compound]
stromal cell derived factor 1/ec [Endogenous Compound]
tissue inhibitor of metalloproteinase 1/ec [Endogenous Compound]
Drug Index Terms
alanine aminotransferase / endogenous compound; aspartate aminotransferase /
endogenous compound; cholesterol / endogenous compound; choline; colony stimulating
factor 1 / endogenous compound; complement component C5 / endogenous compound;
complement component C5a / endogenous compound; fatty acid / endogenous compound;
fructose; glucose / intraperitoneal drug administration; insulin / intraperitoneal
drug administration; polyunsaturated fatty acid / endogenous compound; stromal cell
derived factor 1 / endogenous compound; tissue inhibitor of metalloproteinase 1 /
endogenous compound; triacylglycerol / endogenous compound
Other Index Terms
animal cell; animal experiment; animal model; animal tissue; Article; body weight
gain; cancer free survival; *cancer growth; cholesterol blood level; cholesterol
diet; choline deficiency; controlled study; diet composition; *diet-induced
obesity; fatty acid blood level; fatty acid metabolism; female; glucose
intolerance; high fat/high fructose diet; histology; histopathology; insulin
resistance; lipid fingerprinting; liver carcinogenesis; *liver cell carcinoma /
*etiology; male; metabolomics; molecular pathology; mouse; mouse model;
nonalcoholic steatohepatitis; nonhuman; penetrance; triacylglycerol blood level;
tumor volume; *unhealthy diet
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) ranks first among liver
diseases in Western countries. NAFLD is typically associated with obesity and
diabetes, however it also develops in lean individuals without metabolic syndrome.
The prevalence of lean NAFLD is 7 percent in the U.S. and 25-30 percent in some
Asian countries. NAFLD starts with excess liver fat accumulation (NAFL), progresses
to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma
(HCC). The pathogenesis of lean NASH-HCC and how it differs from obese NASH-HCC is
not well understood. Methods In this work, we generated a mouse model of lean and
obese NASH-HCC using a choline deficient/high trans-fat/fructose/cholesterol diet
and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively,
to compare progression to NASH-HCC in lean versus obese mice. Comparisons were made
at the organismal, histological, and molecular level by investigating fatty acid
metabolism in the plasma of these mice. Results Obese mice showed more pronounced
glucose intolerance and insulin resistance, higher levels of plasma cholesterol and
triglycerides, and higher penetrance of NASH compared to lean mice. Despite the
abnormal metabolic profile of obese mice, male obese and lean mice developed HCC
with similar penetrance (53.3% and 53.8%, respectively), albeit lean mice showed
faster tumor progression as evidenced by the larger tumor size and lower HCC-free
survival. None of the female lean mice developed HCC, while 50% of female obese
mice developed HCC. Both groups of mice showed a reduction in plasma
polyunsaturated fatty acids (PUFAs), however, the levels were higher towards the
endpoint in obese mice compared to lean mice. Conclusions Unhealthy diet
composition appears to drive progression to NASH-HCC rather than the organismal
effects of obesity. PUFA levels may increase due to systemic inflammation in obese
mice and act as suppressors of tumor progression, thus delaying HCC progression in
obese mice compared to lean mice. These models could be used to further dissect the
molecular pathogenesis of lean and obese NASH-HCC and address the mechanisms
whereby PUFAs may be implicated in hepatocarcinogenesis.Copyright: © 2022 Hymel et
al. This is an open access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original author and source are credited.
T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed23&AN=2019872340
sid=OVID:embase&id=pmid:35994501&id=doi:10.1371%2Fjournal.pone.0272623&issn=1932-
6203&isbn=&volume=17&issue=8+August&spage=e0272623&pages=&date=2022&title=PLoS+ONE&
atitle=Differential+progression+of+unhealthy+diet-
induced+hepatocellular+carcinoma+in+obese+and+non-obese+mice&aulast=Hymel&pid=
%3Cauthor%3EHymel+E.%3BVlock+E.%3BFisher+K.W.%3BFarazi+P.A.%3C%2Fauthor%3E%3CAN
<25>
Accession Number
2019190554
Title
MiR-22 Deficiency Fosters Hepatocellular Carcinoma Development in Fatty Liver.
Source
Cells. 11(18) (no pagination), 2022. Article Number: 2860. Date of Publication:
September 2022.
Author
Gjorgjieva M.; Ay A.-S.; Correia de Sousa M.; Delangre E.; Dolicka D.; Sobolewski
C.; Maeder C.; Fournier M.; Sempoux C.; Foti M.
Author NameID
Gjorgjieva, Monika; ORCID: https://orcid.org/0000-0001-8553-7525
Sobolewski, Cyril; ORCID: https://orcid.org/0000-0002-9404-6290
Foti, Michelangelo; ORCID: https://orcid.org/0000-0001-7199-4135
Institution
(Gjorgjieva, Ay, Correia de Sousa, Delangre, Dolicka, Sobolewski, Maeder,
Fournier, Foti) Department of Cell Physiology and Metabolism, Faculty of Medicine,
University of Geneva, Geneva CH-1211, Switzerland
(Sempoux) Service of Clinical Pathology, Institute of Pathology, Lausanne
University Hospital, University of Lausanne, Lausanne CH-1011, Switzerland
(Foti) Translational Research Centre in Onco-Haematology, Faculty of Medicine,
University of Geneva, Geneva CH-1211, Switzerland
Publisher
MDPI
Subject Headings
AML12 cell line
animal cell
animal experiment
animal housing
animal model
animal tissue
article
bicinchoninic acid assay
bioinformatics
blood analysis
cancer growth
cancer patient
carcinogenesis
cell culture
cell migration assay
cell proliferation
cholesterol metabolism
computer assisted tomography
computer model
diet-induced obesity
diethylnitrosamine-induced hepatocarcinogenesis
down regulation
fatty acid oxidation
*fatty liver
gene expression
gene mutation
gene ontology
gene overexpression
gene silencing
genetic transfection
genotyping
glucose blood level
glycolysis
Hep-G2 cell line
histopathology
Huh-7 cell line
human
human cell
in vitro study
in vivo study
incidence
insulin tolerance test
lipid diet
liver cell
liver tissue
luciferase assay
metabolism
micro-computed tomography
mitochondrial respiration
mouse
mouse model
nonhuman
oncogene
oxidative stress
pleiotropy
proteomics
reverse transcription polymerase chain reaction
software
steatohepatitis
survival analysis
transcriptomics
tumor suppressor gene
upregulation
wild type mouse
adenosine triphosphate/ec [Endogenous Compound]
diethylnitrosamine
etomoxir/ec [Endogenous Compound]
glucose/ip [Intraperitoneal Drug Administration]
long chain fatty acid/ec [Endogenous Compound]
*microRNA 22/ec [Endogenous Compound]
proteome/ec [Endogenous Compound]
small interfering RNA/ec [Endogenous Compound]
thrombospondin 1/ec [Endogenous Compound]
analyzer
immunoassay analyzer
polymerase chain reaction system
reverse transcriptase PCR assay kit
RNA interference assay kit
Device Index Terms
analyzer; immunoassay analyzer; polymerase chain reaction system; reverse
transcriptase PCR assay kit; RNA interference assay kit
Drug Index Terms
adenosine triphosphate / endogenous compound; diethylnitrosamine; etomoxir /
endogenous compound; glucose / intraperitoneal drug administration; long chain
fatty acid / endogenous compound; *microRNA 22 / *endogenous compound; proteome /
endogenous compound; small interfering RNA / endogenous compound; thrombospondin
1 / endogenous compound
Other Index Terms
AML12 cell line; animal cell; animal experiment; animal housing; animal model;
animal tissue; Article; bicinchoninic acid assay; bioinformatics; blood analysis;
cancer growth; cancer patient; carcinogenesis; cell culture; cell migration assay;
cell proliferation; cholesterol metabolism; computer assisted tomography; computer
model; diet-induced obesity; diethylnitrosamine-induced hepatocarcinogenesis; down
regulation; fatty acid oxidation; *fatty liver; gene expression; gene mutation;
gene ontology; gene overexpression; gene silencing; genetic transfection;
genotyping; glucose blood level; glycolysis; Hep-G2 cell line; histopathology; Huh-
7 cell line; human; human cell; in vitro study; in vivo study; incidence; insulin
tolerance test; lipid diet; liver cell; *liver cell carcinoma; liver tissue;
luciferase assay; metabolism; micro-computed tomography; mitochondrial respiration;
mouse; mouse model; nonalcoholic fatty liver; nonhuman; oncogene; oxidative stress;
pleiotropy; proteomics; reverse transcription polymerase chain reaction; software;
steatohepatitis; survival analysis; transcriptomics; tumor suppressor gene;
upregulation; wild type mouse
Abstract
MiR-22 is mostly considered as a hepatic tumor-suppressor microRNA based on in
vitro analyses. Yet, whether miR-22 exerts a tumor-suppressive function in the
liver has not been investigated in vivo. Herein, in silico analyses of miR-22
expression were performed in hepatocellular carcinomas from human patient cohorts
and different mouse models. Diethylnitrosamine-induced hepatocellular carcinomas
were then investigated in lean and diet-induced obese miR-22-deficient mice. The
proteome of liver tissues from miR-22-deficient mice prior to hepatocellular
carcinoma development was further analyzed to uncover miR-22 regulated factors that
impact hepatocarcinogenesis with miR-22 deficiency. MiR-22 downregulation was
consistently observed in hepatocellular carcinomas from all human cohorts and mouse
models investigated. The time of appearance of the first tumors was decreased and
the number of tumoral foci induced by diethylnitrosamine was significantly
increased by miR-22-deficiency in vivo, two features which were further drastically
exacerbated with diet-induced obesity. At the molecular level, we provide evidence
that the loss of miR-22 significantly affects the energetic metabolism and
mitochondrial functions of hepatocytes, and the expression of tumor-promoting
factors such as thrombospondin-1. Our study demonstrates that miR-22 acts as a
hepatic tumor suppressor in vivo by restraining pro-carcinogenic metabolic
deregulations through pleiotropic mechanisms and the overexpression of relevant
oncogenes.Copyright © 2022 by the authors.
sid=OVID:embase&id=pmid:&id=doi:10.3390%2Fcells11182860&issn=2073-
4409&isbn=&volume=11&issue=18&spage=2860&pages=&date=2022&title=Cells&atitle=MiR-
22+Deficiency+Fosters+Hepatocellular+Carcinoma+Development+in+Fatty+Liver&aulast=Gj
orgjieva&pid=%3Cauthor%3EGjorgjieva+M.%3BAy+A.-S.%3BCorreia+de+Sousa+M.
%3BDelangre+E.%3BDolicka+D.%3BSobolewski+C.%3BMaeder+C.%3BFournier+M.%3BSempoux+C.
%3BFoti+M.%3C%2Fauthor%3E%3CAN%3E2019190554%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<26>
Accession Number
2017928189
PMID
Title
Metabolic (dysfunction)-associated fatty liver disease in individuals of normal
weight.
Source
Nature Reviews Gastroenterology and Hepatology. 19(10) (pp 638-651), 2022. Date
Author
Eslam M.; El-Serag H.B.; Francque S.; Sarin S.K.; Wei L.; Bugianesi E.; George J.
Author NameID
Eslam, Mohammed; ORCID: https://orcid.org/0000-0002-4315-4144
George, Jacob; ORCID: https://orcid.org/0000-0002-8421-5476
El-Serag, Hashem B.; ORCID: https://orcid.org/0000-0001-5964-7579
Francque, Sven; ORCID: https://orcid.org/0000-0002-7527-4714
Sarin, Shiv K.; ORCID: https://orcid.org/0000-0002-0544-5610
Institution
(Eslam, George) Storr Liver Centre, Westmead Institute for Medical Research,
Westmead Hospital and University of Sydney, Sydney, NSW, Australia
(El-Serag) Department of Medicine, Baylor College of Medicine, Houston, TX,
United States
(Francque) Department of Gastroenterology and Hepatology, Antwerp University
Hospital, Antwerp, Belgium
(Francque) Laboratory of Experimental Medicine and Paediatrics (LEMP), Faculty of
Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
(Sarin) Department of Hepatology, Institute of Liver and Biliary Sciences, New
Delhi, India
(Wei) Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital,
Tsinghua University, Beijing, China
(Bugianesi) Department of Medical Sciences, Division of Gastroenterology and
Hepatology, A.O. Citta della Salute e della Scienza di Torino, University of Turin,
Turin, Italy
Publisher
Nature Research
Subject Headings
adaptation
*body weight
body weight gain
genetic correlation
histology
human
*metabolic fatty liver/di [Diagnosis]
*metabolic fatty liver/ep [Epidemiology]
*metabolic fatty liver/et [Etiology]
metabolic parameters
metabolism
nonhuman
pathogenesis
pathophysiology
patient care
phenotype
prognosis
review
Other Index Terms
adaptation; *body weight; body weight gain; genetic correlation; histology;
human; *metabolic fatty liver / *diagnosis / *epidemiology / *etiology; metabolic
parameters; metabolism; nonhuman; pathogenesis; pathophysiology; patient care;
phenotype; prognosis; Review
Abstract
Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects up to a
third of the global population; its burden has grown in parallel with rising rates
of type 2 diabetes mellitus and obesity. MAFLD increases the risk of end-stage
liver disease, hepatocellular carcinoma, death and liver transplantation and has
extrahepatic consequences, including cardiometabolic disease and cancers. Although
typically associated with obesity, there is accumulating evidence that not all
people with overweight or obesity develop fatty liver disease. On the other hand, a
considerable proportion of patients with MAFLD are of normal weight, indicating the
importance of metabolic health in the pathogenesis of the disease regardless of
body mass index. The clinical profile, natural history and pathophysiology of
patients with so-called lean MAFLD are not well characterized. In this Review, we
provide epidemiological data on this group of patients and consider overall
metabolic health and metabolic adaptation as a framework to best explain the
pathogenesis of MAFLD and its heterogeneity in individuals of normal weight and in
those who are above normal weight. This framework provides a conceptual schema for
interrogating the MAFLD phenotype in individuals of normal weight that can
translate to novel approaches for diagnosis and patient care.Copyright © 2022,
Springer Nature Limited.
651&date=2022&title=Nature+Reviews+Gastroenterology+and+Hepatology&atitle=Metabolic
+%28dysfunction%29-
associated+fatty+liver+disease+in+individuals+of+normal+weight&aulast=Eslam&pid=
%3Cauthor%3EEslam+M.%3BEl-Serag+H.B.%3BFrancque+S.%3BSarin+S.K.%3BWei+L.
%3BBugianesi+E.%3BGeorge+J.%3C%2Fauthor%3E%3CAN%3E2017928189%3C%2FAN%3E%3CDT
<27>
Accession Number
2017427325
PMID
Title
A diet-induced murine model for non-alcoholic fatty liver disease with obesity
and insulin resistance that rapidly develops steatohepatitis and fibrosis.
Source
Laboratory Investigation. 102(10) (pp 1150-1157), 2022. Date of Publication:
October 2022.
Author
Sakuma T.; Nakamura M.; Chiba T.; Iwanaga T.; Kan M.; Kojima R.; Ao J.; Ma Y.;
Unozawa H.; Fujita N.; Kanayama K.; Kanzaki H.; Koroki K.; Kobayashi K.; Nakagawa
R.; Kanogawa N.; Kiyono S.; Kondo T.; Saito T.; Ogasawara S.; Nakamoto S.; Muroyama
R.; Kato J.; Kishimoto T.; Kato N.
Author NameID
Nakamura, Masato; ORCID: https://orcid.org/0000-0003-4080-2967
Institution
(Sakuma, Nakamura, Chiba, Iwanaga, Kan, Kojima, Ao, Ma, Unozawa, Fujita,
Kanayama, Kanzaki, Koroki, Kobayashi, Nakagawa, Kanogawa, Kiyono, Kondo, Saito,
Ogasawara, Nakamoto, Kato, Kato) Department of Gastroenterology, Chiba University,
Graduate School of Medicine, Chiba 260-8677, Japan
(Kobayashi, Ogasawara) Translational Research and Development Center, Chiba
University Hospital, Chiba 260-8677, Japan
(Muroyama) Department of Molecular Virology, Chiba University, Graduate School of
(Kishimoto) Department of Molecular Pathology, Chiba University, Graduate School
of Medicine, Chiba 260-8677, Japan
Publisher
Springer Nature
Subject Headings
animal experiment
animal model
animal tissue
article
body weight gain
C57BL 6 mouse
caloric intake
cholesterol diet
cholesterol liver level
chow diet
controlled study
dyslipidemia
food intake
glucose blood level
histopathology
insulin level
*insulin resistance
KK-Ay mouse
lipid metabolism
lipid storage
*liver fibrosis
liver weight
mesenteric fat
mouse
mouse strain
*murine model
nonhuman
*obesity
quantitative analysis
*steatohepatitis
supplementation
triacylglycerol level
*cholic acid
glucose/ec [Endogenous Compound]
ELISA kit
nucleic acid isolation kit
reverse transcriptase PCR assay kit
Device Index Terms
ELISA kit; nucleic acid isolation kit; reverse transcriptase PCR assay kit
Drug Index Terms
cholesterol / endogenous compound; *cholic acid; glucose / endogenous compound;
insulin / endogenous compound; triacylglycerol / endogenous compound
Other Index Terms
animal experiment; animal model; animal tissue; Article; body weight gain; C57BL
6 mouse; caloric intake; cholesterol diet; cholesterol liver level; chow diet;
controlled study; dyslipidemia; food intake; glucose blood level; high fat/high
fructose diet; histopathology; insulin level; *insulin resistance; KK-Ay mouse;
lipid metabolism; lipid storage; *liver fibrosis; liver weight; mesenteric fat;
mouse; mouse strain; *murine model; *nonalcoholic fatty liver; nonhuman; *obesity;
quantitative analysis; *steatohepatitis; supplementation; triacylglycerol level
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic
liver disease worldwide. Patients with NAFLD often suffer steatohepatitis, which
can progress to cirrhosis and hepatocellular carcinoma. The presence of visceral
obesity or type 2 diabetes mellitus (T2DM) is a major risk factor and potential
therapeutic target for NAFLD. The establishment of animal models with these
metabolic comorbidities and with the rapid progression of the disease is needed for
developing treatments for NAFLD but remains to be archived. In the present study,
KK-Ay mice, widely used as T2DM models, or C57BL6 mice were fed a high-fat, high-
fructose, and high-cholesterol diet supplemented with cholic acid (NAFLD diet). The
KK-Ay mice fed a NAFLD diet exhibited remarkable obesity and insulin resistance. A
prominent accumulation of triglycerides and cholesterol in the liver was observed
at 4 weeks. These mice developed steatohepatitis at 4 weeks and fibrosis at 12
weeks. In contrast, C57BL6 mice fed a NAFLD diet remained lean, although they still
developed steatohepatitis and fibrosis. In summary, we established a diet-induced
murine NAFLD model with the rapid development of steatohepatitis and fibrosis,
bearing obesity and insulin resistance. This model could be useful as preclinical
models for drug development of NAFLD.Copyright © 2022, The Author(s), under
exclusive licence to United States and Canadian Academy of Pathology.
1157&date=2022&title=Laboratory+Investigation&atitle=A+diet-
induced+murine+model+for+non-
alcoholic+fatty+liver+disease+with+obesity+and+insulin+resistance+that+rapidly+deve
lops+steatohepatitis+and+fibrosis&aulast=Sakuma&pid=%3Cauthor%3ESakuma+T.
%3BNakamura+M.%3BChiba+T.%3BIwanaga+T.%3BKan+M.%3BKojima+R.%3BAo+J.%3BMa+Y.
%3BUnozawa+H.%3BFujita+N.%3BKanayama+K.%3BKanzaki+H.%3BKoroki+K.%3BKobayashi+K.
%3BNakagawa+R.%3BKanogawa+N.%3BKiyono+S.%3BKondo+T.%3BSaito+T.%3BOgasawara+S.
%3BNakamoto+S.%3BMuroyama+R.%3BKato+J.%3BKishimoto+T.%3BKato+N.%3C%2Fauthor%3E%3CAN
<28>
Accession Number
2019268697
PMID
Title
AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty
Liver Disease in Lean Individuals: Expert Review.
Source
Gastroenterology. 163(3) (pp 764-774.e1), 2022. Date of Publication: September
2022.
Author
Long M.T.; Noureddin M.; Lim J.K.
Author NameID
Long, Michelle T.; ORCID: https://orcid.org/0000-0001-6131-3981
Institution
(Long) Section of Gastroenterology, Boston Medical Center, Boston University
School of Medicine, Boston, Massachusetts
(Noureddin) Fatty Liver Program, Karsh Division of Gastroenterology and
Hepatology, Cedars Sinai Medical Center, Los Angeles, California
(Lim) Section of Digestive Diseases and Yale Liver Center, Yale University School
of Medicine, New Haven, Connecticut
Publisher
W.B. Saunders
Subject Headings
alcohol consumption
all cause mortality
article
body mass
clinical evaluation
*clinical practice
comorbidity
diet therapy
dyslipidemia
enzyme deficiency
ethnic or racial aspects
evidence based practice
exercise
familial hypobetalipoproteinemia
follow up
genetic variability
HIV associated lipodystrophy
human
hypertension
lipodystrophy
liver fibrosis
liver injury
magnetic resonance elastography
medical society
*nonalcoholic fatty liver/di [Diagnosis]
peer review
practice guideline
Other Index Terms
alcohol consumption; all cause mortality; Article; body mass; clinical
evaluation; *clinical practice; comorbidity; diet therapy; dyslipidemia; enzyme
deficiency; ethnic or racial aspects; evidence based practice; exercise; familial
hypobetalipoproteinemia; follow up; genetic variability; HIV associated
lipodystrophy; human; hypertension; lipodystrophy; liver fibrosis; liver injury;
magnetic resonance elastography; medical society; non insulin dependent diabetes
mellitus; *nonalcoholic fatty liver / *diagnosis; peer review; practice guideline
Abstract
Description: Nonalcoholic fatty liver disease (NAFLD) is well recognized as a
leading etiology for chronic liver disease, affecting >25% of the US and global
populations. Up to 1 in 4 individuals with NAFLD have nonalcoholic steatohepatitis,
which is associated with significant morbidity and mortality due to complications
of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although
NAFLD is observed predominantly in persons with obesity and/or type 2 diabetes
mellitus, an estimated 7%-20% of individuals with NAFLD have lean body habitus.
Limited guidance is available to clinicians on appropriate clinical evaluation in
lean individuals with NAFLD, such as for inherited/genetic disorders,
lipodystrophy, drug-induced NAFLD, and inflammatory disorders. Emerging data now
provide more robust evidence to define the epidemiology, natural history,
prognosis, and mortality of lean individuals with NAFLD. Multiple studies have
found that NAFLD among lean individuals is associated with increased
cardiovascular, liver, and all-cause mortality relative to those without NAFLD.
This American Gastroenterological Association Clinical Practice Update provides
Best Practice Advice to assist clinicians in evidence-based approaches to the
diagnosis, staging, and management of NAFLD in lean individuals. Method(s): This
expert review was commissioned and approved by the American Gastroenterological
Association (AGA) Institute Clinical Practice Updates Committee and the AGA
Governing Board to provide timely guidance on a topic of high clinical importance
to the AGA membership and underwent internal peer review by the Clinical Practice
Updates Committee and external peer review through standard procedures of
Gastroenterology. Best Practice Advice Statements Best Practice Advice 1: Lean
NAFLD should be diagnosed in individuals with NAFLD and body mass index <25 kg/m2
(non-Asian race) or body mass index <23 kg/m2 (Asian race). Best Practice Advice 2:
Lean individuals with NAFLD should be evaluated routinely for comorbid conditions,
such as type 2 diabetes mellitus, dyslipidemia, and hypertension. Best Practice
Advice 3: Lean individuals with NAFLD should be risk stratified for hepatic
fibrosis to identify those with advanced fibrosis or cirrhosis. Best Practice
Advice 4: Lean individuals in the general population should not undergo routine
screening for NAFLD; however, screening should be considered for individuals older
than 40 years with type 2 diabetes mellitus. Best Practice Advice 5: NAFLD should
be considered in lean individuals with metabolic diseases (such as type 2 diabetes
mellitus, dyslipidemia, and hypertension), elevated liver biochemical tests, or
incidentally noted hepatic steatosis. Best Practice Advice 6: Clinicians should
query patients routinely regarding alcohol consumption patterns in all patients
with lean NAFLD. Best Practice Advice 7: In patients with lean NAFLD, other causes
of liver disease should be ruled out, including other causes of fatty liver, such
as HIV, lipodystrophy, lysosomal acid lipase deficiency, familial
hypobetalipoproteinemia, and medication-induced hepatic steatosis (methotrexate,
amiodarone, tamoxifen, and steroids). Best Practice Advice 8: Current evidence is
inadequate to support routine testing for genetic variants in patients with lean
NAFLD. Best Practice Advice 9: Liver biopsy, as the reference standard, should be
considered if there is uncertainty regarding contributing causes of liver injury
and/or the stage of liver fibrosis. Best Practice Advice 10: Serum indices (NAFLD
fibrosis score and Fibrosis-4 score) and imaging techniques (transient elastography
and magnetic resonance elastography) may be used as alternatives to liver biopsy
for fibrosis staging and patient follow-up. These tests can be performed at the
time of diagnosis and repeated at intervals of 6 months to 2 years, depending on
fibrosis stage and the patient's response to intervention. Best Practice Advice 11:
If noninvasive tests (eg, Fibrosis-4 and NAFLD fibrosis score) are indeterminate, a
second noninvasive test (eg, transient elastography or magnetic resonance
elastography) should be performed to confirm the stage and prognosis of NAFLD. Best
Practice Advice 12: In lean patients with NAFLD, lifestyle intervention, including
exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks,
to target a modest weight loss of 3%-5% is suggested. Best Practice Advice 13:
Administration of vitamin E may be considered in lean persons with biopsy-confirmed
nonalcoholic steatohepatitis, but without type 2 diabetes mellitus or cirrhosis.
Oral pioglitazone 30 mg daily may be considered in lean persons with biopsy-
confirmed nonalcoholic steatohepatitis without cirrhosis. Best Practice Advice 14:
The therapeutic role of glucagon-like peptide-1 agonists and sodium-glucose
cotransporter-2 inhibitors in the management of lean NAFLD is not fully defined and
requires further investigation. Best Practice Advice 15: Hepatocellular carcinoma
surveillance with abdominal ultrasound with or without serum alpha-fetoprotein
twice per year is suggested in patients with lean NAFLD and clinical markers
compatible with liver cirrhosis.Copyright © 2022 AGA Institute
sid=OVID:embase&id=pmid:35842345&id=doi:10.1053%2Fj.gastro.2022.06.023&issn=0016-
774.e1&date=2022&title=Gastroenterology&atitle=AGA+Clinical+Practice+Update
%3A+Diagnosis+and+Management+of+Nonalcoholic+Fatty+Liver+Disease+in+Lean+Individual
s%3A+Expert+Review&aulast=Long&pid=%3Cauthor%3ELong+M.T.%3BNoureddin+M.%3BLim+J.K.
%3C%2Fauthor%3E%3CAN%3E2019268697%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<29>
Accession Number
2017830376
Title
Recent Epidemiology and Risk Factors of Nonalcoholic Fatty Liver Disease.
Source
Journal of Obesity and Metabolic Syndrome. 31(1) (pp 17-27), 2022. Date of
Publication: March 2022.
Author
Huh Y.; Cho Y.J.; Nam G.E.
Author NameID
Huh, Youn; ORCID: https://orcid.org/0000-0002-0960-5976
Nam, Ga Eun; ORCID: https://orcid.org/0000-0002-6739-9904
Institution
(Huh) Department of Family Medicine, Uijeongbu Eulji Medical Center, Eulji
University, School of Medicine, Uijeongbu, South Korea
(Cho) Department of Family Medicine, Daegu Catholic University, School of
Medicine, Daegu, South Korea
(Nam) Department of Family Medicine, Korea University, Guro Hospital, Korea
University, College of Medicine, Seoul, South Korea
Publisher
Korean Society for the Study of Obesity
Subject Headings
age
diet
disease burden
dyslipidemia
ethnic difference
genetic predisposition
human
incidence
insulin resistance
intestine flora
mortality
*nonalcoholic fatty liver/et [Etiology]
nonhuman
obesity
oxidative stress
physical activity
prevalence
race difference
review
*risk factor
sarcopenia
sex difference
sleep
Other Index Terms
age; diet; disease burden; disease exacerbation; dyslipidemia; ethnic difference;
genetic predisposition; human; incidence; insulin resistance; intestine flora;
metabolic syndrome X; mortality; non insulin dependent diabetes mellitus;
*nonalcoholic fatty liver / *epidemiology / *etiology; nonhuman; obesity; oxidative
stress; physical activity; prevalence; race difference; Review; *risk factor;
sarcopenia; sex difference; sleep
Abstract
Because of the global obesity epidemic, the incidence and prevalence of
nonalcoholic fatty liver disease (NAFLD) have increased worldwide, including among
Koreans. Recently, the incidence rate of NAFLD in Korea was reported to be 45.1 per
1,000 person-years, and the prevalence as approximately 30% depending on the
diagnostic methods used. The incidence of advanced fibrosis and hepatocellular
carcinoma, as well as all-cause and liver-related mortality in NAFLD patients has
increased substantially, imposing considerable public health costs in Korea.
Genetic, demographic, environmental, and clinical factors are involved in the
pathogenesis of NAFLD. Some genetic variants, such as patatin-like phospholipase
domain-containing 3 (PNPLA-3) and sorting and assembly machinery component 50
(SAMM-50), play a major role in the occurrence of NAFLD. The risk of NAFLD and
fibrosis increases with advancing age and in men. Nutritional factors, inadequate
exercise, and sleep duration are also associated with increased risk of NAFLD.
Obesity is a major risk factor for NAFLD; however, NAFLD in lean individuals has
been noted in recent studies. Insulin resistance, type 2 diabetes, and metabolic
syndrome and its components are closely associated with NAFLD development and liver
fibrosis with various underlying mechanisms. Sarcopenia likely shares a common
pathophysiology with NAFLD. The rapidly increasing incidence and prevalence of
NAFLD and its complications, as well as the associated healthcare burden, warrant
early assessment of NAFLD and its risk factors to prevent NAFLD-related
complications in high risk groups.Copyright © 2022 Korean Society for the Study of
Obesity
sid=OVID:embase&id=pmid:&id=doi:10.7570%2FJOMES22021&issn=2508-
27&date=2022&title=Journal+of+Obesity+and+Metabolic+Syndrome&atitle=Recent+Epidemio
logy+and+Risk+Factors+of+Nonalcoholic+Fatty+Liver+Disease&aulast=Huh&pid=%3Cauthor
%3EHuh+Y.%3BCho+Y.J.%3BNam+G.E.%3C%2Fauthor%3E%3CAN%3E2017830376%3C%2FAN%3E%3CDT
<30>
Accession Number
2014864243
PMID
Title
Sex- and strain-specific effects of mitochondrial uncoupling on age-related
metabolic diseases in high-fat diet-fed mice.
Source
Aging Cell. 21(2) (no pagination), 2022. Article Number: e13539. Date of
Publication: February 2022.
Author
Goedeke L.; Murt K.N.; Di Francesco A.; Camporez J.P.; Nasiri A.R.; Wang Y.;
Zhang X.-M.; Cline G.W.; de Cabo R.; Shulman G.I.
Author NameID
Shulman, Gerald I.; ORCID: https://orcid.org/0000-0003-1529-5668
Institution
(Goedeke, Camporez, Nasiri, Wang, Zhang, Cline, Shulman) Department of Internal
Medicine, Yale School of Medicine, New Haven, CT, United States
(Murt, Di Francesco, de Cabo) Translational Gerontology Branch, Intramural
Research Program, National Institute on Aging, NIH, Baltimore, MD, United States
(Camporez) Department of Physiology, Ribeirao Preto School of Medicine,
University of Sao Paulo, Sao Paulo, Brazil
(Shulman) Department of Cellular and Molecular Physiology, Yale School of
Medicine, New Haven, CT, United States
Publisher
Subject Headings
aged
aging
animal experiment
animal tissue
antioxidant activity
article
aspartate aminotransferase blood level
body composition
body temperature
body weight change
C57BL 6 mouse
cancer incidence
conjugation
controlled release formulation
controlled study
drug tolerability
energy expenditure
fat mass
female
fluid intake
food intake
gluconeogenesis
glucose infusion
hepatitis
insulin resistance
insulin sensitivity
lean body weight
*lifespan
*lipid diet
lipid liver level
lipid peroxidation
liver mitochondrion
longevity
male
*metabolic disorder
mitochondrial biogenesis
morbidity
mouse
nonhuman
*oxidative phosphorylation uncoupling
oxidative stress
proof of concept
protein carbonylation
survival rate
*therapeutic index
*antioxidant/po [Oral Drug Administration]
*antioxidant/pd [Pharmacology]
ceramide/ec [Endogenous Compound]
diacylglycerol/ec [Endogenous Compound]
protein kinase C epsilon/ec [Endogenous Compound]
unclassified drug
*controlled release mitochondrial protonophore/po [Oral Drug Administration]
*controlled release mitochondrial protonophore/pd [Pharmacology]
Candidate Terms
*controlled release mitochondrial protonophore / *oral drug administration /
*pharmacology [drug term]
Drug Index Terms
alanine aminotransferase / endogenous compound; *antioxidant / *oral drug
administration / *pharmacology; aspartate aminotransferase / endogenous compound;
ceramide / endogenous compound; diacylglycerol / endogenous compound; glucose /
endogenous compound; protein kinase C epsilon / endogenous compound;
triacylglycerol / endogenous compound; unclassified drug
Other Index Terms
aged; aging; alanine aminotransferase blood level; animal experiment; animal
tissue; antioxidant activity; Article; aspartate aminotransferase blood level; body
composition; body temperature; body weight change; C57BL 6 mouse; cancer incidence;
chronic liver disease; conjugation; controlled release formulation; controlled
study; *diet-induced obesity; drug tolerability; energy expenditure; fat mass;
fatty acid oxidation; female; fluid intake; food intake; gluconeogenesis; glucose
infusion; hepatitis; insulin resistance; insulin sensitivity; lean body weight;
*lifespan; *lipid diet; lipid liver level; lipid peroxidation; liver cell
carcinoma; liver mitochondrion; longevity; male; *metabolic disorder; mitochondrial
biogenesis; morbidity; mouse; nonhuman; *oxidative phosphorylation uncoupling;
oxidative stress; proof of concept; protein carbonylation; survival rate;
*therapeutic index; triacylglycerol blood level
Abstract
Mild uncoupling of oxidative phosphorylation is an intrinsic property of all
mitochondria and may have evolved to protect cells against the production of
damaging reactive oxygen species. Therefore, compounds that enhance mitochondrial
uncoupling are potentially attractive anti-aging therapies; however, chronic
ingestion is associated with a number of unwanted side effects. We have previously
developed a controlled-release mitochondrial protonophore (CRMP) that is
functionally liver-directed and promotes oxidation of hepatic triglycerides by
causing a subtle sustained increase in hepatic mitochondrial inefficiency. Here, we
sought to leverage the higher therapeutic index of CRMP to test whether mild
mitochondrial uncoupling in a liver-directed fashion could reduce oxidative damage
and improve age-related metabolic disease and lifespan in diet-induced obese mice.
Oral administration of CRMP (20 mg/[kg-day] x 4 weeks) reduced hepatic lipid
content, protein kinase C epsilon activation, and hepatic insulin resistance in
aged (74-week-old) high-fat diet (HFD)-fed C57BL/6J male mice, independently of
changes in body weight, whole-body energy expenditure, food intake, or markers of
hepatic mitochondrial biogenesis. CRMP treatment was also associated with a
significant reduction in hepatic lipid peroxidation, protein carbonylation, and
inflammation. Importantly, long-term (49 weeks) hepatic mitochondrial uncoupling
initiated late in life (94-104 weeks), in conjugation with HFD feeding, protected
mice against neoplastic disorders, including hepatocellular carcinoma (HCC), in a
strain and sex-specific manner. Taken together, these studies illustrate the
complex variation of aging and provide important proof-of-concept data to support
further studies investigating the use of liver-directed mitochondrial uncouplers to
promote healthy aging in humans.Copyright © 2022 The Authors. Aging Cell published
by Anatomical Society and John Wiley & Sons Ltd.
sid=OVID:embase&id=pmid:35088525&id=doi:10.1111%2Facel.13539&issn=1474-
9718&isbn=&volume=21&issue=2&spage=e13539&pages=&date=2022&title=Aging+Cell&atitle=
Sex-+and+strain-specific+effects+of+mitochondrial+uncoupling+on+age-
related+metabolic+diseases+in+high-fat+diet-fed+mice&aulast=Goedeke&pid=%3Cauthor
%3EGoedeke+L.%3BMurt+K.N.%3BDi+Francesco+A.%3BCamporez+J.P.%3BNasiri+A.R.%3BWang+Y.
%3BZhang+X.-M.%3BCline+G.W.%3Bde+Cabo+R.%3BShulman+G.I.%3C%2Fauthor%3E%3CAN
<31>
Accession Number
638736043
Title
Clinical prognosis in non-obese non-alcoholic fatty liver disease.
Source
Hepatology International. Conference: 31st Conference of the Asian Pacific
Association for the Study of the Liver, APASL 2022. Seoul South Korea.
16(Supplement 1) (pp S260-S261), 2022. Date of Publication: July 2022.
Author
Iwaki M.; Kessoku T.; Kobayashi T.; Nogami A.; Honda Y.; Yoneda M.; Saito S.;
Nakajima A.
Institution
(Iwaki, Kessoku, Kobayashi, Nogami, Honda, Yoneda, Saito, Nakajima) Department of
Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama city,
Japan
Publisher
Springer
Subject Headings
adult
body mass
cancer patient
*cancer prognosis
cancer staging
carcinogenesis
conference abstract
controlled study
female
fibrosis
follow up
gene expression
human
incidence
inflammation
liver cell
liver dysfunction
male
mortality
multicenter study
obese patient
obesity
*prognosis
risk assessment
bilirubin
endogenous compound
Drug Index Terms
bilirubin; endogenous compound; high density lipoprotein
Other Index Terms
adult; alanine aminotransferase blood level; body mass; cancer patient; *cancer
prognosis; cancer staging; carcinogenesis; cardiovascular disease; conference
abstract; controlled study; female; fibrosis; follow up; gene expression; human;
incidence; inflammation; liver cell; liver cell carcinoma; liver dysfunction; major
clinical study; male; mortality; multicenter study; *nonalcoholic fatty liver;
Nonalcoholic Fatty Liver Disease Activity Score; obese patient; obesity;
*prognosis; risk assessment
Abstract
Objectives: Non-alcoholic fatty liver disease (NAFLD) can progress even in non-
obese subjects. Previous reports have shown that the pathological profile of lean
non-obese NAFLD patients is relatively good, but reports on long-term prognosis are
controversial. Material(s) and Method(s): In this study, we retrospectively
investigated the risk of clinical events and mortality. clinical events include
cardiovascular events, liver-related events, and cancers without hepatocellular
carcinoma. The criteria for non-obese and obese NAFLD were body mass index (BMI)
less than 25 kg/m2 and greater than 25, respectively. Result(s): Of the 255 NAFLD
patients, 66 (25.9%) were non-obese. Compared to obese patients, non-obese patients
had a lower fibrosis stage (0.8 +/- 0.80 vs 1.2 +/- 0.91; P = 0.004). There was no
difference in each pathological finding: steatosis, hepatocyte ballooning,
inflammation and NAFLD activity score. In addition, non-obese NAFLD patients tended
to have significantly lower ALT, Cre, bilirubin and higher HDL levels. After a
median follow-up of 9.7 years, 3 patients (4.5%) in the non-obese group and 5
patients (7.6%) in the obese group died. 12 patients (18.2%) in the non-obese group
and 29 patients (15.3%) in the obese group had clinical events, which tended to be
more frequent in the non-obese group (P = 0.67). After the first 10 years of
follow-up, the clinical event rate tended to be higher in the obese group, but
after that, the clinical event rate was higher in the non-obese group. The non-
obese group was characterized by a higher incidence of carcinogenesis, with 9 of
the 12 patients experiencing carcinogenesis. Conclusion(s): Long-term follow-up of
more than 10 years suggests that non-obese NAFLD patients have a higher risk of
developing clinical events, mainly carcinogenesis. This is a single-center analysis
and needs to be validated in multiple centers.
S261&date=2022&title=Hepatology+International&atitle=Clinical+prognosis+in+non-
obese+non-alcoholic+fatty+liver+disease&aulast=Iwaki&pid=%3Cauthor%3EIwaki+M.
%3BKessoku+T.%3BKobayashi+T.%3BNogami+A.%3BHonda+Y.%3BYoneda+M.%3BSaito+S.
%3BNakajima+A.%3C%2Fauthor%3E%3CAN%3E638736043%3C%2FAN%3E%3CDT
<32>
Accession Number
2018830434
Title
EPIDEMIOLOGY AND PREVALENCE OF LEAN NON-ALCOHOLIC FATTY LIVER DISEASE AND
ASSOCIATED CIRRHOSIS IN THE UNITED STATES: A POPULATION-BASED STUDY.
Source
Gastroenterology. Conference: DDW 2022. San Diego United States. 162(7
Supplement) (pp S-13), 2022. Date of Publication: May 2022.
Author
Almomani A.; Albakri A.A.; Alkhayyat M.; Onwuzo S.; Krishtopaytis E.; Boustany
A.; Kumar P.; Alshaikh D.; Hitawala A.A.; Asaad I.
Publisher
W.B. Saunders
Subject Headings
adult
age
alcohol liver disease
autoimmune hepatitis
biliary cirrhosis
body mass
cancer patient
chronic viral hepatitis
cohort analysis
complication
conference abstract
controlled study
coronary artery disease
cystic fibrosis
diabetes mellitus
dyslipidemia
electronic health record
esophagus varices
female
health care system
hemochromatosis
human
hypertension
*liver cirrhosis
male
obesity
outcome assessment
*prevalence
race
risk assessment
risk factor
smoking
sociology
Systematized Nomenclature of Medicine
*United States
Wilson disease
alpha 1 antitrypsin
endogenous compound
Drug Index Terms
alpha 1 antitrypsin; endogenous compound
Other Index Terms
acute coronary syndrome; adult; age; alcohol liver disease; alpha 1 antitrypsin
deficiency; autoimmune hepatitis; biliary cirrhosis; body mass; cancer patient;
chronic viral hepatitis; cohort analysis; complication; conference abstract;
controlled study; coronary artery disease; cystic fibrosis; data analysis software;
diabetes mellitus; dyslipidemia; electronic health record; esophagus varices;
female; health care system; hemochromatosis; human; hypertension; liver cell
carcinoma; *liver cirrhosis; major clinical study; male; metabolic syndrome X; non
insulin dependent diabetes mellitus; *nonalcoholic fatty liver; obesity; outcome
assessment; *prevalence; race; risk assessment; risk factor; smoking; sociology;
Systematized Nomenclature of Medicine; *United States; Wilson disease
Abstract
Backgrounds and Aims Non-alcoholic fatty liver disease (NAFLD) is the leading
cause for chronic liver diseases in the United States with a prevalence of 21%.
NAFLD is closely linked to obesity in which insulin resistance drives the process.
A subset of NAFLD patients express a normal or low body mass index (BMI) of < 25
kg/m2 (Lean NAFLD, or L-NAFLD) has been increasingly recognized with a global
prevalence of ~7%. Our aim is to compare L-NAFLD to the obesity-associated NAFLD
(O-NAFLD) in the United States in terms of prevalence, potential risk factors,
liver-related complications and coronary artery disease outcomes Methodology A
multi-center database (Explorys Inc.) of electronic health records of 26 healthcare
systems, 360 hospitals and ~80 million patients across the U.S. was utilized for
this study. A cohort of patients with a SNOMED-CT diagnosis of "Non-Alcoholic Fatty
Liver" between 1999-2021 was identified. Subsequently, two sub-cohorts of NAFLD
patients were identified; those with BMI <25 kg/m2 (L-NAFLD group) and those with
BMI >30 kg/ m2 (O-NAFLD group). We excluded all patients with age <18 years,
chronic viral hepatitis, hemochromatosis, Wilson's disease, biliary cirrhosis,
alcoholic liver disease, cystic fibrosis, alpha-1-antitrypsin deficiency, and
autoimmune hepatitis. Statistical Package for Social Sciences (SPSS version 25, IBM
Corp) was used for statistical analysis, and for all analyses, a 2-sided p-value of
<0.05 was considered statistically significant. Multivariate analysis was performed
to adjust for multiple factors including age, sex, race, cirrhosis, hepatocellular
carcinoma, acute coronary syndrome, smoking, esophageal varices and metabolic
syndrome Results Among the 68,892,260 individuals screened, there were a total of
3410 individuals with NAFLD with a prevalence rate of 4 per 100,000, of which 430
(~12%) had L-NAFLD with an overall prevalence of 0.6 per 100,000. The baseline
characteristics of study population is shown in Table 1. Comparing to those
without, L-NAFLD patients tended to be older (OR 2.16), females (OR 1.28), smokers
(OR 4.67) and of Asian race (OR 2.12). Interestingly, L-NAFLD patients were also
more likely to have Acute Coronary Syndromes (ACS) (OR 30.00) and metabolic
syndrome (type 2 diabetes mellitus, hypertension, and dyslipidemia) (OR 2.31)
despite the normal or low BMI (Table 2a). Risks for esophageal varices and
hepatocellular carcinoma (HCC) were high in both O-NAFLD and L-NAFLD cirrhosis
patients (Table 2b) Conclusion This is the largest population-based study to assess
the prevalence of L-NAFLD in the U.S. Smoking history, Asian race and metabolic
syndrome (type 2 diabetes mellitus, hypertension, and dyslipidemia) seemed to offer
the highest risk for the development of LNAFLD. Similar to O-NAFLD, L-NAFLD is
associated with higher risks of esophageal varices, HCC and coronary artery
diseases. (Table Presented)Copyright © 2022, AGA Institute.
sid=OVID:embase&id=pmid:&id=doi:10.1016%2FS0016-5085%252822%252960034-9&issn=0016-
5085&isbn=&volume=162&issue=7+Supplement&spage=S&pages=S-
13&date=2022&title=Gastroenterology&atitle=EPIDEMIOLOGY+AND+PREVALENCE+OF+LEAN+NON-
ALCOHOLIC+FATTY+LIVER+DISEASE+AND+ASSOCIATED+CIRRHOSIS+IN+THE+UNITED+STATES
%3A+A+POPULATION-BASED+STUDY&aulast=Almomani&pid=%3Cauthor%3EAlmomani+A.
%3BAlbakri+A.A.%3BAlkhayyat+M.%3BOnwuzo+S.%3BKrishtopaytis+E.%3BBoustany+A.
%3BKumar+P.%3BAlshaikh+D.%3BHitawala+A.A.%3BAsaad+I.%3C%2Fauthor%3E%3CAN
%3E2018830434%3C%2FAN%3E%3CDT%3EConference+Abstract%3C%2FDT%3E
<33>
Accession Number
2015108053
Title
PI3Kgamma promotes obesity-associated hepatocellular carcinoma by regulating
metabolism and inflammation.
Source
JHEP Reports. 3(6) (no pagination), 2021. Article Number: 100359. Date of
Author
Becattini B.; Breasson L.; Sardi C.; Zani F.; Solinas G.
Author NameID
Breasson, Ludovic; ORCID: https://orcid.org/0000-0003-2168-976X
Solinas, Giovanni; ORCID: https://orcid.org/0000-0002-0140-2621
Institution
(Becattini, Breasson, Sardi, Solinas) The Wallenberg Laboratory, Department of
Molecular and Clinical Medicine at Institute of Medicine, University of Gothenburg,
Sahlgrenska University Hospital, Gothenburg, Sweden
(Zani) The Francis Crick Institute, London, United Kingdom
Publisher
Elsevier B.V.
Subject Headings
adult
animal cell
animal experiment
animal model
animal tissue
article
cancer inhibition
cell proliferation
controlled study
endothelium cell
enzyme inhibition
fatty liver
hematopoietic cell
histopathology
*inflammation
insulin level
insulin sensitivity
insulinemia
leukocyte
lipid liver level
liver cell
male
metabolic stress
*metabolism
mouse
neutrophil
neutrophil chemotaxis
nonhuman
ob/ob mouse
obesogenic diet
phenotype
protein expression
tumor cell
tumor number
cytokine/ec [Endogenous Compound]
diethylnitrosamine
*phosphatidylinositol 3 kinase gamma/ec [Endogenous Compound]
Drug Index Terms
cytokine / endogenous compound; diethylnitrosamine; *phosphatidylinositol 3
kinase gamma / *endogenous compound
Other Index Terms
adult; animal cell; animal experiment; animal model; animal tissue; Article;
cancer inhibition; cell proliferation; controlled study; *diet-induced obesity;
*disease association; endothelium cell; enzyme inhibition; fatty liver;
hematopoietic cell; histopathology; *inflammation; insulin level; insulin
sensitivity; insulinemia; leukocyte; lipid liver level; liver cell; *liver cell
carcinoma; male; metabolic stress; *metabolism; mouse; neutrophil; neutrophil
chemotaxis; nonhuman; ob/ob mouse; obesogenic diet; phenotype; protein expression;
tumor cell; tumor number
Abstract
Background & Aims: Phosphatidylinositides-3 kinases (PI3Ks) are promising drug
targets for cancer therapy, but blockage of PI3K-AKT signalling causes
hyperglycaemia, hyperinsulinaemia, and liver damage in patients, and hepatocellular
carcinoma (HCC) in mice. There are 4 PI3Ks: PI3Kalpha, PI3Kbeta, PI3Kdelta, and
PI3Kgamma. The role of PI3Kgamma in HCC is unknown. Method(s): We performed
histopathological, metabolic, and molecular phenotyping of mice with genetic
ablation of PI3Kgamma using models where HCC was initiated by the carcinogen
diethylnitrosamine (DEN) and promoted by dietary or genetic obesity (ob/ob). The
role of PI3Kgamma in leucocytes was investigated in mice lacking PI3Kgamma in
haematopoietic and endothelial cells. Result(s): Loss of PI3Kgamma had no effects
on the development of DEN-induced HCC in lean mice. However, in mice injected with
DEN and placed on an obesogenic diet, PI3Kgamma ablation reduced tumour growth,
which was associated with reduced insulinaemia, steatosis, and expression of
inflammatory cytokines. ob/ob mice lacking PI3Kgamma, and mice with diet-induced
obesity lacking PI3Kgamma in leucocytes and endothelial cells did not display
improved insulin sensitivity, steatosis, metabolic inflammation, or reduced tumour
growth. However, these mice showed a reduced number of tumours, reduced liver
infiltration by neutrophils, and reduced hepatocyte proliferation acutely induced
by DEN. Conclusion(s): Loss of PI3Kgamma reduces tumour development in obesity-
promoted HCC through multiple cell types and mechanisms that include improved
insulinaemia, steatosis, and metabolic inflammation as well as the regulation of
acute neutrophil infiltration and compensatory hepatocyte proliferation. PI3Kgamma-
selective inhibition may represent a novel therapeutic approach to reduce HCC
initiation and slow HCC progression. Lay summary: Class-1 phosphatidylinositides-3
kinases (PI3Ks) are critical targets in cancer therapy, but complete inhibition of
all isoforms causes liver damage, hyperglycaemia, and insulinaemia. Here we show
that selective ablation of the PI3Kgamma isoform dampens tumour initiation and
growth in a mouse model of carcinogen-initiated and obesity-promoted hepatocellular
carcinoma (HCC). The effect of PI3Kgamma ablation on reduced tumour growth was
explained by reduced tumour cell proliferation, which was associated with reduced
insulin levels, liver lipids, and reduced expression of tumour-promoting cytokines.
PI3Kgamma ablation in leucocytes of obese mice had no effects on tumour size.
However, it reduced tumour number in association with reduced carcinogen-induced
neutrophil infiltration and hepatocyte proliferation in livers of obese mice.
Inhibition of PI3Kgamma may thus reduce HCC initiation and growth in obese subjects
by a mechanism involving reduced metabolic stress and insulinaemia and reduced
carcinogen-induced neutrophil infiltration to the fatty liver.Copyright © 2021 The
Author(s)
sid=OVID:embase&id=pmid:&id=doi:10.1016%2Fj.jhepr.2021.100359&issn=2589-
5559&isbn=&volume=3&issue=6&spage=100359&pages=&date=2021&title=JHEP+Reports&atitle
=PI3Kgamma+promotes+obesity-
associated+hepatocellular+carcinoma+by+regulating+metabolism+and+inflammation&aulas
t=Becattini&pid=%3Cauthor%3EBecattini+B.%3BBreasson+L.%3BSardi+C.%3BZani+F.
%3BSolinas+G.%3C%2Fauthor%3E%3CAN%3E2015108053%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<34>
Accession Number
2014075968
Title
Excess Body Weight and Metabolic (Dysfunction)-Associated Fatty Liver Disease
(MAFLD).
Source
Visceral Medicine. 37(4) (pp 273-280), 2021. Date of Publication: 01 Aug 2021.
Author
Roeb E.
Institution
(Roeb) Gastroenterology, Justus Liebig University, University Hospital Giesen,
Giesen, Germany
Publisher
S. Karger AG
Subject Headings
*body weight
diabetes mellitus
Europe
fibrogenesis
human
lipid metabolism
lipodystrophy
liver cirrhosis
liver fibrosis
nomenclature
obesity
pathogenesis
physical activity
prevalence
review
virus hepatitis
amiodarone
methotrexate
tamoxifen
Drug Index Terms
amiodarone; methotrexate; tamoxifen
Other Index Terms
*body weight; diabetes mellitus; Europe; fibrogenesis; human; lifestyle
modification; lipid metabolism; lipodystrophy; liver cell carcinoma; liver
cirrhosis; liver fibrosis; *metabolic fatty liver; nomenclature; non insulin
dependent diabetes mellitus; nonalcoholic steatohepatitis; obesity; pathogenesis;
physical activity; prevalence; Review; virus hepatitis
Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) describes a continuum of
liver abnormalities from simple nonalcoholic fatty liver (NAFL) to nonalcoholic
fatty liver hepatitis or steatohepatitis (NASH) to NASH fibrosis. It has a variable
course, but just like alcoholic fatty liver disease, it can lead to liver cirrhosis
and cancer (hepatocellular carcinoma). Summary: NAFLD is a clinical entity
characterized by the presence of liver steatosis, which affects at least 5% of
hepatocytes. Affected are people who consume little or no alcohol and who have no
secondary cause of liver steatosis such as viral hepatitis, drug intake (e.g.,
tamoxifen, amiodarone, methotrexate, etc.), or lipodystrophy. NAFLD is, nowadays,
the most common liver disease in Europe, with an estimated prevalence of 25%. The
currently widely recognized recommendation for the therapy of NAFLD is a lifestyle
modification with the goal of weight loss. Although no drugs are currently approved
for the treatment of NAFLD, several candidates are in clinical trials. Besides
weight loss and physical activity, corresponding single active ingredients or
combination therapies are intended to stop the progression of the disease and, in
the best case, reverse it. The newly propagated name MAFLD (metabolic-associated
fatty liver disease) should indicate that the disease is associated with metabolic
disorders. The term MAFLD also implies multiple overlapping causes and drivers of
this soaring disease. Key Messages: The prevalence of NAFLD continues to rise
worldwide. NAFLD, NASH, and fibrosis in NAFLD occur predominantly in patients with
obesity and type 2 diabetes (T2DM) or else precede these conditions. The
progression of NAFLD is highly dependent on changes in glucose, lipid metabolism,
and fibrogenesis. A new definition and nomenclature of fatty liver disease,
"metabolic associated fatty liver disease"(MAFLD), should be discussed carefully,
since around 40% of the global population with NAFLD are classified as non-obese
and almost 1/5 as lean. Since the pathogenesis of fatty liver disease, obesity, and
glucose and lipid metabolism diseases are very closely related, it is important to
continue to look for mechanisms that these diseases have in common and develop new
therapeutic approaches.Copyright © 2021 The Author(s) Published by S. Karger AG,
Basel.
280&date=2021&title=Visceral+Medicine&atitle=Excess+Body+Weight+and+Metabolic+
%28Dysfunction%29-Associated+Fatty+Liver+Disease+%28MAFLD%29&aulast=Roeb&pid=
%3Cauthor%3ERoeb+E.%3C%2Fauthor%3E%3CAN%3E2014075968%3C%2FAN%3E%3CDT%3EReview%3C
%2FDT%3E
<35>
Accession Number
2013091599
Title
Impact of MAFLD on HBV-related stage 0/A hepatocellular carcinoma after curative
resection.
Source
Journal of Personalized Medicine. 11(8) (no pagination), 2021. Article Number:
684. Date of Publication: August 2021.
Author
Lin Y.-P.; Lin S.-H.; Wang C.-C.; Lin C.-C.; Chen D.-W.; Chuang C.-H.; Huang P.-
Y.; Hung C.-H.; Yang S.-Y.; Cho W.-R.; Chen Y.-S.; Tsai M.-C.
Author NameID
Huang, Pao-Yuan; ORCID: https://orcid.org/0000-0002-6666-944X
Cho, Wei-Ru; ORCID: https://orcid.org/0000-0001-9232-5424
Chuang, Ching-Hui; ORCID: https://orcid.org/0000-0001-8366-8986
Tsai, Ming-Chao; ORCID: https://orcid.org/0000-0002-3613-2051
Institution
(Lin, Chen, Tsai) School of Medicine, Chung-Shan Medical University, Taichung
40201, Taiwan (Republic of China)
(Lin, Huang, Hung, Yang, Cho) Division of Hepato-Gastroenterology, Department of
Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University
College of Medicine, Kaohsiung 83301, Taiwan (Republic of China)
(Wang, Lin) Liver Transplantation Center, Department of Surgery, Kaohsiung Chang
Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301,
Taiwan (Republic of China)
(Chen) Center for Translational Research in Biomedical Sciences, Liver
Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial
Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
(Republic of China)
(Chuang) Department of Nursing, Meiho University, Pingtung 91202, Taiwan
(Republic of China)
(Tsai) Graduate Institute of Clinical Medical Sciences, Chang Gung University
College of Medicine, Kaohsiung 83301, Taiwan (Republic of China)
Publisher
MDPI
Subject Headings
adult
alcohol consumption
article
biochemical recurrence free survival
cancer prognosis
cancer recurrence
cancer survival
Child Pugh score
chronic hepatitis B
clinical outcome
controlled study
estimated glomerular filtration rate
female
follow up
*hepatitis B
*Hepatitis B virus
histopathology
HOMA index
human
human tissue
immunohistochemistry
liver cirrhosis
*liver resection
male
nonhuman
obesity
outcome assessment
overall survival
platelet count
recurrence free survival
retrospective study
thrombocyte
tumor differentiation
tumor recurrence
tumor volume
waist circumference
albumin/ec [Endogenous Compound]
alpha fetoprotein/ec [Endogenous Compound]
bilirubin/ec [Endogenous Compound]
creatinine/ec [Endogenous Compound]
hepatitis B surface antigen/ec [Endogenous Compound]
hepatitis B(e) antigen/ec [Endogenous Compound]
hepatitis C antibody/ec [Endogenous Compound]
high density lipoprotein cholesterol/ec [Endogenous Compound]
COBAS Taqman
Candidate Terms
COBAS TaqMan [device term]
Drug Index Terms
alanine aminotransferase / endogenous compound; albumin / endogenous compound;
alpha fetoprotein / endogenous compound; aspartate aminotransferase / endogenous
compound; bilirubin / endogenous compound; C reactive protein / endogenous
compound; creatinine / endogenous compound; hepatitis B surface antigen /
endogenous compound; hepatitis B(e) antigen / endogenous compound; hepatitis C
antibody / endogenous compound; high density lipoprotein cholesterol / endogenous
compound; triacylglycerol / endogenous compound
Other Index Terms
adult; alcohol consumption; Article; biochemical recurrence free survival; cancer
prognosis; cancer recurrence; cancer survival; Child Pugh score; chronic hepatitis
B; clinical outcome; controlled study; cross-sectional study; estimated glomerular
filtration rate; female; follow up; *hepatitis B; *Hepatitis B virus;
histopathology; HOMA index; human; human tissue; immunohistochemistry; *liver cell
carcinoma; liver cirrhosis; *liver resection; liver transplantation; major clinical
study; male; *metabolic fatty liver; non insulin dependent diabetes mellitus;
nonhuman; obesity; outcome assessment; overall survival; platelet count; recurrence
free survival; retrospective study; thrombocyte; tumor differentiation; tumor
recurrence; tumor volume; waist circumference
Abstract
Backgrounds and Aim: Metabolic-associated fatty liver dis-ease (MAFLD) is a novel
term proposed in 2020 to avoid the exclusion of certain subpopulations, though the
application of this term in the real world is very limited. Here, we aimed to
evaluate the impact of MAFLD on hepatitis B virus (HBV)-related hepatocellular
carcinoma (HCC) after curative resection. Method(s): Patients with chronic
hepatitis B (CHB)-related HCC who received hepatectomy between January 2010 and
December 2019 were consecutively selected. The association between histologically
proven concurrent MAFLD and clinical outcomes were retrospectively analyzed.
Result(s): Among the 812 eligible patients with CHB-related HCC, 369 (45.4%) were
diagnosed with concurrent MAFLD. After a mean follow-up of 65 months, 303 patients
(37.3%) developed HCC recurrence, 111 (13.7%) died, and 12 (1.5%) received liver
transplantation. Although no differences in the incidences of HCC recurrence (HR:
0.902, 95% CI: 0.719-1.131, p = 0.370) and death or liver transplantation (HR:
0.743, 95% CI: 0.518-1.006, p = 0.107) were observed between patients with and
without MAFLD in multivariate analysis, the patients with MAFLD tended to achieve
better recurrent-free survival compared to patients without MAFLD. Notably, lean
MAFLD (BMI < 23 kg/m2) was a relative risk factor for tumor recurrence (HR: 2.030,
95% CI: 1.117-3.690, p = 0.020) among patients with MAFLD. Conclusion(s): The
overall prognosis in HBV-related early-stage HCC, in terms of HCC recurrence and
death or liver transplantation, was not significantly different between patients
with and without MAFLD. Among patients with MALFD, lean-MAFLD was a risk factor for
HCC recurrence. Further studies are warranted to validate these results.Copyright ©
2021 by the authors.
sid=OVID:embase&id=pmid:&id=doi:10.3390%2Fjpm11080684&issn=2075-
4426&isbn=&volume=11&issue=8&spage=684&pages=&date=2021&title=Journal+of+Personaliz
ed+Medicine&atitle=Impact+of+MAFLD+on+HBV-
related+stage+0%2FA+hepatocellular+carcinoma+after+curative+resection&aulast=Lin&pi
d=%3Cauthor%3ELin+Y.-P.%3BLin+S.-H.%3BWang+C.-C.%3BLin+C.-C.%3BChen+D.-W.
%3BChuang+C.-H.%3BHuang+P.-Y.%3BHung+C.-H.%3BYang+S.-Y.%3BCho+W.-R.%3BChen+Y.-S.
%3BTsai+M.-C.%3C%2Fauthor%3E%3CAN%3E2013091599%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<36>
Accession Number
2011566881
PMID
Title
The interaction between the gut microbiota and dietary carbohydrates in
nonalcoholic fatty liver disease.
Source
Experimental and Molecular Medicine. 53(5) (pp 809-822), 2021. Date of
Author
Park G.; Jung S.; Wellen K.E.; Jang C.
Author NameID
Jang, Cholsoon; ORCID: https://orcid.org/0000-0001-6651-4213
Institution
(Park, Jung, Jang) Department of Biological Chemistry, Chao Family Comprehensive
Cancer Center, University of California Irvine, Irvine, CA, United States
(Wellen) Department of Cancer Biology, University of Pennsylvania Perelman School
of Medicine, Philadelphia, PA, United States
Publisher
Springer Nature
Subject Headings
apoptosis
*carbohydrate diet
carbohydrate metabolism
cell proliferation
cell viability
cholesterol synthesis
citric acid cycle
dietary fiber
disease association
disease severity
down regulation
enzyme localization
enzyme phosphorylation
enzyme stability
fructose metabolism
glucose transport
glycolysis
histone acetylation
human
insulin resistance/et [Etiology]
insulin sensitivity
*intestine flora
lipid storage
lipogenesis
lipotoxicity/et [Etiology]
liver cell
liver cirrhosis/et [Etiology]
nonhuman
nuclear localization signal
obesity
oxidative stress
pathogenesis
prevalence
prognosis
protein expression
review
risk factor
ubiquitination
upregulation
acetate coenzyme A ligase/ec [Endogenous Compound]
acetyl coenzyme A/ec [Endogenous Compound]
fructose
glucose
ketohexokinase/ec [Endogenous Compound]
monounsaturated fatty acid/ec [Endogenous Compound]
saturated fatty acid/ec [Endogenous Compound]
sterol regulatory element binding protein 1/ec [Endogenous Compound]
ubiquitin/ec [Endogenous Compound]
unclassified drug
ketohexokinase c/ec [Endogenous Compound]
Candidate Terms
ketohexokinase c / endogenous compound [drug term]
Drug Index Terms
acetate coenzyme A ligase / endogenous compound; acetyl coenzyme A / endogenous
compound; cholesterol / endogenous compound; fructose; glucose; ketohexokinase /
endogenous compound; monounsaturated fatty acid / endogenous compound; saturated
fatty acid / endogenous compound; sterol regulatory element binding protein 1 /
endogenous compound; triacylglycerol / endogenous compound; ubiquitin / endogenous
compound; unclassified drug
Other Index Terms
apoptosis; *carbohydrate diet; carbohydrate metabolism; cell proliferation; cell
viability; cholesterol blood level; cholesterol synthesis; citric acid cycle;
dietary fiber; disease association; disease severity; down regulation; enzyme
localization; enzyme phosphorylation; enzyme stability; fructose metabolism;
glucose transport; glycolysis; histone acetylation; human; insulin resistance /
etiology; insulin sensitivity; *intestine flora; lipid storage; lipogenesis;
lipotoxicity / etiology; liver cell; liver cirrhosis / etiology; non insulin
dependent diabetes mellitus; *nonalcoholic fatty liver / *etiology; nonhuman;
nuclear localization signal; obesity; oxidative stress; pathogenesis; prevalence;
prognosis; protein expression; Review; risk factor; triacylglycerol blood level;
ubiquitination; upregulation
Abstract
Imbalance between fat production and consumption causes various metabolic
disorders. Nonalcoholic fatty liver disease (NAFLD), one such pathology, is
characterized by abnormally increased fat synthesis and subsequent fat accumulation
in hepatocytes1,2. While often comorbid with obesity and insulin resistance, this
disease can also be found in lean individuals, suggesting specific metabolic
dysfunction2. NAFLD has become one of the most prevalent liver diseases in adults
worldwide, but its incidence in both children and adolescents has also markedly
increased in developed nations3,4. Progression of this disease into nonalcoholic
steatohepatitis (NASH), cirrhosis, liver failure, and hepatocellular carcinoma in
combination with its widespread incidence thus makes NAFLD and its related
pathologies a significant public health concern. Here, we review our understanding
of the roles of dietary carbohydrates (glucose, fructose, and fibers) and the gut
microbiota, which provides essential carbon sources for hepatic fat synthesis
during the development of NAFLD.Copyright © 2021, The Author(s).
sid=OVID:embase&id=pmid:34017059&id=doi:10.1038%2Fs12276-021-00614-x&issn=1226-
822&date=2021&title=Experimental+and+Molecular+Medicine&atitle=The+interaction+betw
een+the+gut+microbiota+and+dietary+carbohydrates+in+nonalcoholic+fatty+liver+diseas
e&aulast=Park&pid=%3Cauthor%3EPark+G.%3BJung+S.%3BWellen+K.E.%3BJang+C.%3C%2Fauthor
%3E%3CAN%3E2011566881%3C%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<37>
Accession Number
2010481090
PMID
Title
The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with
individual and forecasting analysis, 1995-2040.
Source
Hepatology International. 15(2) (pp 366-379), 2021. Date of Publication: April
2021.
Author
Ito T.; Ishigami M.; Zou B.; Tanaka T.; Takahashi H.; Kurosaki M.; Maeda M.; Thin
K.N.; Tanaka K.; Takahashi Y.; Itoh Y.; Oniki K.; Seko Y.; Saruwatari J.; Kawanaka
M.; Atsukawa M.; Hyogo H.; Ono M.; Ogawa E.; Barnett S.D.; Stave C.D.; Cheung R.C.;
Fujishiro M.; Eguchi Y.; Toyoda H.; Nguyen M.H.
Author NameID
Nguyen, Mindie H.; ORCID: https://orcid.org/0000-0002-6275-4989
Institution
(Ito, Ishigami, Tanaka, Fujishiro) Department of Gastroenterology and Hepatology,
Nagoya University Graduate School of Medicine, Nagoya, Japan
(Zou, Maeda, Thin, Barnett, Cheung, Nguyen) Division of Gastroenterology and
Hepatology, Department of Medicine, Stanford University Medical Center, 780 Welch
Road, CJ250K, Palo Alto, CA 94304, United States
(Takahashi, Eguchi) Liver Center, Saga University Hospital, Saga, Japan
(Takahashi, Tanaka, Eguchi) Division of Metabolism and Endocrinology, Faculty of
Medicine, Saga University, Saga, Japan
(Kurosaki, Takahashi) Department of Gastroenterology and Hepatology, Musashino
Red Cross Hospital, Tokyo, Japan
(Thin) Yangon Specialty Hospital, Yangon, Myanmar
(Itoh, Seko) Department of Molecular Gastroenterology and Hepatology, Kyoto
Prefectural University of Medicine, Kyoto, Japan
(Oniki, Saruwatari) Division of Pharmacology and Therapeutics, Graduate School of
Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
(Kawanaka) Department of General Internal Medicine 2, Kawasaki Medical School
General Medical Center, Okayama, Japan
(Atsukawa) Division of Gastroenterology and Hepatology, Nippon Medical School,
Tokyo, Japan
(Hyogo) Department of Gastroenterology and Hepatology, JA Hiroshima General
Hospital, Hiroshima, Japan
(Ono) Department of Internal Medicine, Tokyo Women's Medical University Medical
Center East, Tokyo, Japan
(Ogawa) Department of General Internal Medicine, Kyushu University Hospital,
Fukuoka, Japan
(Stave) Lane Medical Library, Stanford University School of Medicine, Palo Alto,
CA, United States
(Cheung) Palo Alto Veterans Affairs Healthcare System, Palo Alto, CA, United
States
(Toyoda) Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital,
Ogaki, Japan
Publisher
Springer
Subject Headings
age distribution
all cause mortality
article
Bayesian network
cancer incidence
clinical feature
clinical outcome
data analysis
data base
diabetes mellitus
*fatty liver/ep [Epidemiology]
Fibrosis-4 Index
forecasting
geographic distribution
human
incidence
income
Japan
lean body weight
liver cell carcinoma/ep [Epidemiology]
medical society
mortality rate
obesity/ep [Epidemiology]
prediction
*prevalence
productivity
publication bias
sex difference
systematic review
trend study
*lean nonalcoholic fatty liver/ep [Epidemiology]
Candidate Terms
*lean nonalcoholic fatty liver / *epidemiology [other term]
Other Index Terms
age distribution; all cause mortality; Article; Bayesian network; cancer
incidence; clinical feature; clinical outcome; data analysis; data base; diabetes
mellitus; *fatty liver / *epidemiology; Fibrosis-4 Index; forecasting; geographic
distribution; human; incidence; income; Japan; lean body weight; liver cell
carcinoma / epidemiology; medical society; mortality rate; *nonalcoholic fatty
liver / *epidemiology; obesity / epidemiology; prediction; *prevalence;
productivity; publication bias; sex difference; systematic review; trend study
Abstract
Background: NAFLD is increasing in Asia including Japan, despite its lower
obesity rate than the West. However, NAFLD can occur in lean people, but data are
limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on
lean NAFLD. Method(s): We searched PubMed, Cochrane Library, EMBASE, Web of
Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and
included 73 eligible full-text original research studies (n = 258,531). We used
random-effects model for pooled estimates, Bayesian modeling for trend and
forecasting, contacted authors for individual patient data and analyzed 14,887
(7752 NAFLD; 7135 non-NAFLD-8 studies) patients. Result(s): The overall NAFLD
prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001),
and increased over time (p = 0.015), but not by per-person income or gross
prefectural productivity, which increased by 0.64% per year (1983-2012) and is
forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC,
and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively.
Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the
NAFLD population, with lean NAFLD persons being older and with a higher all-cause
mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02).
Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality,
but not lean NAFLD. Conclusion(s): NAFLD prevalence has increased in Japan and may
affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the
NAFLD population, were older, and had higher mortality.Copyright © 2021, Asian
Pacific Association for the Study of the Liver.
379&date=2021&title=Hepatology+International&atitle=The+epidemiology+of+NAFLD+and+l
ean+NAFLD+in+Japan%3A+a+meta-analysis+with+individual+and+forecasting+analysis
%2C+1995-2040&aulast=Ito&pid=%3Cauthor%3EIto+T.%3BIshigami+M.%3BZou+B.%3BTanaka+T.
%3BTakahashi+H.%3BKurosaki+M.%3BMaeda+M.%3BThin+K.N.%3BTanaka+K.%3BTakahashi+Y.
%3BItoh+Y.%3BOniki+K.%3BSeko+Y.%3BSaruwatari+J.%3BKawanaka+M.%3BAtsukawa+M.
%3BHyogo+H.%3BOno+M.%3BOgawa+E.%3BBarnett+S.D.%3BStave+C.D.%3BCheung+R.C.
%3BFujishiro+M.%3BEguchi+Y.%3BToyoda+H.%3BNguyen+M.H.%3C%2Fauthor%3E%3CAN
<38>
Accession Number
2013021896
PMID
Title
Comparison of clinical and metabolic profiles of lean versus non-lean
nonalcoholic fatty liver disease.
Source
Indian Journal of Gastroenterology. 40(4) (pp 380-388), 2021. Date of
Publication: August 2021.
Author
Navarroza A.M.C.; Wong S.N.
Author NameID
Wong, Stephen N.; ORCID: https://orcid.org/0000-0001-8399-3498
Institution
(Navarroza, Wong) Section of Gastroenterology, University of Santo Tomas
Hospital, Manila, Philippines
(Wong) Section of Gastroenterology, Chinese General Hospital and Medical Center,
Manila, Philippines
Publisher
Springer
Subject Headings
adult
article
body mass
diabetes mellitus
female
hepatitis B
human
liver cirrhosis
male
middle aged
retrospective study
albumin/ec [Endogenous Compound]
amiodarone
estrogen
glucocorticoid
tamoxifen
valproic acid
Drug Index Terms
alanine aminotransferase / endogenous compound; albumin / endogenous compound;
amiodarone; estrogen; glucocorticoid; high density lipoprotein cholesterol /
endogenous compound; tamoxifen; valproic acid
Other Index Terms
adult; Article; body mass; cross-sectional study; diabetes mellitus; female;
hepatitis B; human; liver cell carcinoma; liver cirrhosis; major clinical study;
male; metabolic syndrome X; middle aged; *nonalcoholic fatty liver / *diagnosis;
retrospective study
Abstract
Background: Data on nonalcoholic fatty liver disease (NAFLD) in the Philippines
are scarce. We aimed to compare the clinical and biochemical profiles of lean
(BMI<23) vs. non-lean (BMI>=23) NAFLD patients. Method(s): Consecutive patients
diagnosed with NAFLD on ultrasound in two outpatient hepatology clinics from
February 2007-January 2017 were included. Patients with significant alcohol intake,
alternative causes of steatosis, and incomplete data were excluded. Result(s): A
total of 663 patients (57.9% male) were included. Most patients were non-lean
(88.1%) and had an elevated alanine aminotransferase (ALT) (63%). Cirrhosis or
hepatocellular carcinoma (HCC) were already present in 8.4% on initial
consultation. Concomitant hepatitis B was equally common in patients with and
without cirrhosis (20.7% vs. 17.5%; p=0.660) or HCC (17.9% vs. 12.8%; p=0.415).
Independent factors associated with HCC/cirrhosis on initial consultation were
older age (OR=1.038), low albumin (OR=0.428), high BARD score (BMI, AST/ALT ratio,
T2 diabetes mellitus; OR=2.548) and the presence of symptoms (OR=1.808). Compared
to lean NAFLD patients, non-lean patients were more likely to be younger (51.5+/-
14.4 vs. 55+/-14.3; p=0.003), have DM (47.9% vs. 29.1%; p=0.002), hypertension
(57.5% vs. 38%; p=0.001), dyslipidemia (73.1% vs. 54.4%; p=0.001) and metabolic
syndrome (60.3% vs. 30.4%; p<0.0001), abnormal metabolic parameters (LDL-C, HDL-C,
triglycerides, uric acid and FBS), and with elevated ALT (65.2% vs. 46.8%; p=0.002)
and AST (41.1+/-29.6 vs. 35.3+/-28.3; p=0.008). Conclusion(s): The proportion of
lean NAFLD was 11.9%. Although metabolic derangements and its clinical consequences
were present in about a third of lean patients, these were still more common in
non-lean NAFLD. Cirrhosis or HCC were already present in a significant proportion
(8.4%) of NAFLD patients on initial presentation.[Figure not available: see
fulltext.].Copyright © 2021, Indian Society of Gastroenterology.
388&date=2021&title=Indian+Journal+of+Gastroenterology&atitle=Comparison+of+clinica
l+and+metabolic+profiles+of+lean+versus+non-
lean+nonalcoholic+fatty+liver+disease&aulast=Navarroza&pid=%3Cauthor
%3ENavarroza+A.M.C.%3BWong+S.N.%3C%2Fauthor%3E%3CAN%3E2013021896%3C%2FAN%3E%3CDT
<39>
Accession Number
2005543134
PMID
Title
Nonalcoholic Fatty Liver Disease Risk Factors Affect Liver-Related Outcomes After
Direct-Acting Antiviral Treatment for Hepatitis C.
Source
Digestive Diseases and Sciences. 66(7) (pp 2394-2406), 2021. Date of Publication:
July 2021.
Author
Benhammou J.N.; Moon A.M.; Pisegna J.R.; Su F.; Vutien P.; Moylan C.A.; Ioannou
G.N.
Author NameID
Benhammou, Jihane N.; ORCID: https://orcid.org/0000-0003-2442-5145
Institution
(Benhammou) Pfleger Liver Institute, University of California Los Angeles, 200
Medical Plaza, Los Angeles, CA 90095, United States
(Benhammou, Pisegna) Division of Gastroenterology, Hepatology and Parenteral
Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, 11301
Wilshire Blvd., Los Angeles, CA 90073, United States
(Moon, Ioannou) Division of Gastroenterology and Hepatology, The University of
North Carolina at Chapel Hill, 130 Mason Farm Road, Bioinformatics Building
CB#7080, Chapel Hill, NC 27599-7080, United States
(Su, Vutien) Division of Gastroenterology and Hepatology, University of
Washington, Seattle, WA, United States
(Moylan) Division of Gastroenterology, Veterans Affairs Health System, Durham,
NC, United States
(Moylan) Division of Gastroenterology, Duke University Health System, 905 Lasalle
St., Gsrb 1 DUMC 3256, Durham, NC 27710, United States
(Ioannou) Health Service Research and Development, Veterans Affairs Puget Sound
Health Care System, S-111-Gastro, 1660 S. Columbian Way, Seattle, WA 98108, United
States
(Ioannou) Division of Gastroenterology, Veterans Affairs Puget Sound Health Care
System, S-111-Gastro, 1660 S. Columbian Way, Seattle, WA 98108, United States
Publisher
Springer
Subject Headings
adult
adverse outcome
*antiviral therapy
article
body mass
cancer patient
clinical outcome
cohort analysis
controlled study
diabetes mellitus
diabetic patient
female
follow up
*hepatitis C/dt [Drug Therapy]
high risk patient
human
liver cirrhosis
male
middle aged
mortality risk
nonhuman
obese patient
obesity
retrospective study
*risk factor
sustained virologic response
underweight
*antivirus agent/dt [Drug Therapy]
daclatasvir/cb [Drug Combination]
daclatasvir/dt [Drug Therapy]
dasabuvir plus ombitasvir plus paritaprevir plus ritonavir/dt [Drug Therapy]
hemoglobin A1c/ec [Endogenous Compound]
ledipasvir plus sofosbuvir/dt [Drug Therapy]
simeprevir/cb [Drug Combination]
simeprevir/dt [Drug Therapy]
sofosbuvir/cb [Drug Combination]
sofosbuvir/dt [Drug Therapy]
Drug Index Terms
*antivirus agent / *drug therapy; daclatasvir / drug combination / drug therapy;
dasabuvir plus ombitasvir plus paritaprevir plus ritonavir / drug therapy;
hemoglobin A1c / endogenous compound; ledipasvir plus sofosbuvir / drug therapy;
simeprevir / drug combination / drug therapy; sofosbuvir / drug combination / drug
therapy
Other Index Terms
adult; adverse outcome; *antiviral therapy; Article; body mass; cancer patient;
clinical outcome; cohort analysis; controlled study; decompensated liver cirrhosis;
diabetes mellitus; diabetic patient; female; follow up; *hepatitis C / *drug
therapy; high risk patient; human; liver cell carcinoma; liver cirrhosis; major
clinical study; male; middle aged; mortality risk; *nonalcoholic fatty liver;
nonhuman; obese patient; obesity; retrospective study; *risk factor; sustained
virologic response; underweight
Abstract
Introduction: In hepatitis C (HCV) patients, obesity and/or diabetes may increase
the risk of liver-related outcomes. We aimed to determine whether diabetes and/or
obesity are associated with adverse outcomes in direct-acting antiviral (DAA)-
treated HCV patients. Method(s): We conducted a retrospective study of 33,003 HCV-
infected, DAA-treated Veterans between 2013 and 2015. Body mass index was used to
categorize patients into underweight (< 18.5 kg/m2), normal weight (18.5 to < 25
kg/m2), overweight (25 to < 30 kg/m2), obesity I (30 to < 35 kg/m2), and obesity
II-III (> 35 kg/m2). Diabetes was defined by ICD-9/10 codes in association with
hemoglobin A1c > 6.5% or medication prescriptions. Patients were followed from 180
days post-DAA initiation until 2/14/2019 to assess for development of cirrhosis,
decompensations, hepatocellular carcinoma (HCC), and death. Multivariable Cox
proportional hazards regression models were used to determine the association
between diabetes and/or obesity and outcomes. Result(s): During a mean follow-up of
3 years, 10.1% patients died, 5.0% were newly diagnosed with cirrhosis, 4.7% had a
decompensation and 4.0% developed HCC. Diabetes was associated with an increased
risk of mortality (AHR = 1.25, 95% CI 1.10-1.42), cirrhosis (AHR = 1.31, 95% CI
1.16-1.48), decompensation (AHR = 1.74, 95% CI 1.31-2.31), and HCC (AHR = 1.32, 95%
CI 1.01-1.72) among patients without baseline cirrhosis. Compared to normal-weight
persons, obese persons had a higher risk of cirrhosis, but overweight and obese
persons had lower risk of mortality and HCC. Conclusion(s): In this large DAA-
treated Veterans cohort, pre-DAA diabetes increases mortality and liver-related
events independent of SVR. Continued vigilance is warranted in patients with
diabetes despite SVR. Elevated BMI categories appear to have improved outcomes,
although further studies are needed to understand those associations.Copyright ©
2020, This is a U.S. Government work and not under copyright protection in the US;
foreign copyright protection may apply.
2406&date=2021&title=Digestive+Diseases+and+Sciences&atitle=Nonalcoholic+Fatty+Live
r+Disease+Risk+Factors+Affect+Liver-Related+Outcomes+After+Direct-
Acting+Antiviral+Treatment+for+Hepatitis+C&aulast=Benhammou&pid=%3Cauthor
%3EBenhammou+J.N.%3BMoon+A.M.%3BPisegna+J.R.%3BSu+F.%3BVutien+P.%3BMoylan+C.A.
%3BIoannou+G.N.%3C%2Fauthor%3E%3CAN%3E2005543134%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT
%3E
<40>
Accession Number
2007605303
PMID
Title
A review of non-alcoholic fatty liver disease in non-obese and lean individuals.
Source
Journal of Gastroenterology and Hepatology (Australia). 36(6) (pp 1497-1507),
2021. Date of Publication: June 2021.
Author
Ahadi M.; Molooghi K.; Masoudifar N.; Namdar A.B.; Vossoughinia H.; Farzanehfar
M.
Author NameID
Molooghi, Kasra; ORCID: https://orcid.org/0000-0002-0761-7092
Masoudifar, Negin; ORCID: https://orcid.org/0000-0002-7258-2981
Institution
(Ahadi, Namdar, Vossoughinia, Farzanehfar) Department of Gastroenterology and
Hepatology, Mashhad University of Medical Sciences, Mashhad, Iran, Islamic Republic
of
(Molooghi, Masoudifar) School of Medicine, Mashhad University of Medical
Sciences, Mashhad, Iran, Islamic Republic of
Publisher
Subject Headings
body mass
body weight loss
clinical feature
dietary intake
fatty liver
fructose intake
genetic predisposition
human
intestine flora
*lean body weight
meta analysis (topic)
metabolic disorder
*obesity
pathogenesis
pathophysiology
physical activity
prevalence
prognosis
randomized controlled trial (topic)
review
risk assessment
risk factor
screening test
small intestinal bacterial overgrowth
systematic review (topic)
treatment indication
adipocytokine/ec [Endogenous Compound]
apolipoprotein C3/ec [Endogenous Compound]
cholesterol ester transfer protein/ec [Endogenous Compound]
cytokine/ec [Endogenous Compound]
fat/ec [Endogenous Compound]
phospholipase/ec [Endogenous Compound]
sterol regulatory element binding protein/ec [Endogenous Compound]
unclassified drug
patatin like phospholipase domain containing 3/ec [Endogenous Compound]
sterol regulatory element binding factor/ec [Endogenous Compound]
transmembrane 6 superfamily member 2/ec [Endogenous Compound]
Candidate Terms
patatin like phospholipase domain containing 3 / endogenous compound [drug term]
sterol regulatory element binding factor / endogenous compound [drug term]
transmembrane 6 superfamily member 2 / endogenous compound [drug term]
Drug Index Terms
adipocytokine / endogenous compound; apolipoprotein C3 / endogenous compound;
cholesterol ester transfer protein / endogenous compound; cytokine / endogenous
compound; fat / endogenous compound; insulin / endogenous compound; phospholipase /
endogenous compound; sterol regulatory element binding protein / endogenous
compound; triacylglycerol / endogenous compound; unclassified drug
Other Index Terms
body mass; body weight loss; clinical feature; dietary intake; fatty liver;
fructose intake; genetic predisposition; human; intestine flora; *lean body weight;
meta analysis (topic); metabolic disorder; *nonalcoholic fatty liver / *diagnosis /
*etiology; *obesity; pathogenesis; pathophysiology; physical activity; prevalence;
prognosis; randomized controlled trial (topic); Review; risk assessment; risk
factor; screening test; small intestinal bacterial overgrowth; systematic review
(topic); treatment indication
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of
hepatic disorders. It represents a wide range of chronic liver diseases in patients
with no history of significant alcohol consumption, starting with simple steatosis
and progressing towards non-alcoholic steatohepatitis, cirrhosis, and ultimately
hepatocellular carcinoma. NAFLD is usually associated with type 2 diabetes
mellitus, dyslipidemia, metabolic syndrome, and obesity. This disease has mostly
been studied in obese individuals; however, it has been widely reported and studied
among the lean/non-obese population in recent years. The pathogenesis of NAFLD in
non-obese patients is associated with various genetic predispositions, particularly
a patatin-like phospholipase domain-containing protein 3 G allele polymorphism,
which results in the accumulation of triglyceride in the liver and resistance to
insulin. Additionally, dietary factors such as high fructose consumption seem to
play a substantial role in the pathology of non-obese NAFLD. Although there is not
enough evidence on the treatment of NAFLD in non-obese patients, the standard
approach is to advise altering one's lifestyle in order to diminish visceral
adiposity. Dietary modification, weight loss, and increased physical activity are
highly recommended. We aimed to review and summarize the existing information on
the prevalence, pathogenesis, genetic predispositions, diagnosis, and treatment of
NAFLD in non-obese patients according to the latest literature.Copyright © 2020
Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons
Australia, Ltd
%29&atitle=A+review+of+non-alcoholic+fatty+liver+disease+in+non-
obese+and+lean+individuals&aulast=Ahadi&pid=%3Cauthor%3EAhadi+M.%3BMolooghi+K.
%3BMasoudifar+N.%3BNamdar+A.B.%3BVossoughinia+H.%3BFarzanehfar+M.%3C%2Fauthor%3E
%3CAN%3E2007605303%3C%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<41>
Accession Number
2011029565
PMID
Title
G protein-coupled receptors: Key molecules in metabolic associated fatty liver
disease development.
Source
Nutrition Research. 87 (pp 70-79), 2021. Date of Publication: March 2021.
Author
Lopez-Mendez I.; Mendez-Maldonado K.; Manzo-Francisco L.A.; Juarez-Hernandez E.;
Uribe M.; Barbero-Becerra V.J.
Author NameID
Lopez-Mendez, Ivan; ORCID: https://orcid.org/0000-0002-1614-1022
Mendez-Maldonado, Karla; ORCID: https://orcid.org/0000-0003-3762-0193
Juarez-Hernandez, Eva; ORCID: https://orcid.org/0000-0003-1756-7268
Institution
(Lopez-Mendez) Transplants and Hepatology Unit, Medica Sur Clinic & Foundation,
Mexico City, Mexico
(Mendez-Maldonado) Cellular Physiology Institute, Neurosciences Division &
Physiology and Pharmacology Department, Veterinary and Zootechnics Faculty, UNAM,
Mexico City, Mexico
(Manzo-Francisco, Uribe) Gastrointestinal and Obesity Unit, Medica Sur Clinic &
Foundation, Mexico City, Mexico
(Juarez-Hernandez, Barbero-Becerra) Translational Research Unit, Medica Sur
Clinic & Foundation, Mexico City, Mexico
Publisher
Elsevier Inc.
Subject Headings
disorders of lipid and lipoprotein metabolism
gene
gene expression
gene function
human
immunocompetent cell
intestine flora
lipogenesis
liver cell
*metabolic fatty liver/et [Etiology]
nonhuman
obesity
pathogenesis
review
*G protein coupled receptor/ec [Endogenous Compound]
FFA2 gene
FFA3 gene
FFA4 gene
FFAR1 gene
*GPR gene
gpr120 gene
GPR40 gene
GPR41 gene
GPR43 gene
Candidate Terms
FFA2 gene [other term]
FFAR1 gene [other term]
*GPR gene [other term]
GPR120 gene [other term]
Drug Index Terms
fatty acid / endogenous compound; *G protein coupled receptor / *endogenous
compound
Other Index Terms
disorders of lipid and lipoprotein metabolism; gene; gene expression; gene
function; human; immunocompetent cell; intestine flora; lipogenesis; liver cell;
*metabolic fatty liver / *etiology; nonhuman; obesity; pathogenesis; Review
Abstract
Metabolic associated fatty liver disease (MAFLD) is a range of hepatic disorders
with progression to steatohepatitis with risk of development of fibrosis,
cirrhosis, and hepatocellular carcinoma. MAFLD is strongly related to metabolic
disorders of active fatty acids, which seem to be selective according to their
specific ligand of G protein-coupled receptors (GPRs) located in immune response
cells. An approach to study the pathophysiological mechanisms of MAFLD could be
through the expression of active fatty acids ligands. The expression of GPRs is
associated with obesity, microbiota environment, and dietary characteristics in
patients with MAFLD. More specifically, GPR41, GPR43, GPR20, and GPR120 have been
associated with alteration of lipid metabolism in hepatic and intestinal cells, and
consequently they have a key role in metabolic diseases. We observed that GPR120 is
not expressed in nonoverweight/obese patients, regardless of the presence of MAFLD;
meanwhile the expression of GPR41 is increased in patients with lean MAFLD. GPRs
role in liver disease is intriguing and a field of research opportunity. More
studies are necessary to define the role of active fatty acids in the development
of metabolic diseases.Copyright © 2020 Elsevier Inc.
sid=OVID:embase&id=pmid:33601216&id=doi:10.1016%2Fj.nutres.2020.12.019&issn=0271-
5317&isbn=&volume=87&issue=&spage=70&pages=70-
79&date=2021&title=Nutrition+Research&atitle=G+protein-coupled+receptors
%3A+Key+molecules+in+metabolic+associated+fatty+liver+disease+development&aulast=Lo
pez-Mendez&pid=%3Cauthor%3ELopez-Mendez+I.%3BMendez-Maldonado+K.%3BManzo-
Francisco+L.A.%3BJuarez-Hernandez+E.%3BUribe+M.%3BBarbero-Becerra+V.J.%3C%2Fauthor
<42>
Accession Number
2010828871
PMID
Title
Exome-wide scan identifies significant association of rs4788084 in IL27 promoter
with increase in hepatic fat content among Indians.
Source
Gene. 775 (no pagination), 2021. Article Number: 145431. Date of Publication: 05
Apr 2021.
Author
Chatterjee A.; Basu A.; Das K.; Chowdhury A.; Basu P.
Institution
(Chatterjee, Basu, Basu) National Institute of Biomedical Genomics, Kalyani, West
Bengal, India
(Das, Chowdhury) Institute of Post Graduate Medical Education and Research,
Kolkata, West Bengal, India
Publisher
Elsevier B.V.
Subject Headings
adult
anthropometric parameters
article
disease severity
*exome
*fat content
female
*gene
gene function
gene linkage disequilibrium
gene locus
gene mapping
*genetic association
genetic risk
*genetic variability
HOMA index
human
*Indian
liver biopsy
liver level
male
molecular genetics
obesity
priority journal
*promoter region
proton nuclear magnetic resonance
quantitative trait locus
single nucleotide polymorphism
high density lipoprotein/ec [Endogenous Compound]
low density lipoprotein/ec [Endogenous Compound]
very low density lipoprotein/ec [Endogenous Compound]
fam161a gene
*IL27 gene
pnpla3 gene
SAMM50 gene
Candidate Terms
FAM161A gene [other term]
*IL27 gene [other term]
PNPLA3 gene [other term]
SAMM50 gene [other term]
Drug Index Terms
endogenous compound; high density lipoprotein / endogenous compound; low density
lipoprotein / endogenous compound; triacylglycerol / endogenous compound; very low
density lipoprotein / endogenous compound
Other Index Terms
adult; anthropometric parameters; Article; cholesterol blood level; disease
severity; *exome; *fat content; female; *gene; gene function; gene linkage
disequilibrium; gene locus; gene mapping; *genetic association; genetic risk;
*genetic variability; HOMA index; human; *Indian; liver biopsy; liver level; major
clinical study; male; molecular genetics; nonalcoholic steatohepatitis; obesity;
priority journal; *promoter region; proton nuclear magnetic resonance; quantitative
trait locus; single nucleotide polymorphism; triacylglycerol blood level
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is a global epidemic that
often progresses to liver cirrhosis and hepatocellular carcinoma. In contrast to
most world populations where NAFLD is mostly prevalent among obese, NAFLD among
Indians and generally among South and South-East Asians is unique and highly
prevalent among individuals who are lean. Genetics of NAFLD in Indian populations
is understudied. In this study, we have used an exome-wide approach to identify
genetic determinants of hepatic fat content (HFC) in India. Method(s): HFC was
measured in 244 participants using Proton magnetic resonance spectroscopy (H1-MRS).
Quantitative trait loci (QTL) mapping was done exome-wide, to identify SNPs
associated with HFC. The effects of the interaction between adiposity and QTLs on
HFC were studied using a regression model. Association of the significant loci with
disease severity was studied in 146 NAFLD patients among 244 participants, who
underwent liver biopsy. Result(s): Our study identified 4 significantly associated
SNPs (rs738409 and rs2281135 (PNPLA3), rs3761472 (SAMM50), rs17513722 (FAM161A) and
rs4788084), with HFC after adjusting for the effects of covariates (p-value <
0.0005). rs738409, rs2281135 (PNPLA3), and rs3761472 (SAMM50) were associated with
hepatocyte ballooning, lobular and portal inflammation and non-alcoholic
steatohepatitis (NASH) (p-value < 0.05). rs4788048 is an eQTL for IL27 and SULT1A2
genes, both of which are highly expressed in healthy livers and are likely to be
involved in NAFLD pathogenesis. Conclusion(s): Our study identified the novel
association of rs4788084 with HFC, which regulates the expression of IL-27, an
immune regulatory gene. We further showed that adiposity affected the HFC,
irrespective of the genetic predisposition.Copyright © 2021 Elsevier B.V.
sid=OVID:embase&id=pmid:33444683&id=doi:10.1016%2Fj.gene.2021.145431&issn=0378-
1119&isbn=&volume=775&issue=&spage=145431&pages=&date=2021&title=Gene&atitle=Exome-
wide+scan+identifies+significant+association+of+rs4788084+in+IL27+promoter+with+inc
rease+in+hepatic+fat+content+among+Indians&aulast=Chatterjee&pid=%3Cauthor
%3EChatterjee+A.%3BBasu+A.%3BDas+K.%3BChowdhury+A.%3BBasu+P.%3C%2Fauthor%3E%3CAN
<43>
Accession Number
636385922
Title
Non-alcoholic steatohepatitis-induced hepatocellular carcinoma in obese and non-
obese mice.
Source
Hepatology. Conference: 72nd Annual Meeting of the American Association for the
Study of Liver Diseases, AASLD 2021. Virtual. 74(SUPPL 1) (pp 705A), 2021. Date of
Author
Vlock E.; Fisher K.; Farazi P.
Institution
(Vlock, Farazi) Epidemiology, University of Nebraska Medical Center
(Fisher) Pathology and Microbiology, University of Nebraska Medical Center
Publisher
Subject Headings
adult
animal experiment
animal model
animal tissue
C57BL/6N mouse
cancer growth
cancer size
cancer survival
cholesterol diet
conference abstract
controlled study
fatty acid analysis
fatty acid level
female
glucose blood level
glucose intolerance
insulin resistance
lipid storage
liver biopsy
liver cirrhosis
male
mouse
mouse model
mouse mutant
nonhuman
*obesity
penetrance
phenotype
tumor growth
unhealthy diet
choline
fructose
liver enzyme
polyunsaturated fatty acid
Drug Index Terms
choline; fructose; liver enzyme; polyunsaturated fatty acid
Other Index Terms
adult; animal experiment; animal model; animal tissue; C57BL/6N mouse; cancer
growth; cancer size; cancer survival; cholesterol blood level; cholesterol diet;
conference abstract; controlled study; fatty acid analysis; fatty acid level;
female; glucose blood level; glucose intolerance; insulin resistance; lipid
storage; liver biopsy; *liver cell carcinoma; liver cirrhosis; male; mouse; mouse
model; mouse mutant; *nonalcoholic steatohepatitis; nonhuman; *obesity; penetrance;
phenotype; tumor growth; unhealthy diet
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver
disease in Western countries. It can develop in the context of obesity and diabetes
as well as in lean individuals in the absence of metabolic syndrome. Lean NAFLD has
a prevalence of 7 percent in the U.S. and 25-30 percent in some Asian countries.
NAFLD starts with excess liver fat accumulation (NAFL) that can progress to
nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately hepatocellular
carcinoma (HCC). To date, little is known regarding the pathogenesis of lean NASH-
HCC and how it compares with obese NASH-HCC. To address this gap, we generated
mouse models of lean and obese NASH-HCC using a high trans-fat/fructose/cholesterol
(HFFC) diet that is choline deficient or choline supplemented, respectively.
Method(s): C57BL/6N mice were fed a HFFC diet (in one group the diet was choline
deficient and in the other group the diet was choline supplemented) starting at 4
weeks of age for 60 weeks. Plasma glucose tolerance, insulin resistance, lipid and
liver enzyme profiles of these mice were assessed at different timepoints. A liver
biopsy was conducted at 20 weeks to determine the liver phenotype at that time and
compare to the phenotype at the endpoint. The plasma and tumor fatty acid profile
of these mice was also investigated. Result(s): Glucose intolerance and insulin
resistance were more pronounced in obese mice, who also showed higher levels of
plasma cholesterol and trigylcerides, and higher penetrance of NASH compared to
lean mice. Male obese and lean mice developed HCC with similar penetrance (53.3%
and 53.8%, respectively), however lean mice showed faster tumor progression as
supported by the larger tumor size and lower HCC-free survival. Female obese mice
developed HCC with 50% penetrance, whereas none of the female lean mice developed
HCC. Both groups of mice showed a reduction in plasma polyunsaturated fatty acids
(PUFAs), however, the levels were higher towards the endpoint in obese mice
compared to lean mice. Conclusion(s): In male mice, unhealthy diet composition
appears to drive progression to NASHHCC rather than the organismal effects of
obesity, whereas in female mice obesity promotes tumor progression in the context
of an unhealthy diet. PUFA levels may increase over time in obese mice due to
systemic inflammation and act as suppressors of tumor progression, thus delaying
HCC progression in obese mice compared to lean mice.
3350&isbn=&volume=74&issue=SUPPL+1&spage=705A&pages=705A&date=2021&title=Hepatology
&atitle=Non-alcoholic+steatohepatitis-
induced+hepatocellular+carcinoma+in+obese+and+non-obese+mice&aulast=Vlock&pid=
%3Cauthor%3EVlock+E.%3BFisher+K.%3BFarazi+P.%3C%2Fauthor%3E%3CAN%3E636385922%3C
<44>
Accession Number
636385705
Title
Changing clinicopathological profile and clinical outcomes in a real-world large
cohort of patients with nonalcoholic fatty liver disease (nafld) from south-asia -
Interim results of the icon-d (indian consortium on nafld) study.
Source
Study of Liver Diseases, AASLD 2021. Virtual. 74(SUPPL 1) (pp 998A), 2021. Date of
Author
Duseja A.K.; Singh S.P.; Mehta M.; Shalimar; Venkataraman J.; Mehta V.; Devadas
K.; Kar S.; Goyal O.; Nagral A.; Saigal S.; Nijhawan S.; Praharaj D.; Shukla A.;
Sharma B.; Narayanasamy K.; Da P.K.; Rao P.N.; Arora A.; Mehta R.M.; Asati P.;
Ranjan P.; Koshy A.; Alam S.; Mukewar S.; Mohan Prasad V.G.; Rastogi M.; Sanyal
A.J.
Institution
(Duseja, Mehta) Department of Hepatology, Postgraduate Institute of Medical
Education & Research (PGIMER), Chandigarh, India
(Singh) Department of Gastroenterology, S.C.B Medical College Hospital, Cuttack,
India
(Shalimar) Department of Gastroenterology, All India Institute of Medical
Sciences, New Delhi, India
(Venkataraman) Department of Hepatology, Sri Ramachandra Institute of Higher
Education & Research, Chennai, India
(Mehta) Department of Gastroenterology, Dayanand Medical College and Hospital,
Ludhiana, India
(Devadas) Department of Gastroenterology, Government Medical College, Trivandrum,
India
(Kar) Gastro Liver Care, Cuttack, India
(Goyal) Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
(Nagral) Jaslok Hospital Mumbai, India
(Saigal) Institute of Liver Transplantation and Regenerative Medicine, Medanta,
the Medicity, Gurugram, India
(Nijhawan) Department of Gastroenterology, SMS Medical College and Hospital,
Jaipur, India
(Praharaj) Department of Gastroenterology and Hepatology, Kalinga Institute of
Medical Sciences, Bhubaneshwar, India
(Shukla) Department of Gastroenterology, Seth Gsmc & Kem Hospital, Mumbai, India
(Sharma) Department of Gastroenterology, Indira Gandhi Medical College &
Hospital, Shimla, India
(Narayanasamy) Department of Hepatology, Madras Medical College, Chennai, India
(Da) Centre of Liver Sciences, Aig Hospitals, Hyderabad, India
(Rao) Hepatology, Asian Institute of Gastroenterology
(Arora, Ranjan) Department of Gastroenterology and Hepatology, Sir Gangaram
Hospital, New Delhi, India
(Mehta) Department of Gastroenterology, Surat Institute of Medical Sciences
(SIDS), Surat, Gujarat, India
(Asati) NSC Bose Medical College and Hospital, Jabalpur, India
(Koshy) Department of Hepatology, VPS Lakeshore, Kochi, India
(Alam) Institute of Liver and Biliary Sciences, Department of Pediatric
Hepatology, New Delhi, India
(Mukewar, Mukewar) MIDAS Hospital, Nagpur, India
(Mohan Prasad) Institute of Gastroenterology, Vgm Hospital, Coimbatore, India
(Rastogi) Department of Hepatology, Gastroenterology and Liver Transplant, Fortis
Hospital, Noida, India
(Sanyal) Department of Internal Medicine, Division of Gastroenterology, Virginia
Commonwealth University
Publisher
Subject Headings
abdominal obesity
adult
anthropometry
ascites
aspartate aminotransferase to platelet ratio index
body mass
*clinical outcome
cohort analysis
conference abstract
elastograph
fibrosis
follow up
fracture
heart infarction
*histology
histopathology
human
human tissue
*India
jaundice
liver cirrhosis
liver dysfunction
male
middle aged
multicenter study
obesity
*outcome assessment
risk assessment
risk factor
Other Index Terms
abdominal obesity; adult; anthropometry; ascites; aspartate aminotransferase to
platelet ratio index; body mass; *clinical outcome; cohort analysis; conference
abstract; elastograph; fibrosis; follow up; fracture; heart infarction; *histology;
histopathology; human; human tissue; *India; jaundice; liver cirrhosis; liver
dysfunction; major clinical study; male; metabolic syndrome X; middle aged;
multicenter study; *nonalcoholic steatohepatitis; obesity; *outcome assessment;
risk assessment; risk factor
Abstract
Background: Previous data from south-Asia and India had shown that patients with
NAFLD have mild liver disease severity. There is no data regarding long-term
clinical outcome in patients with NAFLD from south-Asia. Objective of the study was
to analyze the clinicopathological profile and long-term clinical outcome of NAFLD
in a large reallife Indian cohort. Method(s): In an on-going study [Indian
Consortium on NAFLD (ICON-D)], interim data captured across 23 centers in India
over 18 months was analyzed. In addition to metabolic risk factors, severity of
NAFLD was assessed by non-invasive scores/elastography and histology.
Hepatic/extra-hepatic events were recorded on follow up in patients with different
severity of liver disease. Result(s): Of 4313 patients with NAFLD (Mean age 45+/-
12.2 years, males 52%), anthropometry/metabolic syndrome data in 3553 (82.3%)
patients (mean BMI 27.6 +/- 5.7 Kg/m2) revealed that 378 (10.6%) were lean, 575
(16.2%) overweight and 2584 (72.7%) were obese. Metabolic syndrome was present in
1518 (42.7 %); at least one metabolic risk factor in 3292 (92.6%); commonest being
central obesity [2981 (83.9%)]. As per AST to platelet ratio index (APRI) [n=3196
(74%)], 682 (21.3%) patients had significant fibrosis (APRI>1.5); as per Fibrosis-4
(FIB-4) [n=3554 (82.4%)], 676 (19%) patients had advanced fibrosis (FIB-4 > 3.25)
and as per NFS [n= 1924 (44.6%)], 397 (20.6%) had a score >=0.676 suggestive of
significant fibrosis. Fibroscan data [n=2475, (57.3%)] revealed significant
fibrosis (LSM >= 8kPa) in 715 (29 %) and cirrhosis (LSM >= 13 kPa) in 246 (10%). On
histology [n=267 (6.2%)], 57 (21.3%) had no-NASH, 89 (33.3%) borderline NASH and
131 (49 %) definite NASH; 92 (34.4%) patients had >=F2 fibrosis, 41 (15.4%) had
advanced fibrosis (F3-F4) and 22 (8.2%) patients had evidence of cirrhosis. On a
mean follow up 43.5 months, hepatic and extra-hepatic events recorded in 1353
(31.3%) patients showed that patients with compensated cirrhosis [LSM>= 13 kPa,
n=71 (5.2%)] had more hepatic events [26 (36.7%)] (jaundice-3, UGI bleed- 3, HCC-2,
HE - 8 and ascites-10) and extra-hepatic events [8 (11.3%)] (CKD-5, myocardial
infarction -2, and bone fracture -1) in comparison to those without cirrhosis
(p<0.0001). Conclusion(s): In a large real-life cohort, a significant number of
patients with NAFLD in India have NASH and significant/advanced fibrosis or
cirrhosis at presentation. Our results suggest a changing clinico-pathological
profile of NAFLD in south-Asia. Clinical outcome data from our study suggest that
both hepatic and extra-hepatic events on follow up are observed more commonly in
patients with NASH related compensated cirrhosis.
3350&isbn=&volume=74&issue=SUPPL+1&spage=998A&pages=998A&date=2021&title=Hepatology
&atitle=Changing+clinicopathological+profile+and+clinical+outcomes+in+a+real-
world+large+cohort+of+patients+with+nonalcoholic+fatty+liver+disease+%28nafld
%29+from+south-asia+-+Interim+results+of+the+icon-d+%28indian+consortium+on+nafld
%29+study&aulast=Duseja&pid=%3Cauthor%3EDuseja+A.K.%3BSingh+S.P.%3BMehta+M.
%3BShalimar%3BVenkataraman+J.%3BMehta+V.%3BDevadas+K.%3BKar+S.%3BGoyal+O.
%3BNagral+A.%3BSaigal+S.%3BNijhawan+S.%3BPraharaj+D.%3BShukla+A.%3BSharma+B.
%3BNarayanasamy+K.%3BDa+P.K.%3BRao+P.N.%3BArora+A.%3BMehta+R.M.%3BAsati+P.
%3BRanjan+P.%3BKoshy+A.%3BAlam+S.%3BMukewar+S.%3BMohan+Prasad+V.G.%3BRastogi+M.
%3BSanyal+A.J.%3C%2Fauthor%3E%3CAN%3E636385705%3C%2FAN%3E%3CDT
<45>
Accession Number
635444007
Title
Steatosis: A lubricant for the development and progression of alcoholic liver
disease.
Source
Alcoholism: Clinical and Experimental Research. Conference: 44th Annual Meeting
of the Research Society on Alcoholism, RSA 2021. Virtual. 45(SUPPL 1) (pp 28A),
2021. Date of Publication: June 2021.
Author
Mahli A.; Sommer J.; Koch A.; Hellerbrand C.
Institution
(Mahli, Sommer, Koch, Hellerbrand) Friedrich-Alexander University Erlangen-
Nurnberg, Institute of Biochemistry, Erlangen 91054, Germany
Publisher
Blackwell Publishing Ltd
Subject Headings
adult
alcohol consumption
*alcohol liver disease
animal cell
animal experiment
animal model
*cancer growth
cancer prognosis
cell proliferation
conference abstract
controlled study
culture medium
disease simulation
*drug potentiation
drug toxicity
enzyme activity
fibrosis
human
inflammation
lipid diet
lipid storage
liver cancer
liver cell damage
liver toxicity
male
mouse
nonhuman
obese patient
obesity
protein expression
signal transduction
*steatosis
synergistic effect
alcohol
cytochrome P450 2E1
drinking water
endogenous compound
fatty acid
*lubricating agent
stress activated protein kinase
Drug Index Terms
alcohol; cytochrome P450 2E1; drinking water; endogenous compound; fatty acid;
*lubricating agent; stress activated protein kinase
Other Index Terms
adult; alcohol consumption; *alcohol liver disease; animal cell; animal
experiment; animal model; *cancer growth; cancer prognosis; cell proliferation;
conference abstract; controlled study; culture medium; disease simulation; *drug
potentiation; drug toxicity; enzyme activity; fibrosis; human; inflammation; lipid
diet; lipid storage; liver cancer; liver cell damage; liver toxicity; male; mouse;
nonhuman; obese patient; obesity; protein expression; signal transduction;
*steatosis; synergistic effect
Abstract
The spectrum of alcoholic liver disease (ALD) is broad. However, only a fraction
of drinkers develop significant hepatic inflammation, and even less progress to
hepatic fibrosis/cirrhosis or hepatocellular cancer (HCC). Next to ALD, obesity
induced hepatic steatosis emerges as one of the major reasons for (non-alcoholic)
fatty liver disease worldwide. Clinical studies suggest a causative link between
obesity and ALD-progression. However, it is incompletely understood how alcohol and
obesity interact and whether the combined effects are additive or synergistic. We
aimed to develop experimental models to address this question and to unravel
molecular mechanisms of combined effects of alcohol and steatosis. Once, we used an
in vitro model of hepatocellular lipid accumulation in primary human hepatocytes
(PHH) in combination with alcohol treatment. This combination significantly
increased steatosis, hepatocellular injury and proinflammatory gene expression
compared with cells with only steatosis or alcohol stimulation, respectively. These
combined effects were accompanied by increased CYP2E1 expression and activity and
induction of the JNK-pathway. Conversely, CYP2E1 or JNK-inhibition almost
completely blunted the combined alcohol/steatosis effects. Furthermore, mice were
fed with a steatosis inducing high-fat diet (HFD), received alcohol in the drinking
water or a combination of both. Control mice were fed with standard chow. The
combination of HFD and alcohol caused significantly increased steatosis,
inflammation and fibrosis, together with markedly induced CYP2E1 and JNK-
activation, compared with only moderate effects of alcohol or HFD alone. Moreover,
we found that free fatty acids in culture medium of hepatocellular cancer (HCC)
cells, a model simulating high circulating levels of fatty acids in obese
individuals, induced steatosis in the HCC cells, and additional treatment with
alcohol induced the proliferation, migratory activity and JNK-activity of the
steatotic HCC cells, while the same alcohol dose alone had no effects on control
HCC cells. In conclusion, alcohol exhibits synergistic pathological effects with
(dietary) induced steatosis already at moderate doses, indicating significant
differences in the dose threshold for hepatotoxic effects in lean and obese
subjects. Moreover, our data indicate a synergistic effect of alcohol and steatosis
on HCC-progression. CYP2E1 and JNK-activation appear as critical mediators of these
combined effects, which could lead to new prognostic markers and therapeutic
targets for ALD particularly in obese individuals.
sid=OVID:embase&id=pmid:&id=doi:10.1111%2Facer.14617&issn=1530-
0277&isbn=&volume=45&issue=SUPPL+1&spage=28A&pages=28A&date=2021&title=Alcoholism
%3A+Clinical+and+Experimental+Research&atitle=Steatosis
%3A+A+lubricant+for+the+development+and+progression+of+alcoholic+liver+disease&aula
st=Mahli&pid=%3Cauthor%3EMahli+A.%3BSommer+J.%3BKoch+A.%3BHellerbrand+C.%3C
%2Fauthor%3E%3CAN%3E635444007%3C%2FAN%3E%3CDT%3EConference+Abstract%3C%2FDT%3E
<46>
Accession Number
634543227
Title
Inhibition of the IL-1R1 pathway in hepatocytes reduces tumor growth in a mouse
model of NAFLD-associated HCC.
Source
Zeitschrift fur Gastroenterologie. Conference: 37. Jahrestagung der Deutschen
Arbeitsgemeinschaft zum Studium der Leber. Munster Germany. 59(1) (pp e38-e39),
2021. Date of Publication: January 2021.
Author
Gehrke N.; Straub B.K.; Worns M.A.; Galle P.R.; Schattenberg J.M.
Institution
(Gehrke, Straub, Worns, Galle, Schattenberg) University Medical Center Mainz, I.
Department of Medicine, Mainz, Germany
Publisher
Georg Thieme Verlag
Subject Headings
adult
aminotransferase blood level
animal cell
animal experiment
animal model
animal tissue
cancer size
carbohydrate diet
CD4+ T lymphocyte
conference abstract
feeding
fibrosis
gene expression
genotype
hepatomegaly
*histology
histopathology
HOMA index
hyperglycemia
hyperlipidemia
incidence
inflammation
insulin sensitivity
knockout gene
left lateral liver lobe
liver injury
*liver tumor
male
mouse
*mouse model
nonhuman
obesity
phenotype
protein expression
protein function
*signal transduction
transgenic mouse
*tumor growth
tumor volume
wild type mouse
CXCL1 chemokine
diethylnitrosamine
endogenous compound
interleukin 1
*interleukin 1 receptor type I
monocyte chemotactic protein 1
Drug Index Terms
CXCL1 chemokine; diethylnitrosamine; endogenous compound; interleukin 1;
*interleukin 1 receptor type I; monocyte chemotactic protein 1
Other Index Terms
adult; aminotransferase blood level; animal cell; animal experiment; animal
model; animal tissue; cancer size; carbohydrate diet; CD4+ T lymphocyte; conference
abstract; feeding; fibrosis; gene expression; genotype; hepatomegaly; *histology;
histopathology; HOMA index; hyperglycemia; hyperlipidemia; incidence; inflammation;
insulin sensitivity; knockout gene; left lateral liver lobe; liver carcinogenesis;
liver injury; *liver tumor; male; mouse; *mouse model; *nonalcoholic fatty liver;
nonhuman; obesity; phenotype; protein expression; protein function; *signal
transduction; transgenic mouse; *tumor growth; tumor volume; wild type mouse
Abstract
Question Non-alcoholic fatty liver disease (NAFLD) is a relevant risk factor for
developing hepatocellular carcinoma (HCC) even in the absence of advanced fibrosis
or cirrhosis; however, little is known about the specific molecular mechanisms
involved. Given the critical role of interleukin (IL)-1 signaling in inflammation
and metabolism, we used hepatocyte-specific IL-1 receptor type 1 (IL-1R1) knockout
(Il1r1) mice to examine the contribution of this pathway in NAFLD-associated
hepatocarcinogenesis. Methods Diethylnitrosamine (DEN, 25 mg/kg) was given i.p. to
2-week-old, male Il1r1 mice and wild-type (WT) littermates. From 6 weeks of age the
mice were fed either a high-fat, high-carbohydrate diet (HFD, n=8/genotype) or a
control diet (CD, n=4/genotype) until sacrifice at 24 weeks of age. Results In
contrast to the DEN/CD groups with a lean phenotype, all mice treated with DEN/HFD
displayed significant obesity, hyperlipidemia, and hyperglycemia; however Il1r1
mice were less susceptible to elevations of fasting glucose and HOMA-IR levels
compared to WT mice. Both genotypes were similar prone to develop HFD-induced liver
enlargement, elevated serum transaminases, and NAFL-histology with macrovesicular
steatosis, but without significant inflammation or fibrosis. Additionally, adding
HFD to DEN led to a significant increase in macroscopically visible dysplastic
lesions in liver tissue compared to the CD. Despite heterogeneity, the average
number and volume of tumors formed in Il1r1 livers were lower than those for WT
mice, two of which developed 10mm tumor nodules. Also histopathological examination
of the left lateral liver lobe revealed a 2.7-fold increase in dysplastic foci >1mm
in WT compared to transgenic mice. While both DEN/HFD groups exhibited a comparable
increase in circulating MCP-1 levels and relative number of GR1 F4/80 intrahepatic
cells in parallel to a slight decrease of CD4 T cells, increases in serum CXCL-1
were less pronounced in Il1r1 mice compared to WT littermates. Conclusions HFD-
feeding to DEN-injected mice strongly enhances liver tumor development with an
incidence rate of 100% at already 24 weeks of age. There is early evidence that
inhibition of the IL-1R1 pathway in hepatocytes leads to reduced tumor growth under
these conditions. It remains to be determined whether improved insulin sensitivity
and/or inflammatory processes in Il1r1 mice are critical for reduced tumor burden.
sid=OVID:embase&id=pmid:&id=doi:10.1055%2Fs-0040-1722049&issn=1439-
7803&isbn=&volume=59&issue=1&spage=e38&pages=e38-
e39&date=2021&title=Zeitschrift+fur+Gastroenterologie&atitle=Inhibition+of+the+IL-
1R1+pathway+in+hepatocytes+reduces+tumor+growth+in+a+mouse+model+of+NAFLD-
associated+HCC&aulast=Gehrke&pid=%3Cauthor%3EGehrke+N.%3BStraub+B.K.%3BWorns+M.A.
%3BGalle+P.R.%3BSchattenberg+J.M.%3C%2Fauthor%3E%3CAN%3E634543227%3C%2FAN%3E%3CDT
<47>
Accession Number
2005869041
Title
PGI3 LEAN AND OBESE PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS (NASH) / NON-
ALCOHOLIC FATTY LIVER DISEASE (NALFD); COMPARISONS OF POPULATIONS AND DISEASE
PROGRESSION.
Source
Value in Health. Conference: ISPOR 2020. Orlando United States. 23(Supplement 1)
(pp S143), 2020. Date of Publication: May 2020.
Author
Lai M.; Frick A.; Haubrich R.; Koch B.; Milligan S.; Natha M.; Radtchenko J.;
Younossi Z.; Afdhal N.
Institution
(Lai, Afdhal) Beth Israel Deaconess Medical Center, Boston, MA, United States
(Frick, Milligan, Radtchenko) Trio Health Analytics, La Jolla, CA, United States
(Haubrich, Koch, Natha) Gilead Sciences, Inc., Foster City, CA, United States
(Younossi) Center for Liver Diseases, Department of Medicine, Inova Fairfax
Hospital, Falls Church, VA, United States
Publisher
Elsevier Ltd
Subject Headings
adult
advanced cancer
alcohol abuse
body mass
*cancer patient
cohort analysis
comorbidity
conference abstract
controlled study
coronavirus disease 2019
diabetes mellitus
female
fibrosis
follow up
gender
human
hyperlipidemia
hypertension
ICD-10
incidence
liver cirrhosis
liver graft
male
*obese patient
*obesity
propensity score
race
endogenous compound
glucagon like peptide 1 receptor agonist
hydroxymethylglutaryl coenzyme A reductase inhibitor
*prostaglandin I3
protein c jun
sodium glucose cotransporter 2 inhibitor
Drug Index Terms
endogenous compound; glucagon like peptide 1 receptor agonist;
hydroxymethylglutaryl coenzyme A reductase inhibitor; *prostaglandin I3; protein c
jun; sodium glucose cotransporter 2 inhibitor
Other Index Terms
adult; advanced cancer; alcohol abuse; body mass; *cancer patient; cohort
analysis; comorbidity; conference abstract; controlled study; coronavirus disease
2019; diabetes mellitus; female; fibrosis; follow up; gender; human;
hyperlipidemia; hypertension; ICD-10; incidence; liver cell carcinoma; liver
cirrhosis; liver graft; major clinical study; male; *nonalcoholic steatohepatitis;
*obese patient; *obesity; propensity score; race
Abstract
Objectives: To assess differences in characteristics and disease progression in
lean (BMI <25) compared to obese (BMI >30) patients with NASH/NAFLD. Method(s): US
EMR data were limited to adults with NASH/NAFLD (ICD10 K76, 75.81) with BMI <25 or
>=30 but without viral hepatitis, advanced liver disease or evidence of alcohol
abuse. Baseline date was the first calculable FIB4 between July 2015 - Jun 2017
with >1 year history and >2 years follow-up or death. Definition of advanced liver
disease (ALD): cirrhosis (compensated/decompensated), hepatocellular carcinoma,
liver transplant. Observed incidence rates were cases per 1000 person-years to
event, death, or end of observation (Jun 2019); differences between groups assessed
by log-rank. Propensity score matching (PSM) adjusted for age, race, gender,
baseline FIB4, comorbidities, and use of GLP-1 receptor agonists, SGLT-2 inhibitors
and statins. Result(s): Of 6806 patients, 1232 (18%) were lean and 5574 (82%) obese
with median follow-up of 2.6 and 2.9 years respectively. Obese had lower
proportions of age >=75 (5% vs 11%, p<0.001), females (60% vs 70%, p<0.001), and
FIB4 >=2.67 (6% vs. 12%, p<0.001) and higher proportions of diabetes (41% vs. 20%,
p<0.001), hypertension (52% vs 37%, p<0.001), hyperlipidemia (65% vs 40%, p<0.001),
and statin use (43% vs 28%, p<0.001). PSM yielded 1184 pairs. Incidence [CI] of ALD
was significantly higher in lean vs obese in full (115.37 [103.02-128.8] v. 65.94
[61.86-70.21], p<0.001) and matched cohort comparisons (115.95 [103.32-129.7] v.
71.96 [62.76-82.12], p<0.001). Incidence rates increased with increasing FIB4 score
and significant differences between lean and obese group rates were limited to
patients with less severe fibrosis (FIB4 <2.67). Conclusion(s): Lean NASH/NAFLD
patients were more likely to develop ALD compared to obese. However, in patients
with severe fibrosis (FIB4 >=2.67), which had the highest incidence rates of ALD,
rates were not statistically different between lean and obese groups.Copyright ©
2020
sid=OVID:embase&id=pmid:&id=doi:10.1016%2Fj.jval.2020.04.363&issn=1098-
3015&isbn=&volume=23&issue=Supplement+1&spage=S143&pages=S143&date=2020&title=Value
+in+Health&atitle=PGI3+LEAN+AND+OBESE+PATIENTS+WITH+NON-ALCOHOLIC+STEATOHEPATITIS+
%28NASH%29+%2F+NON-ALCOHOLIC+FATTY+LIVER+DISEASE+%28NALFD
%29%3B+COMPARISONS+OF+POPULATIONS+AND+DISEASE+PROGRESSION&aulast=Lai&pid=%3Cauthor
%3ELai+M.%3BFrick+A.%3BHaubrich+R.%3BKoch+B.%3BMilligan+S.%3BNatha+M.
%3BRadtchenko+J.%3BYounossi+Z.%3BAfdhal+N.%3C%2Fauthor%3E%3CAN%3E2005869041%3C%2FAN
%3E%3CDT%3EConference+Abstract%3C%2FDT%3E
<48>
Accession Number
632578595
Title
Reduction of polyunsaturated fatty acids with tumor progression in a lean non-
alcoholic steatohepatitis- associated hepatocellular carcinoma mouse model.
Source
Journal of Cancer. 11(19) (pp 5536-5546), 2020. Date of Publication: 2020.
Author
Vlock E.M.; Karanjit S.; Talmon G.; Farazi P.A.
Institution
(Vlock, Karanjit, Farazi) Department of Epidemiology, College of Public Health,
(Vlock, Farazi) Nebraska Center for the Prevention of Obesity Diseases Through
Dietary Molecules, College of Education and Human Sciences, University of Nebraska
Lincoln, Lincoln, NE, United States
(Talmon) Department of Pathology and Microbiology, College of Medicine,
Publisher
Ivyspring International Publisher (E-mail: [email protected])
Subject Headings
animal experiment
animal model
animal tissue
article
blood analysis
C57BL/6N mouse
cholesterol diet
comparative study
controlled study
disease association
fatty acid blood level
female
hepatomegaly
high fat/high sucrose diet
lipid metabolism
lipogenesis
low fat diet
molecular biology
mouse
nonhuman
splenomegaly
tissue level
treatment duration
*tumor growth
adenosine triphosphate citrate synthase/ec [Endogenous Compound]
arachidic acid/ec [Endogenous Compound]
beta actin/ec [Endogenous Compound]
cystathionine beta synthase/ec [Endogenous Compound]
docosahexaenoic acid/ec [Endogenous Compound]
fatty acid synthase/ec [Endogenous Compound]
homocysteine/ec [Endogenous Compound]
icosapentaenoic acid/ec [Endogenous Compound]
linoleic acid/ec [Endogenous Compound]
linolenic acid/ec [Endogenous Compound]
messenger RNA/ec [Endogenous Compound]
methylenetetrahydrofolate dehydrogenase/ec [Endogenous Compound]
omega 3 fatty acid/ec [Endogenous Compound]
omega 6 fatty acid/ec [Endogenous Compound]
palmitoleic acid/ec [Endogenous Compound]
peroxisome proliferator activated receptor alpha/ec [Endogenous Compound]
*polyunsaturated fatty acid/ec [Endogenous Compound]
sterol regulatory element binding protein 1/ec [Endogenous Compound]
sucrose
tetrahydrofolic acid/ec [Endogenous Compound]
unclassified drug
SREBP cleavage activating protein/ec [Endogenous Compound]
Candidate Terms
srebp cleavage activating protein / endogenous compound [drug term]
Drug Index Terms
adenosine triphosphate citrate synthase / endogenous compound; alanine
aminotransferase / endogenous compound; arachidic acid / endogenous compound;
aspartate aminotransferase / endogenous compound; beta actin / endogenous compound;
cholesterol / endogenous compound; cystathionine beta synthase / endogenous
compound; docosahexaenoic acid / endogenous compound; fatty acid synthase /
endogenous compound; homocysteine / endogenous compound; icosapentaenoic acid /
endogenous compound; linoleic acid / endogenous compound; linolenic acid /
endogenous compound; messenger RNA / endogenous compound; methylenetetrahydrofolate
dehydrogenase / endogenous compound; omega 3 fatty acid / endogenous compound;
omega 6 fatty acid / endogenous compound; palmitoleic acid / endogenous compound;
peroxisome proliferator activated receptor alpha / endogenous compound;
*polyunsaturated fatty acid / *endogenous compound; sterol regulatory element
binding protein 1 / endogenous compound; sucrose; tetrahydrofolic acid / endogenous
compound; triacylglycerol / endogenous compound; unclassified drug
Other Index Terms
animal experiment; animal model; animal tissue; Article; blood analysis; C57BL/6N
mouse; cholesterol diet; comparative study; controlled study; disease association;
disease exacerbation; fatty acid blood level; female; hepatomegaly; high fat/high
sucrose diet; lipid metabolism; lipogenesis; *liver cell carcinoma / *etiology; low
fat diet; molecular biology; mouse; *nonalcoholic steatohepatitis; nonhuman;
splenomegaly; tissue level; treatment duration; *tumor growth
Abstract
Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common
liver disease in Western countries. While obesity and diabetes are the hallmarks of
NAFLD, it also develops in lean individuals in the absence of metabolic syndrome,
with a prevalence of 7 percent in the U.S. and 25-30 percent in some Asian
countries. NAFLD represents the spectrum of liver disease, starting with excess
liver fat accumulation (NAFL) that can progress to nonalcoholic steatohepatitis
(NASH), cirrhosis and ultimately hepatocellular carcinoma (HCC). To date, the
pathogenesis of lean NASH-HCC is poorly understood and a mouse model is lacking. We
aimed to develop a mouse model of lean NASH-HCC using a choline deficient and high
trans-fat/sucrose/cholesterol diet to enable better understanding of its molecular
pathogenesis. Method(s): C57BL/6N mice were fed this diet starting at 4 weeks of
age for 52 weeks and were compared to mice fed an isocaloric low fat control diet
for the same duration. C57BL/6N mice were chosen instead of the C57BL/6J mice due
to the high susceptibility of C57BL/6J mice to diet-induced obesity. The plasma and
tumor fatty acid profile of these mice was also investigated. Result(s): Nearly 61%
of the mice developed lean NASH-HCC. These mice showed reduction of plasma
polyunsaturated fatty acids (PUFAs) (linolenic acids (alpha and gamma, omega-3 and
omega-6, respectively), eicosapentanoic acid (omega-3), docosahexanoic acid (omega-
3), and linoleic acid (omega-6)) and increasing levels over time in mice with pre-
malignant lesions. Conclusion(s): We developed a novel high penetrance diet-induced
lean NASH-HCC mouse model. Plasma PUFA levels were reduced with tumor progression
in parallel with reduced expression of genes controlling desaturase expression
suggesting their potential use as biomarkers for lean NASH-HCC progression as well
as chemopreventive molecules.Copyright © The author(s).
sid=OVID:embase&id=pmid:&id=doi:10.7150%2Fjca.48495&issn=1837-
5546&date=2020&title=Journal+of+Cancer&atitle=Reduction+of+polyunsaturated+fatty+ac
ids+with+tumor+progression+in+a+lean+non-alcoholic+steatohepatitis-
+associated+hepatocellular+carcinoma+mouse+model&aulast=Vlock&pid=%3Cauthor
%3EVlock+E.M.%3BKaranjit+S.%3BTalmon+G.%3BFarazi+P.A.%3C%2Fauthor%3E%3CAN
<49>
Accession Number
2004839255
Title
Epidemiology of non-alcoholic fatty liver disease and non-alcoholic
steatohepatitis in Japan: A focused literature review.
Source
JGH Open. 4(5) (pp 808-817), 2020. Date of Publication: 01 Oct 2020.
Author
Eguchi Y.; Wong G.; Lee E.; Akhtar O.; Lopes R.; Sumida Y.
Institution
(Eguchi) Liver Center, Saga University Hospital, Saga University, Saga, Japan
(Wong, Lee) Gilead Sciences, Inc., Foster City, CA, United States
(Akhtar) Amaris, London, United Kingdom
(Lopes) Amaris, Barcelona, Spain
(Sumida) Division of Hepatology and Pancreatology, Department of Internal
Medicine, Aichi Medical University, Nagakute, Japan
Publisher
Subject Headings
blood pressure
body mass
body weight gain
dyslipidemia
female
glucose blood level
human
hypertension
incidence
Japan
liver cirrhosis
liver fibrosis
male
*nonalcoholic steatohepatitis/ep [Epidemiology]
obesity
prevalence
priority journal
review
systematic review
aminotransferase/ec [Endogenous Compound]
Drug Index Terms
alanine aminotransferase / endogenous compound; aminotransferase / endogenous
compound; aspartate aminotransferase / endogenous compound; high density
lipoprotein cholesterol / endogenous compound; triacylglycerol / endogenous
compound
Other Index Terms
blood pressure; body mass; body weight gain; dyslipidemia; female; glucose blood
level; human; hypertension; incidence; Japan; liver cell carcinoma; liver
cirrhosis; liver fibrosis; male; metabolic syndrome X; non insulin dependent
diabetes mellitus; *nonalcoholic fatty liver / *epidemiology; Nonalcoholic Fatty
Liver Disease Activity Score; *nonalcoholic steatohepatitis / *epidemiology;
obesity; prevalence; priority journal; Review; systematic review
Abstract
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis
(NASH) represent a growing unmet medical need and an increasingly prevalent cause
of cirrhosis, hepatocellular carcinoma (HCC), and death in Japan. The aim of this
review was to characterize the epidemiology of NAFLD and NASH in Japan. An English
and Japanese literature search was conducted in PubMed, Embase, and ICHUSHI Web,
identifying 6553 studies, 67 of which were included. Prevalence of NAFLD in the
Japanese population rose from the early 1990s (12.6-12.9%) to the early 2000s
(24.6-34.7% of the population). Japanese NASH prevalence is estimated to be 1.9-
2.7%. NAFLD and NASH are more common among males than females; however, females
experience more severe disease than males. While obese patients had higher
prevalence of NAFLD/NASH, nonobese individuals (body mass index [BMI] <25 kg/m2)
consistently comprised 20% to >35% of NAFLD and NASH patients. The evidence shows
that, despite obesity being linked with worse disease stages, "lean-NASH" also
plays an important role in NASH epidemiology. Besides obesity, diabetes and
metabolic syndrome appeared to be reliably associated with disease severity. The
prevalence of advanced fibrosis or cirrhotic disease was the highest in patients
with NASH-HCC (44-80% with stage F3/F4 disease), while 21-50% of patients with NASH
had F3/F4 disease. NAFLD/NASH is common in the Japanese population, and the
prevalence of these conditions has tripled in the last two decades. Furthermore,
these NAFLD/NASH patients have a high comorbidity burden. Early and efficient
identification of safe and effective treatments for NAFLD/NASH patients is urgently
needed.Copyright © 2020 The Authors. JGH Open: An open access journal of
gastroenterology and hepatology published by Journal of Gastroenterology and
Hepatology Foundation and John Wiley & Sons Australia, Ltd.
sid=OVID:embase&id=pmid:&id=doi:10.1002%2Fjgh3.12349&issn=2397-
817&date=2020&title=JGH+Open&atitle=Epidemiology+of+non-
alcoholic+fatty+liver+disease+and+non-alcoholic+steatohepatitis+in+Japan
%3A+A+focused+literature+review&aulast=Eguchi&pid=%3Cauthor%3EEguchi+Y.%3BWong+G.
%3BLee+E.%3BAkhtar+O.%3BLopes+R.%3BSumida+Y.%3C%2Fauthor%3E%3CAN%3E2004839255%3C
%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<50>
Accession Number
2005025281
PMID
Title
Established and emerging factors affecting the progression of nonalcoholic fatty
liver disease.
Source
Metabolism: Clinical and Experimental. 111(Supplement) (no pagination), 2020.
Article Number: 154183. Date of Publication: October 2020.
Author
Kechagias S.; Nasr P.; Blomdahl J.; Ekstedt M.
Institution
(Kechagias, Nasr, Blomdahl, Ekstedt) Department of Gastroenterology and
Hepatology, Linkoping University, Linkoping, Sweden
(Kechagias, Nasr, Blomdahl, Ekstedt) Department of Medical and Health Sciences,
Linkoping University, Linkoping, Sweden
Publisher
W.B. Saunders
Subject Headings
age
alcohol consumption
all cause mortality
article
body mass
body weight change
clinical outcome
diet composition
*disease exacerbation
disease severity
dyslipidemia
end stage liver disease
environmental factor
evidence based practice
fat intake
genetic analysis
genome-wide association study
histopathology
human
hypertension
lean body weight
liver cirrhosis
morbidity
mortality rate
nutrient
obesity
physical activity
prevalence
priority journal
risk factor
sarcopenia
alcohol
alpha 1 antitrypsin/ec [Endogenous Compound]
ferritin/ec [Endogenous Compound]
fructose
iron/ec [Endogenous Compound]
monounsaturated fatty acid
omega 3 fatty acid
omega 6 fatty acid
trans fatty acid
Drug Index Terms
alcohol; alpha 1 antitrypsin / endogenous compound; ferritin / endogenous
compound; fructose; iron / endogenous compound; monounsaturated fatty acid; omega 3
fatty acid; omega 6 fatty acid; trans fatty acid
Other Index Terms
age; alcohol consumption; all cause mortality; alpha 1 antitrypsin deficiency;
Article; body mass; body weight change; clinical outcome; diet composition;
*disease exacerbation; disease severity; dyslipidemia; end stage liver disease;
environmental factor; evidence based practice; fat intake; genetic analysis;
genetic polymorphism; genome-wide association study; histopathology; human;
hypertension; lean body weight; liver cell carcinoma; liver cirrhosis; meta
analysis (topic); metabolic syndrome X; morbidity; mortality rate; non insulin
dependent diabetes mellitus; *nonalcoholic fatty liver / *etiology; nutrient;
obesity; physical activity; prevalence; priority journal; risk factor; sarcopenia;
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver
disease affecting approximately 25% of the global population. Although a majority
of NAFLD patients will never experience liver-related symptoms it is estimated that
5-10% will develop cirrhosis-related complications with risk of death or need for
liver transplantation. NAFLD is closely associated with cardiovascular disease and
components of the metabolic syndrome. However, NAFLD is not uncommon in lean
individuals and may in these subjects represent a different entity with separate
pathophysiological mechanisms involved implying a higher risk for development of
end-stage liver disease. There is considerable fluctuation in the histopathological
course of NAFLD that may partly be attributed to lifestyle factors and dietary
composition. Nutrients such as fructose, monounsaturated fatty acids, and trans-
fatty acids may aggravate NAFLD. Presence of type 2 diabetes mellitus seems to be
the most important clinical predictor of liver-related morbidity and mortality in
NAFLD. Apart from severity of the metabolic syndrome, genetic polymorphisms and
environmental factors, such as moderate alcohol consumption, may explain the
variation in histopathological and clinical outcome among NAFLD patients.Copyright
© 2020 Elsevier Inc.
sid=OVID:embase&id=pmid:32061907&id=doi:10.1016%2Fj.metabol.2020.154183&issn=0026-
0495&isbn=&volume=111&issue=Supplement&spage=154183&pages=&date=2020&title=Metaboli
sm
%3A+Clinical+and+Experimental&atitle=Established+and+emerging+factors+affecting+the
+progression+of+nonalcoholic+fatty+liver+disease&aulast=Kechagias&pid=%3Cauthor
%3EKechagias+S.%3BNasr+P.%3BBlomdahl+J.%3BEkstedt+M.%3C%2Fauthor%3E%3CAN
<51>
Accession Number
2004811541
PMID
Title
Metabolic syndrome is not uncommon among lean non-alcoholic fatty liver disease
patients as compared with those with obesity.
Source
Indian Journal of Gastroenterology. 39(1) (pp 75-83), 2020. Date of Publication:
01 Feb 2020.
Author
Sinha N.; Mukhopadhyay S.; Sau M.
Institution
(Sinha, Sau) Community Medicine, Midnapore Medical College, Midnapore 721 101,
India
(Mukhopadhyay) Department of General Medicine, Ramakrishna Mission Seva
Pratishthan, Vivekananda Institute of Medical Sciences, Kolkata 700 026, India
Publisher
Springer
Subject Headings
adult
anthropometry
article
body mass
cardiovascular risk
color Doppler flowmetry
controlled study
diastolic blood pressure
disease association
echocardiography
echography
electrocardiography
female
glucose blood level
human
International Diabetes Federation
male
middle aged
*obesity
observational study
prevalence
prospective study
risk factor
systolic blood pressure
waist circumference
high density lipoprotein/ec [Endogenous Compound]
low density lipoprotein/ec [Endogenous Compound]
low density lipoprotein cholesterol/ec [Endogenous Compound]
uric acid/ec [Endogenous Compound]
Drug Index Terms
endogenous compound; C reactive protein / endogenous compound; cholesterol /
endogenous compound; hemoglobin A1c / endogenous compound; high density lipoprotein
/ endogenous compound; high density lipoprotein cholesterol / endogenous compound;
low density lipoprotein / endogenous compound; low density lipoprotein
cholesterol / endogenous compound; triacylglycerol / endogenous compound; uric acid
/ endogenous compound
Other Index Terms
adult; anthropometry; Article; body mass; cardiovascular risk; color Doppler
flowmetry; controlled study; cross-sectional study; diastolic blood pressure;
disease association; disease exacerbation; echocardiography; echography;
electrocardiography; female; glucose blood level; human; International Diabetes
Federation; major clinical study; male; *metabolic syndrome X; middle aged;
*nonalcoholic fatty liver; *obesity; observational study; prevalence; prospective
study; risk factor; systolic blood pressure; waist circumference
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity,
which is known to be associated with metabolic syndrome (MS). However, the risk
factors for NAFLD in absence of obesity (leanness) is not well-studied. This study
aimed to investigate and compare the clinical characteristics, metabolic
associations, and cardiovascular risk factors among patients having NAFLD with
(body mass index [BMI] >= 23 kg/m2) or without obesity (BMI < 23 kg/m2). Method(s):
The cross-sectional study was conducted among the outdoor and indoor patients
diagnosed as NAFLD by ultrasonography in a tertiary care teaching hospital in
eastern India. Relevant anthropometric measurements, laboratory investigations, and
imaging were performed. Metabolic syndrome was classified by the "International
Diabetes Federation, 2005" criteria. Result(s): Among 120 NAFLD patients, 37
(30.8%) were lean, while 83 (69.2%) were obese. The components of MS such as
systolic blood pressure (lean, 138.0 +/- 17.6 mmHg; obese, 137.9 +/- 15.3 mmHg),
diastolic blood pressure (lean, 88.9 +/- 6.5 mmHg; obese, 87.3 +/- 6.1 mmHg),
fasting blood sugar (lean, 127.8 +/- 30.8 mg/dL; obese, 135.1 +/- 29.5 mg/dL), and
serum triglyceride (lean, 170.5 +/- 34.2 mg/dL; obese, 186.4 +/- 43.8 mg/dL) were
comparable among patients with obese and lean NAFLD and were more often abnormal
among both the groups of NAFLD as compared with controls. Conclusion(s): The
overall prevalence of MS among NAFLD study population was 64.2%. Lean NAFLD was
also associated with the component of MS like obese NAFLD.Copyright © 2020, Indian
Society of Gastroenterology.
83&date=2020&title=Indian+Journal+of+Gastroenterology&atitle=Metabolic+syndrome+is+
not+uncommon+among+lean+non-
alcoholic+fatty+liver+disease+patients+as+compared+with+those+with+obesity&aulast=S
inha&pid=%3Cauthor%3ESinha+N.%3BMukhopadhyay+S.%3BSau+M.%3C%2Fauthor%3E%3CAN
<52>
Accession Number
2004442502
PMID
Title
Epidemiology of non-alcoholic fatty liver disease in Asia.
Source
Indian Journal of Gastroenterology. 39(1) (no pagination), 2020. Date of
Publication: 01 Feb 2020.
Author
Wong S.-W.; Chan W.-K.
Author NameID
Chan, Wah-Kheong; ORCID: https://orcid.org/0000-0002-9105-5837
Institution
(Wong, Chan) Gastroenterology and Hepatology Unit, Department of Medicine,
Faculty of Medicine, University Malaya, Kuala Lumpur 50603, Malaysia
Publisher
Springer
Subject Headings
Asia
Barrett esophagus
body mass
caloric intake
Child Pugh score
chronic hepatitis B
disease severity
familial hypercholesterolemia
follow up
glucose blood level
glycemic control
health care cost
hepatic encephalopathy
Hepatitis C virus
human
insulin resistance
liver biopsy
nuclear magnetic resonance spectroscopy
obesity
prevalence
prospective study
review
risk factor
systematic review
transient elastography
virus load
apolipoprotein B/ec [Endogenous Compound]
hepatitis B surface antigen/ec [Endogenous Compound]
Drug Index Terms
alanine aminotransferase / endogenous compound; apolipoprotein B / endogenous
compound; bilirubin / endogenous compound; hemoglobin A1c / endogenous compound;
hepatitis B surface antigen / endogenous compound
Other Index Terms
Asia; Barrett esophagus; body mass; caloric intake; Child Pugh score; chronic
hepatitis B; disease severity; familial hypercholesterolemia; follow up; glucose
blood level; glycemic control; health care cost; hepatic encephalopathy; Hepatitis
C virus; human; insulin resistance; liver biopsy; metabolic syndrome X; non insulin
dependent diabetes mellitus; *nonalcoholic fatty liver; nuclear magnetic resonance
spectroscopy; obesity; prevalence; prospective study; Review; risk factor;
systematic review; transient elastography; virus load
Abstract
The growing burden of non-alcoholic fatty liver disease (NAFLD) parallels the
increasing prevalence of obesity in Asia. The overall prevalence of NAFLD in Asia
is now estimated to be 29.6% and may have surpassed that in Western populations.
NAFLD increases with increasing age and is closely associated with metabolic
syndrome. Ethnic differences exist in the prevalence of NAFLD, but the underlying
factors are unclear. There were initial concerns about lean NAFLD being associated
with more severe liver disease and increased mortality, but subsequent studies
suggested otherwise. Only some NAFLD patients progress to develop advanced liver
fibrosis and cirrhosis, while the liver status remains unchanged in the majority;
fibrosis stage is the most important predictor of disease-specific mortality in
NAFLD. Surveillance for hepatocellular carcinoma (HCC) remains a challenge due to
undiagnosed cirrhosis and the development of HCC in non-cirrhotic NAFLD patients.
Diabetes mellitus shares a bidirectional relationship with NAFLD; NAFLD is highly
prevalent among patients with diabetes mellitus, and diabetes mellitus is
associated with more severe NAFLD. Chronic hepatitis B (CHB) is a major cause of
chronic liver disease in Asia; NAFLD and CHB are increasingly observed together
because of the increasing prevalence of NAFLD. Despite studies reporting favorable
virologic outcome in CHB patients with NAFLD, NAFLD has been found to be
independently associated with fibrosis progression and poorer prognosis in CHB
patients. Therefore, NAFLD in CHB patients should be given more attention.Copyright
© 2020, Indian Society of Gastroenterology.
sid=OVID:embase&id=pmid:32152903&id=doi:10.1007%2Fs12664-020-01018-x&issn=0254-
8860&isbn=&volume=39&issue=1&spage=1&pages=&date=2020&title=Indian+Journal+of+Gastr
oenterology&atitle=Epidemiology+of+non-
alcoholic+fatty+liver+disease+in+Asia&aulast=Wong&pid=%3Cauthor%3EWong+S.-W.
%3BChan+W.-K.%3C%2Fauthor%3E%3CAN%3E2004442502%3C%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<53>
Accession Number
2002413431
PMID
Title
High Risk of Fatty Liver Disease Amplifies the Alanine Transaminase-Lowering
Effect of a HSD17B13 Variant.
Source
Hepatology. 71(1) (pp 56-66), 2020. Date of Publication: 01 Jan 2020.
Author
Gellert-Kristensen H.; Nordestgaard B.G.; Tybjaerg-Hansen A.; Stender S.
Author NameID
Stender, Stefan; ORCID: https://orcid.org/0000-0003-0281-5900
Institution
(Gellert-Kristensen, Tybjaerg-Hansen, Stender) Department of Clinical
Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
(Nordestgaard) Department of Clinical Biochemistry, Herlev and Gentofte Hospital,
Copenhagen University Hospitals, Copenhagen, Denmark
(Nordestgaard, Tybjaerg-Hansen) The Copenhagen General Population Study, Herlev
and Gentofte Hospital, Copenhagen University Hospitals, Copenhagen, Denmark
(Nordestgaard, Tybjaerg-Hansen) The Copenhagen City Heart Study, Bispebjerg and
Frederiksberg Hospital, Copenhagen University Hospitals, Copenhagen, Denmark
(Nordestgaard, Tybjaerg-Hansen) Faculty of Health and Medical Sciences,
University of Copenhagen, Copenhagen, Denmark
Publisher
John Wiley and Sons Inc. (P.O.Box 18667, Newark NJ 07191-8667, United States)
Subject Headings
adult
aged
*alcohol consumption
all cause mortality
article
diabetes mellitus
*enzyme blood level
*fatty liver/et [Etiology]
female
gene frequency
genetic association
*genetic risk
genotype
heavy drinker
heterozygote
high risk population
homozygote
human
lean body weight
liver cirrhosis
*loss of function mutation
male
non-drinker
*obesity
pathogenesis
priority journal
prospective study
sex difference
*alanine aminotransferase/ec [Endogenous Compound]
alkaline phosphatase/ec [Endogenous Compound]
*hydroxysteroid dehydrogenase/ec [Endogenous Compound]
protein/ec [Endogenous Compound]
unclassified drug
*hydroxysteroid 17 beta dehydrogenase 13/ec [Endogenous Compound]
patatin like phospholipase domain containing protein 3/ec [Endogenous Compound]
transmembrane 6 superfamily 2/ec [Endogenous Compound]
Candidate Terms
*hydroxysteroid 17 beta dehydrogenase 13 / *endogenous compound [drug term]
patatin like phospholipase domain containing protein 3 / endogenous compound
[drug term]
transmembrane 6 superfamily 2 / endogenous compound [drug term]
Drug Index Terms
*alanine aminotransferase / *endogenous compound; alkaline phosphatase /
endogenous compound; aspartate aminotransferase / endogenous compound; bilirubin /
endogenous compound; *hydroxysteroid dehydrogenase / *endogenous compound;
protein / endogenous compound; unclassified drug
Other Index Terms
adult; aged; *alcohol consumption; all cause mortality; Article; diabetes
mellitus; *enzyme blood level; *fatty liver / *etiology; female; gene frequency;
genetic association; *genetic risk; genotype; heavy drinker; heterozygote; high
risk population; homozygote; human; lean body weight; liver cell carcinoma; liver
cirrhosis; *loss of function mutation; major clinical study; male; non-drinker;
*obesity; pathogenesis; priority journal; prospective study; sex difference
Abstract
A common loss-of-function variant in HSD17B13 (rs72613567:TA) was recently found
to protect from chronic liver disease. Whether the variant confers protection from
specific risk factors for liver disease is unclear. We tested the association of
rs72613567 with plasma levels of alanine transaminase (ALT) and clinical liver
disease and mortality in 111,612 individuals from the Danish general population,
including 497 with cirrhosis and 113 with hepatocellular carcinoma. HSD17B13
rs72613567:TA was associated with stepwise lower levels of plasma ALT of up to 1.3
U/L in TA/TA homozygotes versus T/T homozygotes. For each TA-allele, the risk of
cirrhosis and hepatocellular carcinoma was reduced by 15% and 28%, respectively. In
prospective analyses, the TA-allele was associated with up to 33% lower rates of
liver-related mortality in the general population, and with up to 49% reduced
liver-related mortality in patients with cirrhosis. The ALT-lowering effect of
rs72613567:TA was amplified by increasing adiposity, alcohol consumption, and
genetic risk of fatty liver disease. The TA-allele was associated with only
marginally lower ALT in lean nondrinkers with low genetic risk of hepatic
steatosis. In contrast, compared with T/T homozygotes, TA/TA homozygotes had 12% to
carrying three or four steatogenic alleles in patatin-like phospholipase domain-
containing protein 3 (PNPLA3) and transmembrane 6 superfamily 2 (TM6SF2).
Conclusion(s): High risk of fatty liver disease amplifies the ALT-lowering effect
of HSD17B13 rs72613567:TA in the Danish general population.Copyright © 2019 by the
American Association for the Study of Liver Diseases.
66&date=2020&title=Hepatology&atitle=High+Risk+of+Fatty+Liver+Disease+Amplifies+the
+Alanine+Transaminase-Lowering+Effect+of+a+HSD17B13+Variant&aulast=Gellert-
Kristensen&pid=%3Cauthor%3EGellert-Kristensen+H.%3BNordestgaard+B.G.%3BTybjaerg-
Hansen+A.%3BStender+S.%3C%2Fauthor%3E%3CAN%3E2002413431%3C%2FAN%3E%3CDT%3EArticle
%3C%2FDT%3E
<54>
Accession Number
633902188
Title
An energy restriction-weight loss intervention is able to reverse the expression
of tumour-promoting genes in liver induced by an obese microenvironment.
Source
Obesity Reviews. Conference: European and International Congress on Obesity,
ECOICO 2020. Virtual. 21(SUPPL 1) (no pagination), 2020. Date of Publication: 2020.
Author
Izquierdo A.; Carreira M.; Fernandez Quintela A.; Portillo M.; Casanueva F.;
Crujeiras A.
Institution
(Izquierdo, Crujeiras) Epigenomics in Endocrinology and Nutrition group,
Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de
Santiago (CHUS), Madrid, Spain
(Carreira, Casanueva) Laboratory of Molecular and Cellular Endocrinology,
Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de
Santiago (CHUS), Santiago de Compostela, Spain
(Fernandez Quintela, Portillo) Nutrition and Obesity Group, Department of
Nutrition and Food Science, University of the Basque Country (UPV/EHU), Vitoria,
Spain
Publisher
Subject Headings
adult
animal experiment
animal model
*body weight loss
cancer inhibition
cell proliferation
conference abstract
controlled study
fat mass
*fatty liver
food intake
genetic marker
inflammation
lipid liver level
liver dysfunction
male
*microenvironment
nonhuman
*obesity
oxidative stress
rat
rat model
treadmill
trunk
8 hydroxydeoxyguanosine
antioxidant
endogenous compound
glutathione transferase M2
interleukin 10
interleukin 6
protein p53
sirtuin 1
survivin
transforming growth factor beta
triacylglycerol
tumor necrosis factor
vasculotropin
Drug Index Terms
8 hydroxydeoxyguanosine; antioxidant; endogenous compound; glutathione
transferase M2; interleukin 10; interleukin 6; monocyte chemotactic protein 1;
protein p53; sirtuin 1; survivin; transforming growth factor beta; triacylglycerol;
tumor necrosis factor; vasculotropin
Other Index Terms
adult; animal experiment; animal model; *body weight loss; cancer inhibition;
cell proliferation; conference abstract; controlled study; fat mass; *fatty liver;
food intake; genetic marker; genetic susceptibility; inflammation; lipid liver
level; *liver carcinogenesis; liver cell carcinoma; liver dysfunction; male;
*microenvironment; nonhuman; *obesity; oxidative stress; rat; rat model; treadmill;
trunk
Abstract
INTRODUCTION: The epidemiological evidences regarding to the association between
obesity and several types of cancer, such as hepatocellular carcinoma, highlight
the necessity to investigate whether obesity itself could induce a differential
expression of genes commonly associated with the initial phase of liver
tumorigenesis, which could be reversed after weight loss. In this study used a
tumorfree rat model of obesity to investigate whether obese microenvironment could
induce a differential expression of tumour-promoting genes and to explore whether
these changes can be reversed after a weight loss intervention with energy
restriction and/or exercise. METHOD(S): The liver and trunk blood were isolated
from male young (6-week old) and adult (20-week old) obese Zucker (fa/fa; n = 10
young, 40 adult) rats and the lean group (Fa/-; n = 10 young, 10 adult). Throughout
the last 4 weeks of the experimental period, a set of adult obese rats (n = 30)
underwent a weight-loss protocol of energy restriction (30% less in quantity than
their individual food intake) and/or exercise (30 min/day at 20 m/min in rodent
treadmill). The treated animals were compared with an obese ab libitum group. We
analysed liver carcinogenesis-related genes and some parameters associated with
liver dysfunction, such as grade of hepatic steatosis, liver triacylglycerol
content, oxidative stress and inflammation markers. RESULT(S): At the end of the
experimental period, a dysregulation of the liver carcinogenesis-related genes
(Survivin/BIRC5, GST-M2, SIRT1, TGFB, TP53) was observed in association with liver
dysfunction parameters as well as, oxidative stress (MDA, AOP, 8-OHdG) and
inflammation markers (TNFalpha, VEGF, IL-6, IL-10, MCP-1). Relevantly, after weight
loss induced by energy restriction in obese rats, the effect on liver
carcinogenesis-related genes was reversed concomitantly with a reduction in fat
mass, hepatic lipid content, oxidative stress and inflammation. CONCLUSION(S): Our
results indicates that excess adipose tissue is accompanied by a dysregulation of
genes involved in cancer development mechanisms, such as cellular proliferation,
antioxidant protection and tumour suppression. This effect on the gene regulation
was related to oxidative stress and inflammation parameters. These findings are
clinically relevant because it was detectable in the liver without evidence of
tumoral mass and it was reversed after weight loss. Consequently, this study
evidences the susceptibility of obese individuals to the initiation of a
hepatocarcinogenic process that can be prevented by promoting a healthy body
weight.
sid=OVID:embase&id=pmid:&id=doi:10.1111%2Fobr.13118&issn=1467-
789X&isbn=&volume=21&issue=SUPPL+1&spage=&pages=&date=2020&title=Obesity+Reviews&at
itle=An+energy+restriction-
weight+loss+intervention+is+able+to+reverse+the+expression+of+tumour-
promoting+genes+in+liver+induced+by+an+obese+microenvironment&aulast=Izquierdo&pid=
%3Cauthor%3EIzquierdo+A.%3BCarreira+M.%3BFernandez+Quintela+A.%3BPortillo+M.
%3BCasanueva+F.%3BCrujeiras+A.%3C%2Fauthor%3E%3CAN%3E633902188%3C%2FAN%3E%3CDT
<55>
Accession Number
633631477
Title
An improved diet-induced murine model for nonalcoholic fatty liver disease with
rapid progression of steatohepatitis and fibrosis.
Source
Hepatology. Conference: 71st Annual Meeting of the American Association for the
Study of Liver Diseases, AASLD. Boston, MA United States. 72(1 SUPPL) (pp 317A),
2020. Date of Publication: November 2020.
Author
Nakamura M.; Chiba T.; Sakuma T.; Iwanaga T.; Fujita N.; Ao J.; Ma Y.; Kanayama
K.; Kanzaki H.; Koroki K.; Kobayashi K.; Nakagawa R.; Kanogawa N.; Kiyono S.; Kondo
T.; Saito T.; Ogasawara S.; Ooka Y.; Suzuki E.; Nakamoto S.; Muroyama R.; Kato N.
Institution
(Nakamura, Chiba, Sakuma, Iwanaga, Fujita, Ao, Ma, Kanayama, Kanzaki, Koroki,
Kobayashi, Nakagawa, Kanogawa, Kiyono, Kondo, Saito, Ogasawara, Ooka, Suzuki,
Nakamoto, Muroyama, Kato) Department of Gastroenterology, Graduate School of
Medicine, Chiba University
Publisher
Subject Headings
adult
animal experiment
animal model
animal tissue
body weight gain
C57BL 6 mouse
*chow diet
colic
conference abstract
controlled study
gene expression
*histology
histopathology
inflammation
KK-Ay mouse
liver cell
*liver fibrosis
liver weight
male
mouse
*murine model
nonhuman
obesity
protein expression
real time polymerase chain reaction
endogenous compound
fructose
low density lipoprotein cholesterol
smooth muscle actin
tumor necrosis factor
Drug Index Terms
endogenous compound; fructose; low density lipoprotein cholesterol; monocyte
chemotactic protein 1; smooth muscle actin; transforming growth factor beta; tumor
necrosis factor
Other Index Terms
adult; alanine aminotransferase blood level; animal experiment; animal model;
animal tissue; body weight gain; C57BL 6 mouse; *chow diet; colic; conference
abstract; controlled study; gene expression; *histology; histopathology;
inflammation; KK-Ay mouse; liver cell; *liver fibrosis; liver weight; male; mouse;
*murine model; non insulin dependent diabetes mellitus; *nonalcoholic fatty liver;
nonhuman; obesity; protein expression; real time polymerase chain reaction
Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) become a major cause of
chronic liver disease worldwide NAFLD often develop steatohepatitis, which can lead
to cirrhosis and hepatocellular carcinoma Although the conquest of NAFLD is a great
mission to be accomplished, treatment options for NAFLD remain limited The lack of
a standardized animal model that recapitulates human disease is one of the barriers
to establish a treatment Dietary models are generally preferable as preclinical
models because they do not rely on one specific gene knockout. However, many diet-
induced murine models need long term to develop steatohepatitis and fibrosis. In
this study, we aimed to develop an improved murine model for NAFLD with rapid
progression of steatohepatitis and fibrosis. Method(s): Male KK-Ay/TaJcl mice,
which developed type 2 diabetes and obesity, were used in this study Male
C57BL/6JJcl mice were also used as a non-diabetic control Mice (6-week-old) were
fed with a normal chow diet or a NAFLD diet containing high fat, high cholesterol,
high fructose and colic acid Mice were euthanized at 4 and 12 weeks Liver and serum
samples were collected and processed for histological, serological and gene
expression analysis The expression levels of genes were assessed by real-time PCR
with DELTADELTACT methods. Result(s): Significant weight gain was observed in KK-Ay
mice fed with NAFLD diet (KK/NAFLD) but not in B6 mice fed with NAFLD diet
(B6/NAFLD) KK/ NAFLD showed marked increase of liver weight and liver to body
weight ratio, compared to B6/NAFLD Serum ALT was elevated at 4 and 12 weeks,
especially in KK/NAFLD Serum LDL-C was also elevated at 4 and 12 weeks in KK/NAFLD
and B6/NAFLD. Histologically, steatosis, inflammation and hepatocyte ballooning
were observed at 4 and 12 weeks in KK/NAFLD and B6/NAFLD. Liver fibrosis were
observed at 12 weeks in both groups. The expressions of inflammatory genes (such as
TNFa, CCL2 and F4/80) and fibrotic genes (such as TGFbeta, ACTA2, TIPM1 and COL1A1)
were highly upregulated at 4 and 12 weeks in KK/NAFLD and B6/NAFLD Conclusion(s):
These murine model rapidly developed steatohepatitis and liver fibrosis. Taking
into consideration a marked increase of body weight and liver weight, KK-Ay-based
model could be useful for study of obese NAFLD In contrast, C57BL/6-based model
might be useful as a model for lean NAFLD.
3350&isbn=&volume=72&issue=1+SUPPL&spage=317A&pages=317A&date=2020&title=Hepatology
&atitle=An+improved+diet-
induced+murine+model+for+nonalcoholic+fatty+liver+disease+with+rapid+progression+of
+steatohepatitis+and+fibrosis&aulast=Nakamura&pid=%3Cauthor%3ENakamura+M.
%3BChiba+T.%3BSakuma+T.%3BIwanaga+T.%3BFujita+N.%3BAo+J.%3BMa+Y.%3BKanayama+K.
%3BKanzaki+H.%3BKoroki+K.%3BKobayashi+K.%3BNakagawa+R.%3BKanogawa+N.%3BKiyono+S.
%3BKondo+T.%3BSaito+T.%3BOgasawara+S.%3BOoka+Y.%3BSuzuki+E.%3BNakamoto+S.
%3BMuroyama+R.%3BKato+N.%3C%2Fauthor%3E%3CAN%3E633631477%3C%2FAN%3E%3CDT
<56>
Accession Number
633630007
Title
Targeting TGF-beta signaling for obesity/insulin resistance-associated
hepatocellular carcinoma.
Source
Cancer Research. Conference: American Association for Cancer Research Annual
Meeting, AACR 2020. Philadelphia, PA United States. 80(16 SUPPL) (no pagination),
Author
Chen J.; Su X.; Rojas A.; Bresalier R.S.; Stroehlein J.R.; Yeung S.-C.
Institution
(Chen, Su, Rojas, Bresalier, Stroehlein, Yeung) UT MD Anderson Cancer Center,
Houston, TX, United States
Publisher
American Association for Cancer Research Inc.
Subject Headings
animal cell
animal experiment
animal model
animal tissue
*body weight gain
cancer resistance
conference abstract
controlled study
drug therapy
drug toxicity
fatty liver
genetic background
heterozygosity
human
*insulin resistance
knockout gene
knockout mouse
leukocyte migration
liver development
male
mouse
mouse model
nonhuman
*obesity
protein function
RNA sequencing
signal transduction
*TGF beta signaling
carcinogen
diethylnitrosamine
endogenous compound
insulin
lipid
Smad3 protein
transforming growth factor beta receptor 2
Drug Index Terms
carcinogen; diethylnitrosamine; endogenous compound; insulin; lipid; Smad3
protein; transforming growth factor beta; transforming growth factor beta receptor
2
Other Index Terms
animal cell; animal experiment; animal model; animal tissue; *body weight gain;
cancer resistance; conference abstract; controlled study; drug therapy; drug
toxicity; fatty liver; genetic background; genetic susceptibility; heterozygosity;
human; *insulin resistance; knockout gene; knockout mouse; leukocyte migration;
liver carcinogenesis; *liver cell carcinoma; liver development; male; mouse; mouse
model; nonhuman; *obesity; protein function; RNA sequencing; signal transduction;
*TGF beta signaling
Abstract
Background: Recently, obesity, insulin resistance/type 2 diabetes mellitus and
fatty liver disease, i. e., key components of the metabolic syndrome, have been
recognized as risk factors for hepatocellular carcinoma (HCC). Obesity and
dysmetabolism serve as drivers of oncogenesis in the setting of abnormal hepatic
morphology and physiology, and hepatic steatosis may provide the promoting
microenvironment for the development of HCC. Dysregulated signaling in the
transforming growth factor (TGF)-beta pathway plays a central role in
immunomodulation, inflammation, and fibrogenesis in the HCC microenvironment. We
used a carcinogen Diethylnitrosamine (DEN)-induced HCC mouse model in genetically
obese mice [heterozygous Agouti yellow (A /a)] and haplo-knock out of Smad3+/-(a
kinase downstream of type II receptor for TGFbeta to study the detailed mechanism
by which Smad3-dependent TGF-beta signaling regulates obesity-associated
dysmetabolism in HCC, and to determine whether inhibition of TGF-beta signaling
could inhibit obesity-associated HCC. Method(s): A /a mice in C57B/L genetic
background were bred with Smad3+/-knockout mouse (Smad3+/-). Obese and insulin-
resistant A /a mice were treated with DEN (i. p. 25mg/kg) at 14 days of age to
induce HCC. A /a mice and DEN-induce HCC mice were treated with TGF-beta receptor 2
inhibitor (EW7919, 20 mg/kg orally 3 times/week for 8 weeks). We performed RNA
sequencing analysis for 40 mouse liver samples from the groups of mice above.
Result(s): 1. Haplodeficiency of Smad3+/-significantly decreased obesity A /a mouse
weight and suppressed fatty liver development. 2. Treatment of TGF-beta receptor 2
inhibitor to A mice successfully blocked weight gain in A /a mice. 3. DEN-induced
hepatocarcinogenesis in A /a mice occurred significantly earlier than in lean (a/a)
C57B/L mice. 4. Inhibition of TGF-beta signaling by Smad3+/-haplodeficiency
significantly upregulated lipid catabolic processes and downregulated cytokine-
induce leukocyte migration in the fatty livers of A /a mice. 5. Inhibition of TGF-
beta signaling by genetic or pharmacologic inhibitors significantly suppressed HCC
development in A /a mice. Conclusion(s): We demonstrated a specific cancer
promoting role of TGF-beta in metabolic reprogramming in liver cancer cells,
highlighting the TGF-beta signaling pathway as a potential therapeutic target in
obesity/insulin resistanceassociated HCC.
sid=OVID:embase&id=pmid:&id=doi:10.1158%2F1538-7445.AM2020-3054&issn=1538-
7445&isbn=&volume=80&issue=16+SUPPL&spage=3054&pages=&date=2020&title=Cancer+Resear
ch&atitle=Targeting+TGF-beta+signaling+for+obesity%2Finsulin+resistance-
associated+hepatocellular+carcinoma&aulast=Chen&pid=%3Cauthor%3EChen+J.%3BSu+X.
%3BRojas+A.%3BBresalier+R.S.%3BStroehlein+J.R.%3BYeung+S.-C.%3C%2Fauthor%3E%3CAN
<57>
Accession Number
633629700
Title
The epidemiology of NAFLD and lean NAFLD in Japan: A systematic review and meta-
analysis with individual patient level data and forecasting, 1995-2040.
Source
Hepatology. Conference: 71st Annual Meeting of the American Association for the
Study of Liver Diseases, AASLD. Boston, MA United States. 72(1 SUPPL) (pp 999A),
2020. Date of Publication: November 2020.
Author
Ito T.; Ishigami M.; Zou B.; Tanaka T.; Takahashi H.; Kurosaki M.; Maeda M.;
Naing Thin K.; Tanaka K.; Takahashi Y.; Itoh Y.; Oniki K.; Seko Y.; Saruwatari J.;
Kawanaka M.; Atsukawa M.; Hyogo H.; Ono M.; Ogawa E.; Barnett S.D.; Stave C.D.;
Cheung R.; Fujishiro M.; Eguchi Y.; Toyoda H.; Nguyen M.H.
Institution
(Ito, Ishigami, Tanaka, Fujishiro) Department of Gastroenterology and Hepatology,
Nagoya University, Graduate School of Medicine
(Zou, Maeda, Naing Thin, Barnett, Cheung, Nguyen) Division of Gastroenterology
and Hepatology, Department of Medicine, Stanford University Medical Center
(Takahashi, Tanaka, Eguchi) Division of Metabolism and Endocrinology, Faculty of
Medicine, Saga University
(Takahashi, Eguchi) Liver Center, Saga University Hospital
(Kurosaki, Takahashi) Department of Gastroenterology and Hepatology, Musashino
Red Cross Hospital
(Naing Thin) Yangon Specialty Hospital
(Itoh, Seko) Department of Molecular Gastroenterology and Hepatology, Kyoto
Prefectural University of Medicine
(Oniki, Saruwatari) Division of Pharmacology and Therapeutics, Graduate School of
Pharmaceutical Sciences, Kumamoto University
(Kawanaka) General Internal Medicine2, Kawasaki Medical Center, Kawasaki Medical
School
(Atsukawa) Division of Gastroenterology and Hepatology, Nippon Medical School
(Hyogo) Gastroenterology and Hepatology, JA Hiroshima General Hospital
(Ono) Department of Internal Medicine, Tokyo Women's Medical University Medical
Center East
(Ogawa) Department of General Internal Medicine, Kyushu University Hospital
(Stave) Lane Medical Library, Stanford University, School of Medicine
(Cheung) Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto
Health Care
(Toyoda) Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital
Publisher
Subject Headings
aged
all cause mortality
body mass
Cochrane Library
cohort analysis
comorbidity
conference abstract
controlled study
disease simulation
Embase
epidemic
female
*forecasting
human
incidence
*Japan
male
Medline
meta analysis
obesity
patient coding
prevalence
productivity
systematic review
waist circumference
Web of Science
Other Index Terms
aged; all cause mortality; body mass; Cochrane Library; cohort analysis;
comorbidity; conference abstract; controlled study; disease simulation; Embase;
epidemic; female; *forecasting; human; incidence; *Japan; male; Medline; meta
analysis; *nonalcoholic fatty liver; obesity; patient coding; prevalence;
productivity; systematic review; waist circumference; Web of Science
Abstract
Background: NAFLD affects about one-third of the U S population and is
increasingly recognized in Asia including Japan, despite its lower obesity rate
However, NAFLD can occur in lean people, but data on lean NAFLD are limited Using a
systematic review and meta-analytic approach with an individual patient data meta-
analysis (IPDMA) component, we aimed to investigate the prevalence, incidence, and
outcomes of NAFLD in Japan with a focus on lean NAFLD Using Bayesian modeling, we
also forecasted the future Japan NAFLD prevalence Methods: We searched PubMed,
Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society
from inception to May 15, 2019 for relevant full-text original research studies Two
authors independently screened and extracted the data We used a random-effects
model to generate pooled estimates We contacted authors of relevant studies to
obtain individual patient data for our IPDMA Results: We included 73 eligible
studies (258,531 persons) The overall NAFLD prevalence was 25 5% (95% CI 23 3-27
9), higher in males (P<0 001), varied by regions (P<0 001), and increased over time
(P=0 015), but not by per-person income or gross prefectural productivity From
1984-2012, NAFLD prevalence increased by 0 64% per year and was estimated to reach
39 3% in 2030 and 44 8% in 2040 by Bayesian modeling The incidence of NAFLD, HCC,
and overall mortality were 23 5 (95%CI, 17 5- 30 5), 7 6 (95%CI, 2 1-16 2), and 5 9
(95%CI, 3 5-8 9) per 1000 person-years, respectively The IPDMA included 14,887
persons from 8 cohorts (7,135 non-NAFLD, 7,752 NAFLD) and found the prevalence of
lean (BMI<23 kg/m2) NAFLD among the NAFLD cohort to be 20 7%, with lean NAFLD
persons being older, with lower waist circumference, fewer metabolic comorbidities,
lower PNPLA3 CC frequencies, higher FIB-4 index, and notably higher all-cause
mortality rate (8 29 vs 5 61 per 1000 person-years for non-lean NAFLD, P=0 02);
however, on multivariable Cox regression, lean NAFLD was not independently
associated with higher mortality, while older age, male sex, DM, and FIB4 were
(Figure) Conclusion(s): As seen in the West, NAFLD prevalence has increased in the
recent decades in Japan, with almost half of the Japan population projected to have
NAFLD by 2040 Lean NAFLD persons make up 20% of the NAFLD population in Japan and
have higher mortality than non-lean NAFLD persons Additional strategies are needed
to curtail the NAFLD epidemic including the lean population.
3350&isbn=&volume=72&issue=1+SUPPL&spage=999A&pages=999A&date=2020&title=Hepatology
&atitle=The+epidemiology+of+NAFLD+and+lean+NAFLD+in+Japan
%3A+A+systematic+review+and+meta-
analysis+with+individual+patient+level+data+and+forecasting%2C+1995-
2040&aulast=Ito&pid=%3Cauthor%3EIto+T.%3BIshigami+M.%3BZou+B.%3BTanaka+T.
%3BTakahashi+H.%3BKurosaki+M.%3BMaeda+M.%3BNaing+Thin+K.%3BTanaka+K.%3BTakahashi+Y.
%3BItoh+Y.%3BOniki+K.%3BSeko+Y.%3BSaruwatari+J.%3BKawanaka+M.%3BAtsukawa+M.
%3BHyogo+H.%3BOno+M.%3BOgawa+E.%3BBarnett+S.D.%3BStave+C.D.%3BCheung+R.
%3BFujishiro+M.%3BEguchi+Y.%3BToyoda+H.%3BNguyen+M.H.%3C%2Fauthor%3E%3CAN
<58>
Accession Number
633629682
Title
Targeting TGF-beta signaling for obesity/insulin resistance-associated
Source
Meeting, AACR 2020. Philadelphia, PA United States. 80(16 SUPPL) (no pagination),
Author
Chen J.; Su X.; Rojas A.; Bresalier R.S.; Stroehlein J.R.; Yeung S.-C.
Institution
(Chen, Su, Rojas, Bresalier, Stroehlein, Yeung) UT MD Anderson Cancer Center,
Houston, TX, United States
Publisher
Subject Headings
animal cell
animal experiment
animal model
animal tissue
*body weight gain
cancer resistance
conference abstract
controlled study
drug therapy
drug toxicity
fatty liver
genetic background
heterozygosity
human
*insulin resistance
knockout gene
knockout mouse
leukocyte migration
liver development
male
mouse
mouse model
nonhuman
*obesity
protein function
RNA sequencing
signal transduction
*TGF beta signaling
carcinogen
diethylnitrosamine
endogenous compound
insulin
lipid
Smad3 protein
transforming growth factor beta receptor 2
Drug Index Terms
carcinogen; diethylnitrosamine; endogenous compound; insulin; lipid; Smad3
protein; transforming growth factor beta; transforming growth factor beta receptor
2
Other Index Terms
animal cell; animal experiment; animal model; animal tissue; *body weight gain;
cancer resistance; conference abstract; controlled study; drug therapy; drug
toxicity; fatty liver; genetic background; genetic susceptibility; heterozygosity;
human; *insulin resistance; knockout gene; knockout mouse; leukocyte migration;
liver carcinogenesis; *liver cell carcinoma; liver development; male; mouse; mouse
model; nonhuman; *obesity; protein function; RNA sequencing; signal transduction;
*TGF beta signaling
Abstract
Background: Recently, obesity, insulin resistance/type 2 diabetes mellitus and
fatty liver disease, i. e., key components of the metabolic syndrome, have been
recognized as risk factors for hepatocellular carcinoma (HCC). Obesity and
dysmetabolism serve as drivers of oncogenesis in the setting of abnormal hepatic
morphology and physiology, and hepatic steatosis may provide the promoting
microenvironment for the development of HCC. Dysregulated signaling in the
transforming growth factor (TGF)-beta pathway plays a central role in
immunomodulation, inflammation, and fibrogenesis in the HCC microenvironment. We
used a carcinogen Diethylnitrosamine (DEN)-induced HCC mouse model in genetically
obese mice [heterozygous Agouti yellow (A /a)] and haplo-knock out of Smad3+/-(a
kinase downstream of type II receptor for TGFbeta to study the detailed mechanism
by which Smad3-dependent TGF-beta signaling regulates obesity-associated
dysmetabolism in HCC, and to determine whether inhibition of TGF-beta signaling
could inhibit obesity-associated HCC. Method(s): A /a mice in C57B/L genetic
background were bred with Smad3+/-knockout mouse (Smad3+/-). Obese and insulin-
resistant A /a mice were treated with DEN (i. p. 25mg/kg) at 14 days of age to
induce HCC. A /a mice and DEN-induce HCC mice were treated with TGF-beta receptor 2
inhibitor (EW7919, 20 mg/kg orally 3 times/week for 8 weeks). We performed RNA
sequencing analysis for 40 mouse liver samples from the groups of mice above.
Result(s): 1. Haplodeficiency of Smad3+/-significantly decreased obesity A /a mouse
weight and suppressed fatty liver development. 2. Treatment of TGF-beta receptor 2
inhibitor to A mice successfully blocked weight gain in A /a mice. 3. DEN-induced
hepatocarcinogenesis in A /a mice occurred significantly earlier than in lean (a/a)
C57B/L mice. 4. Inhibition of TGF-beta signaling by Smad3+/-haplodeficiency
significantly upregulated lipid catabolic processes and downregulated cytokine-
induce leukocyte migration in the fatty livers of A /a mice. 5. Inhibition of TGF-
beta signaling by genetic or pharmacologic inhibitors significantly suppressed HCC
development in A /a mice. Conclusion(s): We demonstrated a specific cancer
promoting role of TGF-beta in metabolic reprogramming in liver cancer cells,
highlighting the TGF-beta signaling pathway as a potential therapeutic target in
obesity/insulin resistanceassociated HCC.
7445&isbn=&volume=80&issue=16+SUPPL&spage=3054&pages=&date=2020&title=Cancer+Resear
ch&atitle=Targeting+TGF-beta+signaling+for+obesity%2Finsulin+resistance-
associated+hepatocellular+carcinoma&aulast=Chen&pid=%3Cauthor%3EChen+J.%3BSu+X.
%3BRojas+A.%3BBresalier+R.S.%3BStroehlein+J.R.%3BYeung+S.-C.%3C%2Fauthor%3E%3CAN
<59>
Accession Number
2005913128
Title
BARRIERS TO HEALTHY EATING IN DIVERSE PATIENTS WITH NONALCOHOLIC FATTY LIVER
DISEASE.
Source
Gastroenterology. Conference: Digestive Disease Week (DDW) 2020. Chicago United
States. 158(6 Supplement 1) (pp S-1427), 2020. Date of Publication: May 2020.
Author
Araya-Acero L.; Wilson S.; Dukandar J.; McLean H.; Martin A.; Castaneda S.M.;
Figueroa G.; Pearlman M.; Jones P.D.
Publisher
W.B. Saunders
Subject Headings
adult
Black person
body mass
body weight loss
Caucasian
clinical practice
cohort analysis
conference abstract
controlled study
demography
diabetes mellitus
diet
*eating
electronic medical record
exercise
female
health literacy
Hispanic
human
hyperlipidemia
hypertension
Kruskal Wallis test
language
liver cirrhosis
male
obese patient
questionnaire
self control
sex difference
stress
Other Index Terms
adult; Black person; body mass; body weight loss; Caucasian; chronic liver
disease; clinical practice; cohort analysis; conference abstract; controlled study;
demography; diabetes mellitus; diet; *eating; electronic medical record; exercise;
female; health literacy; Hispanic; human; hyperlipidemia; hypertension; Kruskal
Wallis test; language; liver cirrhosis; major clinical study; male; *nonalcoholic
fatty liver; obese patient; questionnaire; self control; sex difference; stress
Abstract
Introduction: The global epidemic of nonalcoholic fatty liver disease (NAFLD) is
fueled by increasing prevalence of obesity and diabetes. NAFLD patients are
counseled to make lifestyle modifications that lead to weight loss, such as
decreased caloric intake and increased exercise. In controlled studies, weight loss
improves hepatic steatosis, steatohepatitis and biomarkers. However, in routine
clinical practice, NAFLD patients seldom achieve sufficient weight loss to improve
disease-specific parameters. To inform a future clinic-based intervention, we
assessed barriers to healthy eating in NAFLD patients. Method(s): Since 2018, we
have enrolled patients with NAFLD and other chronic liver diseases from the
University of Miami/Jackson Memorial Hospitals into an observational longitudinal
cohort. Clinical data is extracted from the electronic medical record. We invited
NAFLD participants to complete a 14-item questionnaire published by Welsh et al.
that assesses barriers to diet and exercise and categorizes barriers into 3
factors: lack of knowledge, lack of self-control and lack of time. Individual items
are rated from 1 to 5 (1=Not at all true for me and 5=Very true for me) and the
factor score is the average of individual items. A higher score indicates more
perceived barriers to diet and exercise. Subgroups were compared using Pearson's
chi-squared or Kruskal Wallis tests. Result(s): From 1/2018 to 9/2019, 507
participants were enrolled, 127 have NAFLD and were invited to complete the diet
questionnaire, and 50 (27 male, 23 female) completed the questionnaire for a
response rate of 39%. (Figure 1) Participants who completed the survey were older
than those who did not,p<0.01. There were no other significant demographic
differences between respondents and non-respondents. The sample was predominantly
Hispanic, 62%, with 26% non-Hispanic Whites and 6% Blacks. Nine participants have
NAFLD-related HCC, 20 have NAFLD-related cirrhosis and 21 have NAFLD. Median BMI
was 31.3 kg/m2and 65% have hypertension, 55% have diabetes, and 45% have
hyperlipidemia. Respondents rated items on the lack of self-control scale the
highest, indicating increased barriers (median 2.44), followed by lack of knowledge
(median 2.25), then lack of time (median 1.75). There were no significant gender
differences. In obese participants, lack of knowledge was a greater barrier,
compared to overweight and normal weight participants, p 0.006. (Table 1) There
were no significant differences in barriers by preferred language (English vs.
Spanish), stage of liver disease (NAFLD vs. cirrhosis vs. HCC), health literacy or
perceived stress. Conclusion(s): Lack of self-control is the strongest perceived
barrier to healthy eating, consistent with results reported by Welsh et al.. Future
interventions should combine targeted education and a behavioral approach to
improve perceived self-control.Copyright © 2020
5085&isbn=&volume=158&issue=6+Supplement+1&spage=S&pages=S-
1427&date=2020&title=Gastroenterology&atitle=BARRIERS+TO+HEALTHY+EATING+IN+DIVERSE+
PATIENTS+WITH+NONALCOHOLIC+FATTY+LIVER+DISEASE&aulast=Araya-Acero&pid=%3Cauthor
%3EAraya-Acero+L.%3BWilson+S.%3BDukandar+J.%3BMcLean+H.%3BMartin+A.
%3BCastaneda+S.M.%3BFigueroa+G.%3BPearlman+M.%3BJones+P.D.%3C%2Fauthor%3E%3CAN
<60>
Accession Number
2001915197
Title
CLINICAL CHARACTERISTICS AND LONG-TERM OUTCOMES IN PATIENTS WITH NONALCOHOLIC
FATTY LIVER DISEASE (NAFLD) AMONG THE SPECTRUM OF OBESITY: A LONG-TERM LONGITUDINAL
STUDY.
Source
Gastroenterology. Conference: Digestive Disease Week, DDW 2019. San Diego United
States. 156(6 Supplement 1) (pp S-1253), 2019. Date of Publication: May 2019.
Author
Ha N.B.; Le R.H.; Trinh S.; Huynh J.; Gudapati S.; Maeda M.; Henry L.; Nguyen
M.H.
Publisher
W.B. Saunders
Subject Headings
advanced cancer
aged
alcohol consumption
Asian
body mass
*cancer patient
Caucasian
*clinical feature
controlled study
diabetes mellitus
ethnicity
female
fibrosis
follow up
Hispanic
histology
histopathology
history
human
human tissue
hypertension
incidence
liver cirrhosis
*longitudinal study
male
*morbid obesity
obese patient
*obesity
primary medical care
retrospective study
scoring system
toxic hepatitis
university hospital
endogenous compound
conference abstract
Candidate Terms
conference abstract [other term]
Drug Index Terms
endogenous compound
Other Index Terms
advanced cancer; aged; alcohol consumption; Asian; body mass; *cancer patient;
Caucasian; *clinical feature; controlled study; diabetes mellitus; disease
exacerbation; ethnicity; female; fibrosis; follow up; Hispanic; histology;
histopathology; history; human; human tissue; hypertension; incidence; liver cell
carcinoma; liver cirrhosis; *longitudinal study; major clinical study; male;
*morbid obesity; *nonalcoholic fatty liver; obese patient; *obesity; primary
medical care; retrospective study; scoring system; toxic hepatitis; university
hospital
Abstract
Purpose: NAFLD is commonly associated with obesity; however, limited data is
available on clinical characteristics and outcomes among the spectrum of obesity.
We aim to examine disease presentation and natural history of NAFLD in a U.S.
cohort from primary care and specialty clinics with long-term follow-up. Method(s):
Retrospective study of 2,470 consecutive NAFLD patients seen at a U.S. university
medical center from 1999-2014. NAFLD was diagnosed by imaging/histology. Exclusion
criteria: viral/drug-induced hepatitis, heavy alcohol use, and/or
inflammatory/genetic liver disease. Strict ethno-specific criteria of obesity were
applied for non-Asian vs Asian: lean (BMI<25 vs<23, n=237), overweight (BMI 25-
29.9 vs 23-27.4, n=754), obese (BMI 30-39.9 vs 27.5-37.4, n=1165), and morbid obese
(BMI>40 vs>37.5, n=314). Advanced liver disease included development of advanced
fibrosis/cirrhosis (histological/clinical evidence and/or noninvasive fibrosis
scoring system), decompensation, and/or hepatocellular carcinoma. Result(s):
Morbidly obese patients were more likely to be female (68% vs 47-61%, p<0.001) and
younger compared to lean, overweight, and obese patients (44+/-14 vs 51+/-17 vs
50+/-15 vs 49+/-14,p<0.001), and had higher rates of hypertension (69% vs 45-
61%,p<0.001) and diabetes (42% vs 21-37%,p<0.001). Compared to Asians, Caucasians
and Hispanics were more likely to be morbidly obese (5% vs 15% vs 17%,p<0.001).
Advanced fibrosis/cirrhosis at presentation were higher in morbidly obese patients
(20%,p<0.001) vs lean (11%), overweight (9%), and obese (10%) patients.
Multivariate analysis inclusive of sex, BMI, and ethnicity, older age (OR=1.06,
95%CI=1.05-1.07,p<0.001), morbid obesity (OR=2.87, 95%CI=1.65-5.01,p<0.001),
Hispanic (OR=1.68, 95%CI 1.22-2.33, p=002), and diabetes (OR=2.59, 95%CI=1.97-
3.41,p<0.001) were associated with the presence of advanced fibrosis/cirrhosis at
presentation. During a median follow-up 60 (6-255) months and 14,981 person-years,
12-year cumulative incidence of advanced liver disease was highest among morbidly
obese patients (42% vs 20% in obese, 16% in overweight and 14% in lean patients,
p=0.0002) (Figure 1). Among lean patients, 12-year cumulative incidence of advanced
disease were similar in Asians (13.1%) vs. Non-Asians (14.6%) (p=0.48). In
multivariate Cox proportional hazard model, morbid obesity independently predicted
higher advanced disease progression compared to lean/overweight/obesity (HR=2.24,
95%CI=1.23-3.99,p=0.01), in addition to older age (HR=1.04, 95%CI=1.03-
1.05,p<0.001), and diabetes (HR=2.64, 95%CI=1.99-3.52,p<0.001), but not sex and
ethnicity. Conclusion(s): Disease presentation and long-term outcomes differed
along the spectrum of obesity, with more advanced disease presentation and
increased rates of disease progression noted among morbidly obese patients,
particularly in those of older age and with diabetes. [Figure presented]Copyright ©
2019 AGA Institute. All rights reserved.
5085&isbn=&volume=156&issue=6+Supplement+1&spage=S&pages=S-
1253&date=2019&title=Gastroenterology&atitle=CLINICAL+CHARACTERISTICS+AND+LONG-
TERM+OUTCOMES+IN+PATIENTS+WITH+NONALCOHOLIC+FATTY+LIVER+DISEASE+%28NAFLD
%29+AMONG+THE+SPECTRUM+OF+OBESITY%3A+A+LONG-TERM+LONGITUDINAL+STUDY&aulast=Ha&pid=
%3Cauthor%3EHa+N.B.%3BLe+R.H.%3BTrinh+S.%3BHuynh+J.%3BGudapati+S.%3BMaeda+M.
%3BHenry+L.%3BNguyen+M.H.%3C%2Fauthor%3E%3CAN%3E2001915197%3C%2FAN%3E%3CDT
<61>
Accession Number
2001688437
Title
Whole-Exome Sequencing Identifies a Variant in Phosphatidylethanolamine N-
Methyltransferase Gene to be Associated With Lean-Nonalcoholic Fatty Liver Disease.
Source
Journal of Clinical and Experimental Hepatology. 9(5) (pp 561-568), 2019. Date of
Publication: September - October 2019.
Author
Bale G.; Vishnubhotla R.V.; Mitnala S.; Sharma M.; Padaki R.N.; Pawar S.C.;
Duvvur R.N.
Author NameID
Vishnubhotla, Ravikanth V.; ORCID: https://orcid.org/0000-0001-6970-0169
Sharma, Mithun; ORCID: https://orcid.org/0000-0003-4497-9209
Duvvur, Reddy N.; ORCID: https://orcid.org/0000-0001-7540-0496
Institution
(Bale, Vishnubhotla, Mitnala) Institute of Basic Sciences and Translational
Research, Asian Healthcare Foundation, Hyderabad, Telangana 500082, India
(Sharma, Padaki, Duvvur) Department of Medical Gastroenterology, Asian Institute
of Gastroenterology, Hyderabad, Telangana 500082, India
(Pawar) Department of Genetics, Osmania University, Hyderabad, Telangana, India
Publisher
Elsevier B.V.
Subject Headings
acoustic radiation force impulse imaging
adult
article
aspartate aminotransferase blood level
body mass
case control study
controlled study
DNA isolation
echography
fatty acid metabolism
female
*genetic association
*genetic variability
genotype
germ line
hip circumference
human
*lean body weight
male
middle aged
pathogenesis
priority journal
waist circumference
waist hip ratio
*whole exome sequencing
binding protein/ec [Endogenous Compound]
*phosphatidylethanolamine methyltransferase/ec [Endogenous Compound]
unclassified drug
genetic analyzer
oxysterol binding protein related protein10/ec [Endogenous Compound]
Candidate Terms
oxysterol binding protein related protein10 / endogenous compound [drug term]
Device Index Terms
genetic analyzer
Drug Index Terms
endogenous compound; binding protein / endogenous compound;
*phosphatidylethanolamine methyltransferase / *endogenous compound; triacylglycerol
/ endogenous compound; unclassified drug
Other Index Terms
acoustic radiation force impulse imaging; adult; alanine aminotransferase blood
level; Article; aspartate aminotransferase blood level; body mass; case control
study; controlled study; data analysis software; DNA isolation; echography; fatty
acid metabolism; female; *genetic association; genetic susceptibility; *genetic
variability; genotype; germ line; hip circumference; human; *lean body weight;
major clinical study; male; middle aged; *nonalcoholic fatty liver / *etiology;
pathogenesis; priority journal; real time polymerase chain reaction;
triacylglycerol blood level; waist circumference; waist hip ratio; *whole exome
sequencing
Abstract
Background and aim: Nonalcoholic fatty liver disease (NAFLD) is a spectrum of
liver diseases with simple steatosis on one end and hepatocellular carcinoma on the
other. Although obesity is a known risk factor for NAFLD, individuals with normal
body mass index (BMI) also have hepatic fatty infiltration, now termed "lean-
NAFLD". It represents a distinct entity with a strong underlying genetic component.
The present study aimed to sequence the complete exonic regions of individuals with
lean-NAFLD to identify germline causative variants associated with disrupted
hepatic fatty acid metabolism, thereby conferring susceptibility to NAFLD.
Method(s): Whole blood was collected from patients with lean-NAFLD (n = 6; BMI <
23.0 kg/m2) and matched lean controls (n = 2; discovery set). Liver fat was
assessed using acoustic radiation force impulse (ARFI) imaging. Patients with
ultrasound-detected NAFLD (n = 191) and controls (n = 105) were part of validation
set. DNA was isolated, and whole-exome sequencing (WES) was performed in the
discovery cohort (Ion ProtonTM; Ion AmpliSeqTM Exome RDY Kit). Data were analyzed
(Ion Reporter software; Life Technologies), and variants identified. Validation of
variants was carried out (Taqman probes; Real time-PCR). Student's t test and
Fisher's exact test were used to analyze the statistical significance. Result(s):
Although WES identified ~74,000 variants in individual samples, using various
pipelines. variants in genes namely phosphatidylethanolamine N-methyltransferase
(PEMT) and oxysterol-binding protein-related protein10 (OSBPL10) that have roles in
dietary choline intake and regulation of cholesterol homeostasis, respectively,
were identified (discovery set). Furthermore, significant differences were noted in
BMI (p = 0.006), waist/hip circumference (p > 0.001), waist/hip ratio (p > 0.001),
aspartate aminotransferase (p > 0.001), alanine aminotransferase (p > 0.001), and
triglycerides (p = 0.002) between patients and controls. Validation of variants
(rs7946-PEMT and rs2290532-OSBPL10) revealed that variant in PEMT but not OSBPL10
gene was associated (p = 0.04) with threefold increased risk of NAFLD in lean
individuals. Conclusion(s): Our results demonstrate the association of rs7946 with
lean-NAFLD. WES may be an effective strategy to identify causative variants
underlying lean-NAFLD.Copyright © 2019 Indian National Association for Study of the
Liver
sid=OVID:embase&id=pmid:&id=doi:10.1016%2Fj.jceh.2019.02.001&issn=0973-
568&date=2019&title=Journal+of+Clinical+and+Experimental+Hepatology&atitle=Whole-
Exome+Sequencing+Identifies+a+Variant+in+Phosphatidylethanolamine+N-
Methyltransferase+Gene+to+be+Associated+With+Lean-
Nonalcoholic+Fatty+Liver+Disease&aulast=Bale&pid=%3Cauthor%3EBale+G.
%3BVishnubhotla+R.V.%3BMitnala+S.%3BSharma+M.%3BPadaki+R.N.%3BPawar+S.C.
%3BDuvvur+R.N.%3C%2Fauthor%3E%3CAN%3E2001688437%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT
%3E
<62>
Accession Number
626297907
PMID
Title
Disease progression of nonalcoholic steatohepatitis in Taiwanese patients: A
longitudinal study of paired liver biopsies.
Source
European Journal of Gastroenterology and Hepatology. 31(2) (pp 224-229), 2019.
Date of Publication: 01 Feb 2019.
Author
Lin T.-Y.; Yeh M.-L.; Huang C.-F.; Huang C.-I.; Dai C.-Y.; Hsieh M.-H.; Chen S.-
C.; Huang J.-F.; Yu M.-L.; Chuang W.-L.
Institution
(Lin, Yeh, Huang, Huang, Dai, Hsieh, Chen, Huang, Yu, Chuang) Department of
Internal Medicine, Hepatobiliary Division, Kaohsiung Medical University Hospital,
100 Tzyou Road, Kaohsiung City 807, Taiwan (Republic of China)
(Dai, Huang, Yu, Chuang) Graduate Institute of Clinical Medicine, Taiwan
(Republic of China)
(Yeh, Huang, Dai, Hsieh, Chen, Huang, Yu, Chuang) College of Medicine, Faculty of
Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (Republic of
China)
Publisher
Lippincott Williams and Wilkins (E-mail: [email protected])
Subject Headings
adult
aged
article
body weight loss
clinical article
diabetes mellitus
*disease exacerbation
female
fibrosis
histopathology
human
liver biopsy
liver cirrhosis
longitudinal study
male
middle aged
obesity
phenotype
prevalence
priority journal
remission
retrospective study
risk factor
Taiwanese
waist circumference
C peptide/ec [Endogenous Compound]
uric acid/ec [Endogenous Compound]
Drug Index Terms
endogenous compound; C peptide / endogenous compound; cholesterol / endogenous
compound; high density lipoprotein cholesterol / endogenous compound; insulin /
endogenous compound; triacylglycerol / endogenous compound; uric acid / endogenous
compound
Other Index Terms
adult; aged; Article; body weight loss; clinical article; diabetes mellitus;
*disease exacerbation; female; fibrosis; histopathology; human; liver biopsy; liver
cell carcinoma; liver cirrhosis; longitudinal study; male; middle aged;
*nonalcoholic fatty liver / *epidemiology; Nonalcoholic Fatty Liver Disease
Activity Score; obesity; phenotype; prevalence; priority journal; remission;
retrospective study; risk factor; Taiwanese; waist circumference
Abstract
Objectives Nonalcoholic steatohepatitis (NASH) might progress to fibrosis,
cirrhosis, and hepatocellular carcinoma. However, the natural history of NASH has
not been fully clarified. This study aimed to investigate the disease progression
in NASH patients receiving paired liver biopsies. We also aimed to examine the
factors associated with NASH progression. Patients and methods Ten NASH patients
who had received liver biopsies during June 2001 and February 2010 were
consecutively enrolled. The histopathological changes were examined
retrospectively, including nonalcoholic fatty liver disease activity score (NAS)
and fibrosis stage. The associated clinical profiles were also analyzed. Results
The median duration between paired biopsies was 20.5 months (range: 12-106 months).
According to NAS and fibrosis stage, disease progression, stable disease, and
disease regression were observed in seven patients, two patients, and one patient,
respectively. Six (60%) patients had increased NAS on second biopsy, and two were
lean NASH patients. The only patient with an improvement in NAS had achieved body
weight reduction (13.3%) between paired biopsies. None of the 10 patients
experienced an improvement in fibrosis. Five (50%) patients showed progression of
fibrosis on second biopsy and the annual fibrosis progression rate was 0.32/year.
Two of the five patients who showed progression of fibrosis were of the nonobese
phenotype, whereas three patients were nondiabetic. Conclusion NASH is a
progressive disease in Taiwanese patients. The disease progression should be
further clarified in lean and nondiabetic NASH patients.Copyright © 2018 Wolters
Kluwer Health, Inc. All rights reserved.
sid=OVID:embase&id=pmid:30308578&id=doi:10.1097%2FMEG.0000000000001285&issn=0954-
229&date=2019&title=European+Journal+of+Gastroenterology+and+Hepatology&atitle=Dise
ase+progression+of+nonalcoholic+steatohepatitis+in+Taiwanese+patients
%3A+A+longitudinal+study+of+paired+liver+biopsies&aulast=Lin&pid=%3Cauthor
%3ELin+T.-Y.%3BYeh+M.-L.%3BHuang+C.-F.%3BHuang+C.-I.%3BDai+C.-Y.%3BHsieh+M.-H.
%3BChen+S.-C.%3BHuang+J.-F.%3BYu+M.-L.%3BChuang+W.-L.%3C%2Fauthor%3E%3CAN
<63>
Accession Number
632136775
Title
Role of adiponectin, leptin and IGF-1 as circulating biomarkers in non-alcoholic
fatty liver disease.
Source
United European Gastroenterology Journal. Conference: 27th United European
Gastroenterology Week, UEG. Barcelona Spain. 7(8 Supplement) (pp 197), 2019. Date
Author
Marques V.; Afonso M.B.; Baur N.; Santos-Laso A.; Jimenez-Aguero R.; Eizaguirre
E.; Bujanda L.; Pareja M.J.; Cortez-Pinto H.; Banales J.M.; Castro R.; Normann A.;
Rodrigues C.M.P.
Institution
(Marques, Rodrigues) iMed. ULisboa-Faculdade de Farmacia, Universidade de Lisboa,
Lisboa, Portugal
(Afonso) Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy,
Universidade de Lisboa, Lisbon, Biochemistry and Human biology, Lisbon, Portugal
(Baur, Normann) Mediagnost GmbH, Reutlingen, Germany
(Santos-Laso, Jimenez-Aguero, Bujanda) Biodonostia Institute-Donostia University
Hospital, San Sebastian, Spain
(Eizaguirre) Donostia University Hospital, San Sebastian, Spain
(Pareja) Hospital Juan Ramon Jimenez, Huelva, Spain
(Cortez-Pinto) Faculdade de Medicina de Lisboa, Centro Hospitalar Lisboa Norte,
HSM, Laboratorio de Nutricao, Departamento de Gastroenterologia, Lisboa, Portugal
(Banales) Biodonostia HR-Donostia University Hospital, Liver and Gastrointestinal
Diseases, Bilbao, Spain
(Castro) University of Lisbon Faculty of Pharmacy, iMed.ULisboa and Dep.
Biochemistry and Human Biology, Lisbon, Portugal
Publisher
Subject Headings
adult
cohort analysis
comorbidity
conference abstract
controlled study
diagnosis
diagnostic test accuracy study
disease control
disease free survival
enzyme linked immunosorbent assay
female
fibrosis
gene expression
genotype
*histology
histopathology
hormone determination
human
human tissue
male
obese patient
obesity
protein blood level
protein expression
*protein function
validation process
*adiponectin
*biological marker
endogenous compound
hormone
*leptin
*somatomedin C
triacylglycerol
Drug Index Terms
*adiponectin; *biological marker; endogenous compound; hormone; *leptin;
*somatomedin C; triacylglycerol
Other Index Terms
adult; alanine aminotransferase blood level; cohort analysis; comorbidity;
conference abstract; controlled study; diagnosis; diagnostic test accuracy study;
disease control; disease free survival; enzyme linked immunosorbent assay; female;
fibrosis; gene expression; genotype; *histology; histopathology; hormone
determination; human; human tissue; major clinical study; male; *nonalcoholic
steatohepatitis; obese patient; obesity; protein blood level; protein expression;
*protein function; triacylglycerol blood level; validation process
Abstract
Introduction: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of
conditions from the benign hepatic steatosis to non-alcoholic steatohepatitis
(NASH), which may progress to liver cirrhosis and/or hepatocellular carcinoma. The
gold standard method to distinguish steatosis from NASH is liver biopsy. However,
this is an invasive procedure with risk of complications, which provides a two-
dimensional estimation of a particular biopsy, and is subjected to individual
evaluation by a pathologist. All these limitations prompt the need to discover and
validate new accurate diagnostic biomarkers. Aims & Methods: Here, we aimed to
assess the performance of circulating levels of adiponectin, leptin and insulin-
like growth factor-I (IGF-1) as potential non-invasive biomarkers in NAFLD. Serum
levels of adiponectin, leptin and IGF-1 were evaluated in discovery (n = 59) and
validation (n = 145) cohorts of morbidly obese patients, with clinical and biopsy-
proven diagnosis of NAFLD, using specific enzyme-linked immunosorbent assays.
Hormone levels were correlated with histology findings, clinical parameters,
presence of comorbidities and PNPLA3 genotype. Sera of disease-free individuals,
lean and obese, were also analyzed in both cohorts (n = 20 and n = 32, validation
and discovery cohorts, respectively). Result(s): The results showed that in the
discovery cohort, adiponectin was significantly lower in patients with NASH
compared to steatosis (p < 0.05) or healthy individuals (p < 0.01), and the area
under the receiveroperating characteristic (AUROC) was 0.79 (95% CI = 0.62-0.96; p
< 0.01). The same trend was observed in the validation cohort. Further adiponectin
decreased with histologic severity of steatosis (p < 0.005), inflammation and
fibrosis (p < 0.05), and showed an inverse correlation with serum alanine
aminotransferase (ALT) and triglycerides (p = 0.0023 and p = 0.0055, respectively),
supporting a role for this hormone in NAFLD pathophysiology. In both cohorts,
leptin levels were significantly increased in patients with steatosis or NASH when
compared to healthy lean controls (p < 0.005 and p <0.0001), showing an AUROC of ~
0.9 (p < 0.05 and p < 0.0001 for discovery and validation cohorts, respectively).
Circulating leptin levels were similar between lean and obese controls, suggesting
that obesity is not a confounding factor. Finally, although IGF-I concentrations
were significantly diminished in patients with steatosis or NASH, compared with
controls (p < 0.05) in the discovery cohort, IGF-1 levels were similar between
control individuals and patients with NAFLD in the validation cohort. Strikingly,
IGF-1 levels were significantly lower in more severe fibrosis (p < 0.005) in the
validation cohort, with an AUROC value of 0.71 (95% CI = 0.6-0.82; p < 0.01).
Conclusion(s): In conclusion, these hormones are potentially valuable tools for
non-invasive stratification of patients with NAFLD. In particular, leptin might
discriminate the presence of NAFLD, while IGF-1 could be a biomarker of advanced
fibrosis. Further studies should analyze these hormones in a lean NAFLD control
group and the performance of multivariate analysis to assess the impact of
confounding factors and the potential of combined biomarker parameters.
6414&isbn=&volume=7&issue=8+Supplement&spage=197&pages=197&date=2019&title=United+E
uropean+Gastroenterology+Journal&atitle=Role+of+adiponectin%2C+leptin+and+IGF-
1+as+circulating+biomarkers+in+non-
alcoholic+fatty+liver+disease&aulast=Marques&pid=%3Cauthor%3EMarques+V.
%3BAfonso+M.B.%3BBaur+N.%3BSantos-Laso+A.%3BJimenez-Aguero+R.%3BEizaguirre+E.
%3BBujanda+L.%3BPareja+M.J.%3BCortez-Pinto+H.%3BBanales+J.M.%3BCastro+R.
%3BNormann+A.%3BRodrigues+C.M.P.%3C%2Fauthor%3E%3CAN%3E632136775%3C%2FAN%3E%3CDT
<64>
Accession Number
631815659
Title
High risk of fatty liver disease amplifies the alanine transaminase-lowering
effect of a HSD17B13 variant.
Source
Hepatology v70 suppl.1 2019. Conference: 70th Annual Meeting of the American
Association for the Study of Liver Diseases. Boston, MA United States.
70(Supplement 1) (pp 1148A-1149A), 2019. Date of Publication: October 2019.
Author
Gellert-Kristensen H.; Nordestgaard B.; Tybjaerg-Hansen A.; Stender S.
Institution
(Gellert-Kristensen, Nordestgaard, Tybjaerg-Hansen) University of Copenhagen
(Gellert-Kristensen, Tybjaerg-Hansen, Stender) Clinical Biochemistry, Copenhagen
University Hospital
(Nordestgaard) Clinical Biochemistry, Herlev Hospital
Publisher
Subject Headings
adult
alcohol consumption
cancer patient
conference abstract
controlled study
*fatty liver
female
gene amplification
gene expression
gene frequency
genetic association
genetic risk
heavy drinker
homozygote
human
human tissue
liver cirrhosis
male
mortality
non-drinker
obesity
protein blood level
protein expression
*protein function
risk factor
*alanine aminotransferase
endogenous compound
Drug Index Terms
*alanine aminotransferase; endogenous compound
Other Index Terms
adult; alanine aminotransferase blood level; alcohol consumption; cancer patient;
conference abstract; controlled study; *fatty liver; female; gene amplification;
gene expression; gene frequency; genetic association; genetic risk; genetic
susceptibility; heavy drinker; homozygote; human; human tissue; liver cell
carcinoma; liver cirrhosis; major clinical study; male; mortality; non-drinker;
obesity; protein blood level; protein expression; *protein function; risk factor;
Abstract
Background: A common loss-of-function variant in HSD17B13 (rs72613567:TA) was
recently found to protect from chronic liver disease. Whether the variant confers
protection from specific risk factors for liver disease is unclear Methods: We
tested the association of rs72613567 with plasma levels of alanine transaminase
(ALT) and clinical liver disease and mortality in 111,612 individuals from the
Danish general population, including 497 with cirrhosis and 113 with hepatocellular
carcinoma Results: HSD17B13 rs72613567:TA was associated with stepwise lower levels
of plasma ALT of up to 1 3 U/L in TA/TA homozygotes versus T/T homozygotes For each
TA-allele, the risk of cirrhosis and hepatocellular carcinoma was reduced by 15%
and 28%, respectively In prospective analyses, the TA-allele was associated with up
to 33% lower rates of liver-related mortality in the general population, and with
up to 49% reduced liverrelated mortality in patients with cirrhosis The ALT-
lowering effect of rs72613567:TA was amplified by increasing adiposity, alcohol
consumption, and genetic risk of fatty liver disease The TA-allele was associated
with only marginally lower ALT in lean nondrinkers with low genetic risk of hepatic
steatosis In contrast, compared to T/T homozygotes, TA/TA homozygotes had 12% to
carrying three or four steatogenic alleles in PNPLA3 and TM6SF2 Conclusion(s): High
risk of fatty liver disease amplifies the ALTlowering effect of HSD17B13
rs72613567:TA in the Danish general population.
3350&isbn=&volume=70&issue=Supplement+1&spage=1148A&pages=1148A-
1149A&date=2019&title=Hepatology+v70+suppl.1+2019&atitle=High+risk+of+fatty+liver+d
isease+amplifies+the+alanine+transaminase-
lowering+effect+of+a+HSD17B13+variant&aulast=Gellert-Kristensen&pid=%3Cauthor
%3EGellert-Kristensen+H.%3BNordestgaard+B.%3BTybjaerg-Hansen+A.%3BStender+S.%3C
<65>
Accession Number
631813871
Title
The combined effect of alcohol and obesity on risk of liver disease: A systematic
review and metaanalysis.
Source
Hepatology v70 suppl.1 2019. Conference: 70th Annual Meeting of the American
Association for the Study of Liver Diseases. Boston, MA United States.
70(Supplement 1) (pp 753A), 2019. Date of Publication: October 2019.
Author
Glyn-Owen K.; Bohning D.; Parkes J.; Roderick P.; Buchanan R.
Institution
(Glyn-Owen) NIHR Clahrc Wessex
(Glyn-Owen, Parkes, Roderick) Primary Care and Population Sciences, University of
Southampton
(Bohning) Southampton Statistical Sciences Research Institute, University of
Southampton
(Buchanan) University of Southampton
Publisher
Subject Headings
adult
adverse drug reaction
alcohol consumption
body mass
cancer model
cancer patient
cohort analysis
conference abstract
controlled study
drinking
English (language)
Europe
female
follow up
human
lifestyle
liver cirrhosis
loglinear model
male
meta analysis
morbidity
mortality
*obese patient
*obesity
remission
risk assessment
risk factor
systematic review
*alcohol
Drug Index Terms
*alcohol
Other Index Terms
adult; adverse drug reaction; alcohol consumption; body mass; cancer model;
cancer patient; cohort analysis; conference abstract; controlled study; drinking;
English (language); Europe; female; follow up; human; lifestyle; liver cell
carcinoma; liver cirrhosis; loglinear model; male; meta analysis; morbidity;
mortality; *nonalcoholic fatty liver; *obese patient; *obesity; quantitative
analysis; remission; risk assessment; risk factor; systematic review
Abstract
Background: Liver disease caused by alcohol and obesity is preventable by risk
factor modification. Evidence from individual studies on risk in patients who have
both risk factors is inconsistent. We performed a systematic review and
metaanalysis to quantify the risk of liver disease associated with combinations of
BMI and alcohol consumption Methods: The full study protocol is registered with
PROSPERO (CRD42016046508). Inclusion criteria were: English language publications
in peer-reviewed journals; adults from general population cohorts without pre-
existing liver disease; BMI and alcohol quantifiably measured; follow-up at least
10 years duration Outcomes were incident morbidity/mortality from cirrhosis and/or
hepatocellular carcinoma A onestage meta-analysis was performed on original count
data, using a Poisson regression log-linear model The log-linear model has the
property that joint effects are multiplicative Reference categories were normal
weight (BMI<25) and alcohol consumption above zero but within UK limits (<112 g/wk)
Results: The search identified 2589 studies. 50 underwent full text review Eight
cohorts (Two from the USA, six from Europe) were included in the meta-analysis,
totalling 1,029,962 participants There was no interaction between alcohol and
obesity in the model Risks of liver disease in those with both increased BMI and
alcohol consumption were significantly increased and were multiplicative, as per
the properties of the log-linear model (figure 1). Compared to normal weight
participants drinking <112 g/wk (UK recommended limit), the relative risk of liver
disease in those who were overweight and drinking above limits was 3 60 (95%CI 3
22-4 02) and the relative risk in those who were obese and drinking above limits
was 5 84 (95%CI 5 09-6 70) Conclusion(s): Overweight and obese patients drinking
>112 g/wk are at significantly increased risk of liver disease. This risk should
inform lifestyle advice given to patients and risk stratification by healthcare
professionals. Alcohol thresholds imposed in NAFLD criteria and pathways may mean
that patients with both increased BMI and alcohol risk factors, at risk of Both
Alcohol and Fatty Liver Disease (BAFLD), are not receiving appropriate risk
assessment or clinical care The current guidelines for alcohol consumption may not
be appropriate for obese patients (Figure Presented).
3350&isbn=&volume=70&issue=Supplement+1&spage=753A&pages=753A&date=2019&title=Hepat
ology+v70+suppl.1+2019&atitle=The+combined+effect+of+alcohol+and+obesity+on+risk+of
+liver+disease%3A+A+systematic+review+and+metaanalysis&aulast=Glyn-Owen&pid=
%3Cauthor%3EGlyn-Owen+K.%3BBohning+D.%3BParkes+J.%3BRoderick+P.%3BBuchanan+R.%3C
<66>
Accession Number
2002166112
Title
A diet-induced lean non-alcoholic steatohepatitis-associated hepatocellular
carcinoma mouse model.
Source
Journal of Hepatology. Conference: The International Liver Congress 2019. Vienna
Austria. 70(1) (pp e362-e363), 2019. Date of Publication: April 2019.
Author
Farazi P.; Karanjit S.; Keuter E.; Liu D.; Talmon G.
Institution
(Farazi, Karanjit, Keuter, Liu) University of Nebraska Medical Center,
Epidemiology, Omaha, United States
(Talmon) University of Nebraska Medical Center, Pathology and Microbiology,
Omaha, United States
Publisher
Elsevier B.V.
Subject Headings
adult
animal experiment
animal model
animal tissue
aspartate aminotransferase level
cancer patient
cancer staging
*cholesterol diet
choline deficiency
controlled study
diabetic obesity
drug toxicity
female
fibrosis
glucose level
glucose tolerance test
histopathology
lipid liver level
liver cirrhosis
liver histology
liver injury
liver tissue
low fat diet
male
mouse
*mouse model
nodulation
nonhuman
obesity
penetrance
cholesterol
choline
liver enzyme
sucrose
triacylglycerol
conference abstract
Candidate Terms
Drug Index Terms
cholesterol; choline; liver enzyme; sucrose; triacylglycerol
Other Index Terms
adult; animal experiment; animal model; animal tissue; aspartate aminotransferase
level; cancer patient; cancer staging; cholesterol blood level; *cholesterol diet;
choline deficiency; controlled study; diabetic obesity; drug toxicity; female;
fibrosis; glucose level; glucose tolerance test; histopathology; lipid liver level;
*liver cell carcinoma; liver cirrhosis; liver histology; liver injury; liver
tissue; low fat diet; male; mouse; *mouse model; nodulation; *nonalcoholic
steatohepatitis; nonhuman; obesity; penetrance; triacylglycerol level
Abstract
Background and aims: Non-alcoholic fatty liver disease (NAFLD) has 24% prevalence
globally. Its progressive form (non-alcoholic steatohepatitis; NASH) can lead to
hepatocellular carcinoma (HCC) development. Interestingly, NAFLD can develop in the
absence of obesity and diabetes, with a prevalence of 7% in lean individuals in the
US and 25-30% in some Asian countries as a result of a diet high in
fructose/fat/cholesterol and genetic predisposition affecting lipid export from the
liver. Currently, there is limited understanding of lean NAFLD/NASH HCC
pathogenesis, necessitating the development of mouse models for this disease. The
aim of this work is to develop a diet-induced lean NASH-HCC mouse model. Method(s):
Thirty-five mice were fed a choline deficient, high trans-fat, sucrose, cholesterol
(CD-HFSC) diet and fifteen mice were fed an isocaloric control low fat diet
starting at 4 weeks of age. Choline deficiency is associated with triglyceride
accumulation in the liver similar to genetically susceptible human NAFLD patients.
Mice were weighed weekly, plasma liver enzymes and lipids were assessed at 17 and
26 weeks of age and glucose tolerance tests were performed at 8, 20, 32, and
44weeks. Liver tissue was analyzed post mortem to assess nodule development and
liver histology in order to determine the development of NAFLD, NASH, fibrosis and
HCC. Result(s): Mice fed the CD-HFSC diet developed HCC as early as 46 weeks of age
with high penetrance (60.7%) at 56weeks in the absence of obesity. 92.9% of these
mice developed hyperplastic nodules and 89.3% had dysplastic nodules. 100% of the
mice fed the CD-HFSC diet developed NASH and 51.8% had fibrosis stage 2-3. Mice fed
the CDHFSC diet experienced liver damage as evidenced by the significantly higher
plasma ALT and AST levels (p < 0.05). Mice fed the CD-HFSC diet had lower plasma
cholesterol and triglyceride levels compared to mice fed the control diet,
suggestive of retention of these lipids in the liver. Glucose tolerance was similar
in both diet groups. Interestingly, nodule size at the end point was positively
correlated with higher plasma liver enzyme (AST) and glucose levels at earlier time
points. Conclusion(s): Mice fed a diet deficient in choline and high in trans-fat,
sucrose, and cholesterol experience liver damage and develop lean NASH-HCC in the
absence of cirrhosis by 56weeks of age. This mouse model is expected to aid in
further understanding the pathogenesis of lean NASH-HCC.Copyright © 2019 European
Association for the Study of the Liver
8278&isbn=&volume=70&issue=1&spage=e362&pages=e362-
e363&date=2019&title=Journal+of+Hepatology&atitle=A+diet-induced+lean+non-
alcoholic+steatohepatitis-
associated+hepatocellular+carcinoma+mouse+model&aulast=Farazi&pid=%3Cauthor
%3EFarazi+P.%3BKaranjit+S.%3BKeuter+E.%3BLiu+D.%3BTalmon+G.%3C%2Fauthor%3E%3CAN
<67>
Accession Number
2001820946
Title
A diet-induced lean non-alcoholic steatohepatitis-associated hepatocellular
Source
Journal of Hepatology. Conference: The International Liver Congress. Vienna
Austria. 70(1 Supplement) (pp e362-e363), 2019. Date of Publication: April 2019.
Author
Farazi P.; Karanjit S.; Keuter E.; Liu D.; Talmon G.
Institution
(Farazi, Karanjit, Keuter, Liu) University of Nebraska Medical Center,
Epidemiology, Omaha, United States
(Talmon) University of Nebraska Medical Center, Pathology and Microbiology,
Omaha, United States
Publisher
Elsevier B.V.
Subject Headings
animal experiment
animal model
animal tissue
cancer patient
cancer staging
*cholesterol diet
choline deficiency
controlled study
diabetic obesity
drug toxicity
female
fibrosis
glucose level
histopathology
lipid liver level
liver cirrhosis
liver histology
liver injury
liver tissue
low fat diet
male
mouse
*mouse model
nodulation
nonhuman
obesity
penetrance
cholesterol
choline
liver enzyme
sucrose
triacylglycerol
conference abstract
Candidate Terms
Drug Index Terms
Other Index Terms
animal experiment; animal model; animal tissue; aspartate aminotransferase level;
cancer patient; cancer staging; cholesterol blood level; *cholesterol diet; choline
deficiency; controlled study; diabetic obesity; drug toxicity; female; fibrosis;
glucose level; glucose tolerance test; histopathology; lipid liver level; *liver
cell carcinoma; liver cirrhosis; liver histology; liver injury; liver tissue; low
fat diet; male; mouse; *mouse model; nodulation; *nonalcoholic steatohepatitis;
nonhuman; obesity; penetrance; triacylglycerol level
Abstract
Background and aims: Non-alcoholic fatty liver disease (NAFLD)has 24% prevalence
globally. Its progressive form (non-alcoholic steatohepatitis; NASH)can lead to
hepatocellular carcinoma (HCC)development. Interestingly, NAFLD can develop in the
absence of obesity and diabetes, with a prevalence of 7% in lean individuals in the
US and 25-30% in some Asian countries as a result of a diet high in
fructose/fat/cholesterol and genetic predisposition affecting lipid export from the
liver. Currently, there is limited understanding of lean NAFLD/NASH HCC
pathogenesis, necessitating the development of mouse models for this disease. The
aim of this work is to develop a diet-induced lean NASH-HCC mouse model. Method(s):
Thirty-five mice were fed a choline deficient, high trans-fat, sucrose, cholesterol
(CD-HFSC)diet and fifteen mice were fed an isocaloric control low fat diet starting
at 4 weeks of age. Choline deficiency is associated with triglyceride accumulation
in the liver similar to genetically susceptible human NAFLD patients. Mice were
weighed weekly, plasma liver enzymes and lipids were assessed at 17 and 26 weeks of
age and glucose tolerance tests were performed at 8, 20, 32, and 44 weeks. Liver
tissue was analyzed post mortem to assess nodule development and liver histology in
order to determine the development of NAFLD, NASH, fibrosis and HCC. Result(s):
Mice fed the CD-HFSC diet developed HCC as early as 46 weeks of age with high
penetrance (60.7%)at 56 weeks in the absence of obesity. 92.9% of these mice
developed hyperplastic nodules and 89.3% had dysplastic nodules. 100% of the mice
fed the CD-HFSC diet developed NASH and 51.8% had fibrosis stage 2-3. Mice fed the
CD-HFSC diet experienced liver damage as evidenced by the significantly higher
plasma ALT and AST levels (p < 0.05). Mice fed the CD-HFSC diet had lower plasma
cholesterol and triglyceride levels compared to mice fed the control diet,
suggestive of retention of these lipids in the liver. Glucose tolerance was similar
in both diet groups. Interestingly, nodule size at the end point was positively
correlated with higher plasma liver enzyme (AST)and glucose levels at earlier time
points. Conclusion(s): Mice fed a diet deficient in choline and high in trans-fat,
sucrose, and cholesterol experience liver damage and develop lean NASH-HCC in the
absence of cirrhosis by 56 weeks of age. This mouse model is expected to aid in
further understanding the pathogenesis of lean NASH-HCC.Copyright © 2019 European
Association for the Study of the Liver
sid=OVID:embase&id=pmid:&id=doi:10.1016%2FS0618-8278%252819%252930708-X&issn=0168-
8278&isbn=&volume=70&issue=1+Supplement&spage=e362&pages=e362-
e363&date=2019&title=Journal+of+Hepatology&atitle=A+diet-induced+lean+non-
alcoholic+steatohepatitis-
associated+hepatocellular+carcinoma+mouse+model&aulast=Farazi&pid=%3Cauthor
%3EFarazi+P.%3BKaranjit+S.%3BKeuter+E.%3BLiu+D.%3BTalmon+G.%3C%2Fauthor%3E%3CAN
<68>
Accession Number
626668698
Title
Epidemiology and comorbidity burden of nonalcoholic fatty liver disease (NAFLD)
and nonalcoholic steatohepatitis (NASH) in Japan: A Targeted Literature Review.
Source
Hepatology International. Conference: 28th Annual Conference of Asian Pacific
Association for the Study of the Liver, APASL 2019. Manila Philippines.
13(Supplement 1) (pp S189-S190), 2019. Date of Publication: February 2019.
Author
Eguchi Y.; Wong G.; Lee I.-H.; Akhtar O.; Lopes R.; Sumida Y.
Institution
(Eguchi) Liver Center, Saga University Hospital, Saga, Japan
(Wong, Lee) Gilead Sciences, Inc
(Akhtar, Lopes) Amaris, Ltd
(Sumida) Division of Hepatology and Pancreatology, Department of Internal
Medicine, Aichi Medical University
Publisher
Springer
Subject Headings
adult
body mass
chronic kidney failure
*comorbidity
death
diabetes mellitus
Embase
female
human
hypertension
*Japan
Japanese (citizen)
male
Medline
obese patient
obesity
prevalence
systematic review
conference abstract
Candidate Terms
Other Index Terms
adult; body mass; chronic kidney failure; *comorbidity; death; diabetes mellitus;
Embase; end stage liver disease; female; human; hypertension; *Japan; Japanese
(citizen); male; Medline; *nonalcoholic fatty liver; obese patient; obesity;
prevalence; systematic review
Abstract
Introduction: NAFLD and NASH represent a growing unmet medical need and an
increasingly prevalent cause of end-stage liver disease, HCC and death in Japan.
Method(s): An English and Japanese literature search was conducted in Pubmed,
Embase and ICHUSHI Web, identifying 2792 articles, with 192 included for full-text
review. 66 studies were extracted. Result(s): Prevalence of NAFLD in the Japanese
population rose from the early 1990s (12.6-12.9%) to the early 2000s (24.6-34.7% of
the population). NASH prevalence is estimated to be 1.9-2.7%. NAFLD and NASH are
more common among males than females, however females experience more severe
disease than males. Older patients also demonstrate more severe disease than
younger patients. While obese patients had higher prevalence of NAFLD/NASH, non-
obese individuals (BMI<25) consistently comprised 30 to >50% of NAFLD and NASH
patients. The evidence shows that despite obesity being linked with worse disease
stages, "lean-NASH" also plays an important role in NASH epidemiology. Overall
prevalence of comorbidities such as hypertension (13-86%), diabetes mellitus (33-
71%), and chronic kidney disease (6-21%) was high in the Japanese NAFLD/NASH
population. NAFLD was also a strong predictor of cardiovascular events, with 5% of
NAFLD patients experiencing cardiovascular events over 2 years vs. 1% of healthy
controls. Conclusion(s): NAFLD/NASH is common in the Japanese population and the
prevalence of these conditions has tripled in the last two decades. Furthermore,
these NAFLD/NASH patients have a high comorbidity burden. Early and efficient
identification and safe and effective treatments for NAFLD/NASH patients are
urgently needed.
S190&date=2019&title=Hepatology+International&atitle=Epidemiology+and+comorbidity+b
urden+of+nonalcoholic+fatty+liver+disease+%28NAFLD
%29+and+nonalcoholic+steatohepatitis+%28NASH%29+in+Japan
%3A+A+Targeted+Literature+Review&aulast=Eguchi&pid=%3Cauthor%3EEguchi+Y.%3BWong+G.
%3BLee+I.-H.%3BAkhtar+O.%3BLopes+R.%3BSumida+Y.%3C%2Fauthor%3E%3CAN%3E626668698%3C
<69>
Accession Number
626668042
Title
Comparison of lean versus overweight/obese patients with nonalcoholic fatty liver
disease.
Source
Hepatology International. Conference: 28th Annual Conference of Asian Pacific
Association for the Study of the Liver, APASL 2019. Manila Philippines.
13(Supplement 1) (pp S198), 2019. Date of Publication: February 2019.
Author
Navarroza A.M.C.; Wong S.N.; Guzman M.R.E.; Lim J.Y.
Institution
(Navarroza, Wong, Guzman, Lim) University of Sto., Tomas Hospital
Publisher
Springer
Subject Headings
adult
alcohol consumption
*cancer patient
controlled study
dyslipidemia
female
hepatitis B
human
international normalized ratio
liver cirrhosis
male
*obese patient
*obesity
outpatient
steatosis
ultrasound
underweight
albumin
endogenous compound
liver enzyme
conference abstract
Candidate Terms
Drug Index Terms
alanine aminotransferase; albumin; endogenous compound; high density lipoprotein;
liver enzyme
Other Index Terms
adult; alcohol consumption; *cancer patient; controlled study; dyslipidemia;
female; hepatitis B; human; international normalized ratio; liver cell carcinoma;
liver cirrhosis; major clinical study; male; *metabolic syndrome X; *nonalcoholic
fatty liver; *obese patient; *obesity; outpatient; steatosis; ultrasound;
underweight
Abstract
Compare the clinical and biochemical profiles of normal/underweight (lean) versus
overweight/obese NAFLD patients. Method(s): Consecutive patients diagnosed with
NAFLD on ultrasound in a single outpatient hepatology clinic from February 2007 to
January 2017 were included. Patients with significant alcohol intake, secondary
causes of steatosis, and incomplete data were excluded. Demographics, liver
enzymes, albumin, International normalized ratio (INR), hepatitis and metabolic
biochemical profiles were recorded. Normal alanine aminotransferase (ALT) was
pegged at 24 IU/mL and 19 IU/mL for males and females, respectively. Logistic
regression was used to determine independent predictors. Result(s): We included 663
patients (58.1% male). Most patients were overweight/ obese(74.2%) while 82.1% had
an elevated ALT. Cirrhosis or hepatocellular carcinoma (HCC) were already present
on initial consult in 4.4% and 5.9%, respectively. Concomitant hepatitis B was
equally common in patients with and without cirrhosis (20.7% vs. 17.5%; p = 0.660)
or HCC (17.9% vs. 12.8%, p = 0.415). Compared to Lean NAFLD patients,
overweight/obese patients were more likely to be younger (50.9 + 14.2 vs. 54.6 +
14.2; p = 0.004), and have higher ALT (57 + 52.8 vs. 43.5 + 36.4, p<0.0001) and
INR(1.9 + 9.3 vs. 0.98 + 0.12, p = 0.025). Overweight/obese patients were also more
likely to have DM (49.8% vs. 33.9%; p<0.0001), hypertension (58.3% vs 47.1%, p =
0.007), dyslipidemia (73.6% vs 63.2%; p = 0.011) and metabolic syndrome (63.6% vs
36.8%; p<0.0001), and less likely to be cirrhotic (3.3% vs. 7.6%; p = 0.0265).
Independent factors associated with over weightedness and obesity in NAFLD patients
were younger age (OR = 1.02; 95% Cl = 1.02-1.003; p = 0.014), metabolic syndrome
(OR = 0.358; 95% Cl = 0.5232-0.245; p<0.0001), lower HDL (OR = 1.02; 95% Cl =
1.029-1.005; p = 0.005), and absence of cirrhosis (OR = 2.493; 95% Cl = 5.586-
1.116; p = 0.026). Conclusion(s): Majority of NAFLD patients are overweight/obese,
with elevated ALT, and with a significant proportion (7.8%) already with
cirrhosis/HCC on initial presentation. Overweight/obese NAFLD patients are more
likely to have metabolic derangements and its consequences compared to lean
patients.
0541&isbn=&volume=13&issue=Supplement+1&spage=S198&pages=S198&date=2019&title=Hepat
ology+International&atitle=Comparison+of+lean+versus+overweight
%2Fobese+patients+with+nonalcoholic+fatty+liver+disease&aulast=Navarroza&pid=
%3Cauthor%3ENavarroza+A.M.C.%3BWong+S.N.%3BGuzman+M.R.E.%3BLim+J.Y.%3C%2Fauthor%3E
<70>
Accession Number
622820604
Title
Fatty liver disease in non-obese individuals: Prevalence, pathogenesis and
treatment.
Source
European Journal of Clinical Investigation. Conference: 52nd Annual Scientific
Meeting of the European Society for Clinical Investigation. Barcelona Spain.
48(Supplement 1) (pp 39), 2018. Date of Publication: May 2018.
Author
Krawczyk M.
Institution
(Krawczyk) Department of Medicine Ii, Saarland University Medical Center,
Saarland University, Homburg, Germany
(Krawczyk) Center for Preclinical Research, Department of General, Transplant and
Liver Surgery, Medical University of Warsaw, Warsaw, Poland
Publisher
Subject Headings
adult
cancer patient
controlled study
genetic association
German (citizen)
human
hypertriglyceridemia
insulin resistance
liver cirrhosis
Maryland
North American
*obesity
*prevalence
endogenous compound
conference abstract
Candidate Terms
Drug Index Terms
endogenous compound
Other Index Terms
adult; cancer patient; controlled study; genetic association; genetic
polymorphism; German (citizen); human; hypertriglyceridemia; insulin resistance;
liver cell carcinoma; liver cirrhosis; Maryland; *nonalcoholic fatty liver; North
American; *obesity; *prevalence
Abstract
For many years obesity has been regarded as the main risk factor for the fatty
liver disease (FLD). Non-obese individuals have been, in turn, thought to only
rarely suffer from FLD (Bellentani et al., Liver Int. 2017). Nevertheless, numerous
studies indicate that hepatic steatosis develops also in the absence of obesity or
metabolic disturbances. For example, the prevalence of NAFLD in a large population
of lean North-American individuals was reported at 7.4% (Younossi et al., Medicine
(Baltimore) 2012), some studies estimated that the prevalence of non-obese NAFLD
worldwide might even be as high as 30%. Thus, FLD is prevalent and relevant even in
non-obese individuals. The pathogenesis of fatty liver is multifactorial and
involves both exogenous and inherited determinants. Our most recent analysis of
non-obese and non-diabetic German patients with fatty liver demonstrated that
common prosteatotic variants, especially the PNPLA3 p.I148M polymorphism, are
highly prevalent in these patients (Krawczyk et al., J Huma Genet in press).
Overall, as compared to healthy controls, non-obese patients with FLD seem to
suffer from more insulin resistance and more hypertriglyceridemia even in the
absence of obesity. Of note, alike obese patients, they have increased risk of
developing nonalcoholic steatohepatitis (NASH) as well as cirrhosis and
hepatocellular carcinoma. Here we will present the most recent data concerning the
prevalence and pathogenesis of fatty liver in non-obese. We will also address the
topic of therapy and discuss the involvement of inherited predisposition in the
overall FLD risk in lean individuals.
sid=OVID:embase&id=pmid:&id=doi:10.1111%2Feci.12924&issn=1365-
2362&isbn=&volume=48&issue=Supplement+1&spage=39&pages=39&date=2018&title=European+
Journal+of+Clinical+Investigation&atitle=Fatty+liver+disease+in+non-
obese+individuals%3A+Prevalence%2C+pathogenesis+and+treatment&aulast=Krawczyk&pid=
%3Cauthor%3EKrawczyk+M.%3C%2Fauthor%3E%3CAN%3E622820604%3C%2FAN%3E%3CDT
<71>
Accession Number
621294783
PMID
Title
Clinical relevance of liver histopathology and different histological
classifications of NASH in adults.
Source
Expert Review of Gastroenterology and Hepatology. 12(4) (pp 351-367), 2018. Date
of Publication: 03 Apr 2018.
Author
Nascimbeni F.; Ballestri S.; Machado M.V.; Mantovani A.; Cortez-Pinto H.; Targher
G.; Lonardo A.
Institution
(Nascimbeni, Lonardo) Ospedale Civile di Baggiovara, Azienda Ospedaliero-
Universitaria, Modena, Italy
(Nascimbeni) Department of Biomedical, Metabolic and Neural Sciences, University
of Modena and Reggio Emilia, Modena, Italy
(Ballestri) Azienda USL, Pavullo Hospital, Modena, Italy
(Machado, Cortez-Pinto) Departamento de Gastrenterologia e Hepatologia, Centro
Hospitalar Lisboa Norte, Laboratorio de Nutricao, Faculdade de Medicina de Lisboa,
Lisboa, Portugal
(Mantovani, Targher) Division of Endocrinology, Diabetes and Metabolism,
Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata
of Verona, Verona, Italy
Publisher
Taylor and Francis Ltd (E-mail: [email protected])
Subject Headings
adult
algorithm
clinical feature
disease activity
disease association
*disease classification
disease severity
ethnic group
genetic disorder
high risk patient
*histopathology
human
lean body weight
liver biopsy
liver fibrosis/dt [Drug Therapy]
non invasive measurement
*nonalcoholic fatty liver/su [Surgery]
obesity
prediction
prognosis
review
risk assessment
scoring system
alpha tocopherol/dt [Drug Therapy]
obeticholic acid/dt [Drug Therapy]
pentoxifylline/dt [Drug Therapy]
pioglitazone/dt [Drug Therapy]
NAFLD Activity Score
steatosis activity and fibrosis score
Candidate Terms
NAFLD activity score [other term]
Steatosis Activity and Fibrosis score [other term]
Drug Index Terms
alpha tocopherol / drug therapy; obeticholic acid / drug therapy;
pentoxifylline / drug therapy; pioglitazone / drug therapy
Other Index Terms
adult; algorithm; clinical feature; disease activity; disease association;
*disease classification; disease severity; ethnic group; genetic disorder; high
risk patient; *histopathology; human; lean body weight; liver biopsy; liver
fibrosis / drug therapy; liver transplantation; non insulin dependent diabetes
mellitus; non invasive measurement; *nonalcoholic fatty liver / *diagnosis /
*surgery; obesity; prediction; prognosis; Review; risk assessment; scoring system
Abstract
Introduction: Nonalcoholic fatty liver disease (NAFLD) encompasses simple
steatosis and steatohepatitis (NASH) with or without fibrosis/cirrhosis and
hepatocellular carcinoma. NAFLD occurs epidemically in most areas of the world,
contributes to cardiovascular events and liver-related mortality and therefore
exacts a major economic toll. Areas covered: Here we summarize what clinicians
should know about NAFLD histopathology in adults. We report on the individual
histological features and scoring systems of NAFLD: the NAFLD activity score (NAS)
introduced by the NASH-Clinical Research Network, the 'Fatty Liver Inhibition of
Progression' algorithm and Steatosis, Activity, and Fibrosis (SAF) score. Pros and
cons of histological classifications in NASH are discussed. Special emphasis is
given to liver histopathology in some high-risk patient groups, such as those with
severe obesity and type 2 diabetes. Moreover, we also examine the relationship
between liver histopathology and clinical features, and the impact of liver
histopathology on the long-term prognosis of NAFLD. Finally, we propose an
integrated diagnostic approach which utilizes both non-invasive tools and liver
biopsy in those individual patients with suspected NAFLD. Expert commentary: Based
on expert opinions, we conclude with a research agenda on NAFLD which focuses on
the most burning topics to be addressed over the next five years.Copyright © 2017
Informa UK Limited, trading as Taylor & Francis Group.
sid=OVID:embase&id=pmid:29224471&id=doi:10.1080%2F17474124.2018.1415756&issn=1747-
367&date=2018&title=Expert+Review+of+Gastroenterology+and+Hepatology&atitle=Clinica
l+relevance+of+liver+histopathology+and+different+histological+classifications+of+N
ASH+in+adults&aulast=Nascimbeni&pid=%3Cauthor%3ENascimbeni+F.%3BBallestri+S.
%3BMachado+M.V.%3BMantovani+A.%3BCortez-Pinto+H.%3BTargher+G.%3BLonardo+A.%3C
%2Fauthor%3E%3CAN%3E621294783%3C%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<72>
Accession Number
623526617
PMID
Title
Personalized therapy when tackling nonalcoholic fatty liver disease: a focus on
sex, genes, and drugs.
Source
Expert Opinion on Drug Metabolism and Toxicology. 14(8) (pp 831-841), 2018. Date
of Publication: 03 Aug 2018.
Author
Skubic C.; Drakulic Z.; Rozman D.
Institution
(Skubic, Drakulic, Rozman) Centre for Functional Genomic and Biochips, Institute
of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Publisher
Taylor and Francis Ltd (E-mail: [email protected])
Subject Headings
body fat
disease course
DNA methylation
drug metabolism
*genetic difference
hormone substitution
human
lipid storage
metabolic capacity
*nonalcoholic fatty liver/th [Therapy]
nonhuman
pathogenesis
*personalized medicine
pharmacogenomics
prevalence
review
*sex difference
adipocytokine/ec [Endogenous Compound]
antioxidant/dt [Drug Therapy]
estrogen/ec [Endogenous Compound]
estrogen receptor/ec [Endogenous Compound]
growth hormone/dt [Drug Therapy]
growth hormone/ec [Endogenous Compound]
hydroxymethylglutaryl coenzyme A reductase inhibitor/dt [Drug Therapy]
tamoxifen/dt [Drug Therapy]
testosterone/ec [Endogenous Compound]
untranslated RNA/ec [Endogenous Compound]
Drug Index Terms
adipocytokine / endogenous compound; alpha tocopherol / drug therapy; antioxidant
/ drug therapy; estrogen / endogenous compound; estrogen receptor / endogenous
compound; growth hormone / drug therapy / endogenous compound;
hydroxymethylglutaryl coenzyme A reductase inhibitor / drug therapy; pioglitazone /
drug therapy; tamoxifen / drug therapy; testosterone / endogenous compound;
untranslated RNA / endogenous compound
Other Index Terms
body fat; disease course; DNA methylation; drug metabolism; *genetic difference;
hormone substitution; human; lifestyle modification; lipid storage; metabolic
capacity; *nonalcoholic fatty liver / *diagnosis / *drug therapy / *epidemiology /
*etiology / *therapy; nonhuman; pathogenesis; *personalized medicine;
pharmacogenomics; prevalence; Review; *sex difference; single nucleotide
polymorphism
Abstract
Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver
disease in the world. It describes a term for a group of hepatic diseases including
steatosis, fibrosis, and cirrhosis that can finally lead to hepatocellular
carcinoma. There are many factors influencing NAFLD initiation and progression,
such as obesity, dyslipidemia, insulin resistance, genetic factors, and hormonal
changes. However, there is also lean-NAFLD which is not associated with obesity.
NAFLD is considered to be a sexually dimorphic disease. In most cases, men have a
higher prevalence for the disease compared to premenopausal women. Areas covered:
In this review, we first summarize the NAFLD disease epidemiology, pathology, and
diagnosis. We describe NAFLD progression with the focus on sexual and genetic
differences for disease development and pharmacological treatment. Personalized
treatment for multifactorial NAFLD is discussed in consideration of different
factors, including genetics, gender and sex. Expert opinion: The livers of female
and male NAFLD patients have different metabolic capacities which influence the
metabolism of all drugs applied to such patients. This aspect is not yet
sufficiently taken into account. The liver computational models might quicken the
pace toward assessing personalized disease progression and treatment
options.Copyright © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis
Group.
sid=OVID:embase&id=pmid:29969922&id=doi:10.1080%2F17425255.2018.1492552&issn=1742-
841&date=2018&title=Expert+Opinion+on+Drug+Metabolism+and+Toxicology&atitle=Persona
lized+therapy+when+tackling+nonalcoholic+fatty+liver+disease%3A+a+focus+on+sex
%2C+genes%2C+and+drugs&aulast=Skubic&pid=%3Cauthor%3ESkubic+C.%3BDrakulic+Z.
%3BRozman+D.%3C%2Fauthor%3E%3CAN%3E623526617%3C%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<73>
Accession Number
624566513
Title
Clinical characteristics and long-term outcomes of lean caucasian patients with
non-alcoholic fatty liver disease. A longitudinal international study.
Source
Hepatology. Conference: 69th Annual Meeting of the American Association for the
Study of Liver Diseases, AASLD 2018. San Francisco, CA United States. 68(Supplement
1) (pp 1294A-1295A), 2018. Date of Publication: October 2018.
Author
Younes R.; Govaere O.; Petta S.; Miele L.; Fracanzani A.L.; Rosso C.; Liguori A.;
Francione P.; Eslam M.; Valenti L.; George J.; Anstee Q.M.; Bugianesi E.
Institution
(Younes, Rosso, Bugianesi) Department of Medical Sciences, University of Turin,
Turin, Italy
(Govaere, Anstee) Institute of Cellular Medicine, Newcastle University, Newcastle
upon Tyne, United Kingdom
(Petta) Department of Gastroenterology and Hepatology, DI. Bi.M.I.S University of
Palermo, Rome, Italy
(Miele, Liguori) Area Gastroenterologia Ed Oncologia medica. Fondazione
Policlinico Univ. a. Gemelli Irccs, Universita Cattolica Del Sacro Cuore, Rome,
Italy
(Fracanzani, Francione, Valenti) Department of Pathophysiology and
Transplantation, Ca' Granda Irccs Foundation, Policlinico Hospital, University of
Milan
(Eslam, George) Storr Liver Centre, Westmead Institute for Medical Research,
University of Sydney
Publisher
Subject Headings
adult
advanced cancer
Australia
body mass
*cancer patient
cancer survival
*Caucasian
*clinical feature
clinician
cohort analysis
controlled study
death
diabetes mellitus
dyslipidemia
female
fibrosis
follow up
gender
gene expression
genetic association
histopathology
human
human tissue
Italy
liver biopsy
longitudinal study
male
obese patient
obesity
prevalence
protein expression
survival rate
United Kingdom
endogenous compound
insulin
conference abstract
Candidate Terms
Drug Index Terms
endogenous compound; insulin
Other Index Terms
adult; advanced cancer; Australia; body mass; *cancer patient; cancer survival;
*Caucasian; *clinical feature; clinician; cohort analysis; controlled study; death;
decompensated liver cirrhosis; diabetes mellitus; dyslipidemia; female; fibrosis;
follow up; gender; gene expression; genetic association; histopathology; human;
human tissue; Italy; liver biopsy; liver cell carcinoma; longitudinal study; major
clinical study; male; metabolic syndrome X; *nonalcoholic fatty liver; obese
patient; obesity; prevalence; protein expression; survival rate; United Kingdom
Abstract
Background: NAFLD is commonly associated with obesity. Several studies reported a
"lean" phenotype, with controversial clinical characteristics and no long-term
longitudinal studies available, especially in Western countries. We aimed at
evaluating clinical and histological features in addition to long-term outcomes of
lean patients with NAFLD in an international Caucasian cohort. Method(s): 1186
Caucasian patients underwent a liver biopsy for clinical suspicion of nonalcoholic
fatty liver disease in centres in Italy (Turin, Milan, Rome, Palermo), Australia
(Sydney) and the United Kingdom (Newcastle). Clinical and biochemical data were
collected at the time of biopsy. Patients have then undertaken regular visits for
routine care and clinical events were recorded by clinicians. Result(s): Lean
patients (BMI < 25) represented 18.4% of the cohort (N=218) and were mostly of
Italian origin (N=205, 94%). Compared to obese patients, they were younger, with a
lower prevalence of diabetes (8.8% vs 34.3%, p<0.001) hypertension (25.8% vs 45.3%,
p<0.001) dyslipidaemia (44.2% vs 58.7%, p<0.001), lower levels of insulin (mean
11.9 vs 20.9, p<0.001) and predominantly of male gender. Although lean patients had
less severe histological disease, 52% had NASH and 12% exhibited advanced fibrosis.
No difference in PNPLA3 C>G polymorphism was detected between the two groups. After
a median follow-up of 90 months, both liver and non-liver related events had a
significant higher prevalence in the obese group. Nonetheless, a subgroup of lean
patients progressed to decompensated cirrhosis with 5% (n=10) developing liver
decompensation and one patient developing hepatocellular carcinoma. At multivariate
analysis, diabetes was an independent predictor of progression, determining a
higher risk in lean than in obese individuals (OR 5.8 vs 3.4). Despite a higher
number of deaths in obese patients, survival curves did not show a better outcome
in the lean group, with no significant difference between the two groups' survival
(Log-Rank-Mantel Cox, p=0.063). Conclusion(s): In a Western Caucasian cohort, NAFLD
patients who are lean represent a specific group of young individuals,
predominantly male and of Mediterranean origins, with less severe features of
metabolic syndrome and generally milder histological activity. Nevertheless, in
these patients NAFLD can progress to decompensated cirrhosis and hepatocellular
carcinoma, with survival similar to obese NAFLD cases.
1295A&date=2018&title=Hepatology&atitle=Clinical+characteristics+and+long-
term+outcomes+of+lean+caucasian+patients+with+non-alcoholic+fatty+liver+disease.
+A+longitudinal+international+study&aulast=Younes&pid=%3Cauthor%3EYounes+R.
%3BGovaere+O.%3BPetta+S.%3BMiele+L.%3BFracanzani+A.L.%3BRosso+C.%3BLiguori+A.
%3BFrancione+P.%3BEslam+M.%3BValenti+L.%3BGeorge+J.%3BAnstee+Q.M.%3BBugianesi+E.%3C
<74>
Accession Number
624566362
Title
Development of a lean non-alcoholic fatty liver disease-associated hepatocellular
Source
1) (pp 1240A-1241A), 2018. Date of Publication: October 2018.
Author
Karanjit S.; Keuter E.; Liu D.; Talmon G.; Farazi P.
Institution
(Karanjit, Keuter, Liu, Farazi) Epidemiology, University of Nebraska Medical
Center
(Talmon) Pathology/Microbiology, University of Nebraska Medical Center
Publisher
Subject Headings
animal experiment
animal model
animal tissue
body weight
cancer patient
cholesterol diet
controlled study
female
genetic association
histopathology
lipid liver level
liver histology
liver injury
liver tissue
low fat diet
male
mouse
*mouse model
nonhuman
penetrance
vitamin deficiency
cholesterol
choline
liver enzyme
sucrose
triacylglycerol
conference abstract
Candidate Terms
Drug Index Terms
Other Index Terms
animal experiment; animal model; animal tissue; aspartate aminotransferase level;
body weight; cancer patient; cholesterol blood level; cholesterol diet; controlled
study; female; genetic association; genetic polymorphism; glucose tolerance test;
histopathology; lipid liver level; *liver cell carcinoma; liver histology; liver
injury; liver tissue; low fat diet; male; mouse; *mouse model; *nonalcoholic fatty
liver; nonhuman; penetrance; triacylglycerol level; vitamin deficiency
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) shows a global prevalence
of 24% and is predicted to be the leading cause for liver transplantation in the
United States by 2030. Untreated, it can progress to non-alcoholic steatohepatitis
(NASH) and ultimately hepatocellular carcinoma (HCC). While obesity and diabetes
are two of the factors associated with NAFLD, it also develops in their absence
with a prevalence of 7% in lean individuals in the US and 25-30% in some Asian
countries as a result of a diet high in fructose/fat/cholesterol and genetic
predisposition related to genes (e.g. APOB and PNPLA3) involved in lipid export
from the liver. The pathogenesis of lean NAFLD/NASH HCC is poorly understood and
the development of mouse models for this disease is urgently needed. Method(s): To
induce dietrelated lean NAFLD, NASH, and HCC, thirty-five mice were fed a choline
deficient, high trans-fat, sucrose, cholesterol (CDHFSC) diet and fifteen mice were
fed an isocaloric control low fat diet starting at 4 weeks of age. Choline
deficiency results in triglyceride accumulation in the liver similar to human NAFLD
patients with genetic polymorphisms. Mice were weighed weekly, glucose tolerance
tests were performed at 8, 20, 32, and 44 weeks, and plasma liver enzymes and
lipids were measured at 17 and 26 weeks of age. Liver tissue was analyzed post
mortem to assess liver histology and determine the development of NAFLD, NASH, and
HCC. Result(s): Mice fed the CD-HFSC diet were considered to be of normal weight
but developed HCC as early as 46 weeks of age with high penetrance (62.96%) at 56
weeks. 100% of the mice fed the CD-HFSC diet developed NASH, while 53.3% of the
mice fed the control diet only developed NAFLD. Plasma cholesterol and triglyceride
levels were lower in mice fed the CD-HFSC diet compared to the control diet,
suggestive of retention of these lipids in the liver. Plasma ALT and AST levels
were significantly higher in mice fed the CD-HFSC diet, indicating liver damage (P
< 0.05). Glucose tolerance was similar in both diet groups. Conclusion(s): In
summary, a diet deficient in choline and high in trans-fat, sucrose, and
cholesterol is efficient at inducing liver damage, NASH, and HCC in normalweight
mice by 56 weeks of age. This seems to be a good mouse model to further understand
the pathogenesis of lean NAFLD/NASH-HCC.
1241A&date=2018&title=Hepatology&atitle=Development+of+a+lean+non-
alcoholic+fatty+liver+disease-
associated+hepatocellular+carcinoma+mouse+model&aulast=Karanjit&pid=%3Cauthor
%3EKaranjit+S.%3BKeuter+E.%3BLiu+D.%3BTalmon+G.%3BFarazi+P.%3C%2Fauthor%3E%3CAN
<75>
Accession Number
624566109
Title
Totum-63 reduces hepatic steatosis in diet-induced obese mice.
Source
1) (pp 1039A), 2018. Date of Publication: October 2018.
Author
Vluggens A.; Chavanelle V.; Otero Y.; Ripoche-Biache D.; Sirvent P.; Peltier S.
Institution
(Vluggens, Chavanelle, Otero, Ripoche-Biache, Sirvent) Preclinical Research,
Valbiotis
(Peltier) Valbiotis
Publisher
Subject Headings
adult
animal experiment
animal model
body fat
body weight gain
C57BL 6 mouse
cancer staging
catabolism
controlled study
disease course
fibrosis
food intake
France
histopathology
inflammation
lipid liver level
lipid storage
liver cirrhosis
liver failure
liver injury
male
mouse
nonhuman
prevention
signal transduction
software
treatment failure
Western blotting
corn oil
endogenous compound
hormone sensitive lipase
triacylglycerol
triacylglycerol lipase
conference abstract
Candidate Terms
Drug Index Terms
corn oil; endogenous compound; hormone sensitive lipase; triacylglycerol;
triacylglycerol lipase
Other Index Terms
adult; animal experiment; animal model; body fat; body weight gain; C57BL 6
mouse; cancer staging; catabolism; controlled study; *diet induced obesity; disease
course; fibrosis; food intake; France; histopathology; inflammation; lipid liver
level; lipid storage; liver cell carcinoma; liver cirrhosis; liver failure; liver
injury; male; mouse; *nonalcoholic fatty liver; nonhuman; prevention; quantitative
analysis; real time polymerase chain reaction; signal transduction; software;
treatment failure; triacylglycerol level; Western blotting
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic
liver disease reported in current clinical practice. Its prevalence is estimated
ranging from 25% to 45% of adults worldwide, increasing in parallel with that of
obesity and diabetes. More than 10% of NAFLD cases evolve into progressive liver
injuries in the form of nonalcoholic steatohepatitis, which can further lead to
fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. NAFLD is mainly
characterized by abnormal lipid accumulation in hepatocytes, mostly under the form
of triglycerides, which is known as steatosis, associated or not with nonspecific
inflammation. We have developed TOTUM-63, an active principle ingredient candidate
for managing NAFLD. Method(s): To determine whether TOTUM-63 may have beneficial
effects on hepatic steatosis progression, C57BL/6JRj male mice were fed a High-Fat-
Diet (260HFD, Safe, France) with or without supplementation in TOTUM-63 (2,7%) for
16 weeks. A third group was used as control and fed a A03 diet (diet enriched with
3% corn oil, Safe, France). To assess our results, we have generated histological
pictures to quantify the progression of steatosis. Triglyceride amount was
quantified by Red oil staining using ImajeJ software, and alternatively by hepatic
and plasmatic dosages. To understand signaling pathways involved by Totum-63, qPCR
and western blot have been completed. Result(s): Our results show that TOTUM-63
supplementation causes a lower reduction in body weight gain, which could be
explained by a significantly lower body fat mass through the activation of the
pathway hormone-sensitive lipase (HSL)/adipose triglyceride lipase (AGTL), while
lean mass was preserved. TOTUM-63 supplementation also strongly reduces steatosis
by decreasing hepatic triglyceride level (about 43% down, p<0.05). The histological
analysis reveals that Totum-63 supplementation reduces hepatic macrovesicular
steatosis with mild lobular inflammation and cellular ballooning to the stage of
microvesicular steatosis. Moreover, several gene expressions implicated in hepatic
lipid catabolism are upregulated by Totum-63 supplementation and it also regulates
some gene expressions involved in the trafficking of lipids. These effects where
independent of any modification of food intake. Conclusion(s): Thus, Totum-63 is a
promising candidate to prevent hepatic steatosis progression in diet-induced obese
mice. (Figure Presented).
3350&isbn=&volume=68&issue=Supplement+1&spage=1039A&pages=1039A&date=2018&title=Hep
atology&atitle=Totum-63+reduces+hepatic+steatosis+in+diet-
induced+obese+mice&aulast=Vluggens&pid=%3Cauthor%3EVluggens+A.%3BChavanelle+V.
%3BOtero+Y.%3BRipoche-Biache+D.%3BSirvent+P.%3BPeltier+S.%3C%2Fauthor%3E%3CAN
<76>
Accession Number
623769731
PMID
Title
Characteristics of hepatic insulin-sensitive nonalcoholic fatty liver disease.
Source
Hepatology Communications. 1(7) (pp 634-647), 2017. Date of Publication:
September 2017.
Author
Shigiyama F.; Kumashiro N.; Furukawa Y.; Funayama T.; Takeno K.; Wakui N.;
Ikehara T.; Nagai H.; Taka H.; Fujimura T.; Uchino H.; Tamura Y.; Watada H.; Nemoto
T.; Shiraga N.; Sumino Y.; Hirose T.
Institution
(Shigiyama, Kumashiro, Uchino, Hirose) Division of Diabetes, Metabolism, and
Endocrinology, Department of Medicine, Toho University Graduate School of Medicine,
Tokyo, Japan
(Furukawa, Funayama, Takeno, Tamura, Watada) Department of Metabolism and
Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan
(Wakui, Ikehara, Nagai, Sumino) Division of Gastroenterology and Hepatology,
Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan
(Taka) Laboratory of Proteomics and Biomolecular Science, Research Support
Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
(Fujimura) Laboratory of Bioanalytical Chemistry, Tohoku Medical and
Pharmaceutical University, Sendai, Japan
(Tamura, Watada) Sportology Center, Juntendo University Graduate School of
Medicine, Tokyo, Japan
(Nemoto) Department of Surgical Pathology, Toho University Graduate School of
Medicine, Tokyo, Japan
(Shiraga) Department of Radiology, Toho University Graduate School of Medicine,
Tokyo, Japan
Publisher
Subject Headings
adipose tissue
adult
aged
article
blood level
citric acid cycle
clinical article
controlled study
disease marker
disease severity
fat content
female
gene expression
gluconeogenesis
histopathology
human
human tissue
hyperinsulinemic-euglycemic clamp technique
insulin resistance/di [Diagnosis]
*insulin sensitivity
intra-abdominal fat
lifestyle
liver biopsy
male
metabolomics
middle aged
muscle
obesity
priority journal
proton nuclear magnetic resonance
subcutaneous fat
aconitic acid/ec [Endogenous Compound]
adiponectin/ec [Endogenous Compound]
citric acid/ec [Endogenous Compound]
isotope
Drug Index Terms
aconitic acid / endogenous compound; adiponectin / endogenous compound; citric
acid / endogenous compound; fatty acid / endogenous compound; isotope
Other Index Terms
adipose tissue; adult; aged; Article; blood level; citric acid cycle; clinical
article; controlled study; disease marker; disease severity; fat content; female;
gene expression; gluconeogenesis; histopathology; human; human tissue;
hyperinsulinemic-euglycemic clamp technique; insulin resistance / diagnosis;
*insulin sensitivity; intra-abdominal fat; lifestyle; liver biopsy; male;
metabolomics; middle aged; muscle; *nonalcoholic fatty liver / *diagnosis; obesity;
priority journal; proton nuclear magnetic resonance; subcutaneous fat
Abstract
Nonalcoholic fatty liver disease (NAFLD) plays a crucial role in type 2 diabetes
and hepatocellular carcinoma. The major underlying pathogenesis is hepatic insulin
resistance. The aim of the present study was to characterize patients with NAFLD
with paradoxically normal hepatic insulin sensitivity relative to patients with
NAFLD with hepatic insulin resistance. We recruited 26 patients with NAFLD and
divided them into three groups ranked by the level of hepatic insulin sensitivity
(HIS; high-HIS, mid-HIS, low-HIS), as assessed by the hyperinsulinemic-euglycemic
clamp studies using stable isotope. Hepatic insulin sensitivity of the high-HIS
group was identical to that of the non-NAFLD lean control (clamped percent
suppression of endogenous glucose production, 91.1% +/- 5.2% versus 91.0% +/- 8.5%,
respectively) and was significantly higher than that of the low-HIS group (66.6%
+/- 7.5%; P < 0.01). Adiposity (subcutaneous, visceral, intrahepatic, and muscular
lipid content), hepatic histopathology, and expression levels of various genes by
using liver biopsies, muscle, and adipose tissue insulin sensitivity, plasma
metabolites by metabolomics analysis, putative biomarkers, and lifestyles were
assessed and compared between the high-HIS and low-HIS groups. Among these, adipose
tissue insulin sensitivity assessed by clamped percent suppression of free fatty
acid, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle
metabolites, such as citric acid and cis-aconitic acid, were significantly higher
in the high-HIS group compared to the low-HIS group. In contrast, there were no
differences in adiposity, including intrahepatic lipid content assessed by proton
magnetic resonance spectroscopy (28.3% +/- 16.1% versus 20.4% +/- 9.9%,
respectively), hepatic histopathology, other putative biomarkers, and lifestyles.
Conclusion(s): High levels of adipose tissue insulin sensitivity, serum high
molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites are
unique characteristics that define patients with hepatic insulin-sensitive NAFLD
regardless of intrahepatic lipid content. (Hepatology Communications 2017;1:634-
647).Copyright © 2017 The Authors. Hepatology Communications published by Wiley
Periodicals, Inc., on behalf of the American Association for the Study of Liver
Diseases.
sid=OVID:embase&id=pmid:29404483&id=doi:10.1002%2Fhep4.1077&issn=2471-
647&date=2017&title=Hepatology+Communications&atitle=Characteristics+of+hepatic+ins
ulin-sensitive+nonalcoholic+fatty+liver+disease&aulast=Shigiyama&pid=%3Cauthor
%3EShigiyama+F.%3BKumashiro+N.%3BFurukawa+Y.%3BFunayama+T.%3BTakeno+K.%3BWakui+N.
%3BIkehara+T.%3BNagai+H.%3BTaka+H.%3BFujimura+T.%3BUchino+H.%3BTamura+Y.
%3BWatada+H.%3BNemoto+T.%3BShiraga+N.%3BSumino+Y.%3BHirose+T.%3C%2Fauthor%3E%3CAN
<77>
Accession Number
617606636
PMID
Title
New trends on obesity and NAFLD in Asia.
Source
Journal of Hepatology. 67(4) (pp 862-873), 2017. Date of Publication: October
2017.
Author
Fan J.-G.; Kim S.-U.; Wong V.W.-S.
Institution
(Fan) Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital
Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
(Kim) Department of Internal Medicine, Institute of Gastroenterology, Yonsei
University College of Medicine, Seoul, South Korea
(Wong) Department of Medicine and Therapeutics, The Chinese University of Hong
Kong, Hong Kong
(Wong) State Key Laboratory of Digestive Disease, The Chinese University of Hong
Kong, Hong Kong
Publisher
Elsevier B.V.
Subject Headings
Asia
bariatric surgery
chronic hepatitis B
clinical assessment
diet supplementation
epidemiological data
fatty liver
genetics
human
incidence
liver disease
managed care
*obesity/ep [Epidemiology]
pharmaceutical care
phase 3 clinical trial (topic)
prevalence
priority journal
review
risk factor
sarcopenia
sedentary lifestyle
therapy effect
Other Index Terms
Asia; bariatric surgery; chronic hepatitis B; clinical assessment; diet
supplementation; epidemiological data; fatty liver; genetics; human; incidence;
lifestyle modification; liver disease; managed care; meta analysis (topic);
metabolic syndrome X; *nonalcoholic fatty liver; *obesity / *epidemiology;
pharmaceutical care; phase 3 clinical trial (topic); prevalence; priority journal;
Review; risk factor; sarcopenia; sedentary lifestyle; therapy effect
Abstract
Traditionally, obesity and its related diseases have been considered a problem in
Western countries. However, in the past two decades, urbanisation in many Asian
countries has led to a sedentary lifestyle and overnutrition, setting the stage for
the epidemic of obesity. This article reviews the epidemiological trend of obesity
in Asia, with special emphasis on the emerging condition of non-alcoholic fatty
liver disease (NAFLD). Currently, the population prevalence of NAFLD in Asia is
around 25%, like many Western countries. While hepatocellular carcinoma and end-
stage liver disease secondary to NAFLD remain uncommon, a rising trend has emerged.
Around 8-19% of Asians with body mass indexes less than 25 kg/m2 are also found to
have NAFLD, a condition often described as "lean" or "non-obese" NAFLD. Although
this condition is generally less severe than that in more obese patients,
steatohepatitis and fibrotic disease are well recognized. Central adiposity,
insulin resistance and weight gain are major risk factors, and genetic
predisposition, such as the PNPLA3 polymorphism appears to be more important in the
development of NAFLD in the non-obese population. Lifestyle modification remains
the cornerstone of management for obesity and NAFLD, but few patients can achieve
adequate weight reduction and even fewer can maintain the weight in the long run.
While pharmacological agents have entered phase III development for
steatohepatitis, Asian patients are under-represented in most drug trials. Future
studies should define the optimal management of obesity and NAFLD in Asia.Copyright
© 2017 European Association for the Study of the Liver
sid=OVID:embase&id=pmid:28642059&id=doi:10.1016%2Fj.jhep.2017.06.003&issn=0168-
873&date=2017&title=Journal+of+Hepatology&atitle=New+trends+on+obesity+and+NAFLD+in
+Asia&aulast=Fan&pid=%3Cauthor%3EFan+J.-G.%3BKim+S.-U.%3BWong+V.W.-S.%3C%2Fauthor
<78>
Accession Number
612270782
PMID
Title
Nonalcoholic fatty liver disease in Asia: emerging perspectives.
Source
Journal of Gastroenterology. 52(2) (pp 164-174), 2017. Date of Publication: 01
Feb 2017.
Author
Seto W.-K.; Yuen M.-F.
Institution
(Seto, Yuen) Department of Medicine, Queen Mary Hospital, The University of Hong
Kong, Pokfulam Road, Pok Fu Lam, Hong Kong
(Seto, Yuen) State Key Laboratory for Liver Research, The University of Hong
Kong, Pok Fu Lam, Hong Kong
Publisher
Springer Tokyo (E-mail: [email protected])
Subject Headings
age distribution
Asia
clinical feature
disease course
human
prevalence
priority journal
review
risk factor
sex ratio
virus hepatitis
Other Index Terms
age distribution; Asia; clinical feature; disease course; human; *nonalcoholic
fatty liver / *epidemiology; prevalence; priority journal; Review; risk factor; sex
ratio; virus hepatitis
Abstract
As in the West, nonalcoholic fatty liver disease (NAFLD) is the commonest chronic
liver disease in Asia, with a prevalence higher than 40 % in some countries. The
risk factors for NAFLD development are similar to those in Western countries,
including increased body mass index, diabetes, insulin resistance, and metabolic
syndrome. NAFLD in Asians is associated with different extrahepatic manifestations
involving the cardiovascular, gastrointestinal, and renal systems. A considerable
proportion of Asians with NAFLD are described as having "lean" NAFLD. Present in
approximately 20 % of the Asian population, lean NAFLD is closely linked with
insulin resistance, diabetes, and other metabolic complications, but its
association with disease progression to nonalcoholic steatohepatitis and cirrhosis
remains to be defined. There is emerging evidence of the interactions of NAFLD with
hepatitis B virus and hepatitis C virus infection in Asia. Unlike in Western
countries, NAFLD constitutes only a minority of cirrhosis and hepatocellular
carcinoma cases in Asia. Possible explanations are the lower prevalence of obesity
and the overwhelming problem of viral hepatitis in Asia. With aging of the obesity
cohort in Asia, NAFLD-related liver complications are expected to
increase.Copyright © 2016, Japanese Society of Gastroenterology.
174&date=2017&title=Journal+of+Gastroenterology&atitle=Nonalcoholic+fatty+liver+dis
ease+in+Asia%3A+emerging+perspectives&aulast=Seto&pid=%3Cauthor%3ESeto+W.-K.
%3BYuen+M.-F.%3C%2Fauthor%3E%3CAN%3E612270782%3C%2FAN%3E%3CDT%3EReview%3C%2FDT%3E
<79>
Accession Number
621223394
Title
Evolution of body weight parameters up to 3 years after liver transplantation:
The prospective Swiss transplant cohort study.
Source
Journal of Hepatology. Conference: International Liver Congress 2017 - 52nd
Annual Meeting of the European Association for the Study of the Liver. Amsterdam
Netherlands. 66(1 Supplement 1) (pp S197-S198), 2017. Date of Publication: 2017.
Author
Beckmann S.; Dutkowski P.; Nikolic N.; Denhaerynck K.; Binet I.; Koller M.; Boely
E.; De Geest S.
Institution
(Beckmann, Denhaerynck, De Geest) Department Public Health, Institute of Nursing
Science, University of Basel, Basel, Switzerland
(Beckmann) Department of Abdomen-Metabolism, Swaziland
(Dutkowski) Department of Surgery and Transplantation, Switzerland
(Nikolic) Department of Neurosurgery, University Hospital Zurich, Zurich,
Switzerland
(Binet) Nephrologyand Transplantation Medicine, Cantonal Hospital St. Gallen, St.
Gallen, Switzerland
(Koller) Transplantation Immunology and Nephrology, University Hospital Basel,
Basel, Switzerland
(Boely) University Hospital of Geneva, Geneva, Switzerland
(De Geest) Department of Public Health and Primary Care, Academic Center for
Nursing and Midwifery, Leuven, Belgium
Publisher
Elsevier B.V.
Subject Headings
adult
body mass
*body weight change
body weight gain
*cohort analysis
controlled study
female
gender
human
incidence
liquid
*liver transplantation
longitudinal study
male
middle aged
multicenter study
obesity
population
prevalence
*prospective study
recipient
reference value
conference abstract
Candidate Terms
Other Index Terms
adult; body mass; *body weight change; body weight gain; *cohort analysis;
controlled study; end stage liver disease; female; gender; human; incidence;
liquid; liver cell carcinoma; *liver transplantation; longitudinal study; major
clinical study; male; middle aged; multicenter study; nonalcoholic fatty liver;
obesity; population; prevalence; *prospective study; recipient; reference value
Abstract
Background and Aims: Obesity andweight gain are serious concerns after liver
transplantation (LTx), associated with comorbidities such as diabetes mellitus or
de novo nonalcoholic fatty liver disease. The pattern of weight gain however, might
be different based on body mass index (BMI) category or end-stage organ disease.
Investigations on the evolution of body weight parameters have been limited by a
lack of longitudinal studies beyond the first year after LTx; and a detailed
comparison of various bodyweight parameters has not been performed so far. We
examined the evolution of different body weight parameters (BMI, weight change in
kg and % categories) up to 3 years after LTx, using data from the prospective,
nationwide Swiss Transplant Cohort Study. Method(s): Changes in meanweight and BMI
categorywere compared to reference value at 6 months post-LTx to allowa baseline
with "dry" body weight without pre-LTx and immediate post-LTx fluid overload.
Generalized estimating equationwas used to examine the differences of weight change
depending on end-stage liver disease. Result(s): The analysis included 295 adult
liver recipients (65% male, mean age 52.7 +/- 11.3 years), transplanted between May
2008 and May 2012. Based on the reference weight at 6 months, the overall
meanweight gain at 1, 2 and 3 years was 2.1 +/- 5.4 kg, 3.6 +/- 8.2 kg, and 4.8 +/-
10.4 kg, respectively. Those being normal weight and obese at 6 months,
subsequently gained more weight compared to the other BMI subgroups. At 3 years
post-LTx, 57.4% of the recipients gained >5% of their reference body weight. The
prevalence of obesity increased from 5.9% to 18.8% between 6 months and 3 years
post-LTx. Incidence of new onset obesity was 38.1% at 3 years post-LTx. Recipients
with LTx due to nonalcoholic steatohepatitis and alcoholic liver cirrhosis gained
significantly more weight (13.6 +/- 3.8 kg, odds ratio = 6.07, p = 0.010 and 8.4
+/- 10.4 kg, odds ratio = 5.46, p = 0.001, respectively) compared to those with
hepatocellular carcinoma (0.9 +/- 10.9 kg), independent of age, gender and BMI
(Figure 1). Conclusion(s): Compared to international data, our LTx recipients
gained lessweight. Prevalence of obesitywas higher compared to the Swiss general
population. Our results showed important differences in weight gain pattern among
the BMI subgroups that call for preventive measures. Especially normal weight and
obese LTx recipients and those, transplanted for nonalcoholic steatohepatitis and
alcoholic liver cirrhosis should be targeted for weight management interventions
(Figure presented).
0641&isbn=&volume=66&issue=1+Supplement+1&spage=S197&pages=S197-
S198&date=2017&title=Journal+of+Hepatology&atitle=Evolution+of+body+weight+paramete
rs+up+to+3+years+after+liver+transplantation
%3A+The+prospective+Swiss+transplant+cohort+study&aulast=Beckmann&pid=%3Cauthor
%3EBeckmann+S.%3BDutkowski+P.%3BNikolic+N.%3BDenhaerynck+K.%3BBinet+I.%3BKoller+M.
%3BBoely+E.%3BDe+Geest+S.%3C%2Fauthor%3E%3CAN%3E621223394%3C%2FAN%3E%3CDT
<80>
Accession Number
618935529
Title
Hepatocyte notch activation induces liver fibrosis in NASH.
Source
Study of Liver Diseases, AASLD 2017. Washington, DC United States. 66(Supplement 1)
(pp 1047A), 2017. Date of Publication: October 2017.
Author
Zhu C.; Pajvani U.
Institution
(Zhu, Pajvani) Department of Medicine, Columbia University, New York, NY, United
States
Publisher
Subject Headings
adult
animal experiment
animal model
animal tissue
cell activity
Colombia
comorbidity
controlled study
diet
female
gene expression
*hepatic stellate cell
inflammation
*liver fibrosis
liver injury
loss of function mutation
male
mouse
mouse model
nonhuman
Notch signaling
obesity
pathology
plasma
cholesterol
collagen
drinking water
endogenous compound
fructose
Notch receptor
osteopontin
palmitic acid
Drug Index Terms
cholesterol; collagen; drinking water; endogenous compound; fructose; Notch
receptor; osteopontin; palmitic acid
Other Index Terms
adult; animal experiment; animal model; animal tissue; cell activity; Colombia;
comorbidity; controlled study; diet; female; gene expression; *hepatic stellate
cell; inflammation; liver cell carcinoma; *liver fibrosis; liver injury; loss of
function mutation; male; mouse; mouse model; nonalcoholic fatty liver; nonhuman;
Notch signaling; obesity; pathology; plasma
Abstract
Background: Non-Alcoholic Steatohepatitis (NASH) is the fastest growing
complication of obesity, and is associated with comorbidities such as fibrosis and
hepatocellular carcinoma (HCC). However, there are no approved NASH therapeutics-
novel pathways are sought to further our understanding of the pathophysiology of
NASH as well as provide new pharmaceutical targets to assist in our management of
patients. The Notch signaling pathway is an evolutionarily conserved pathway that
determines cell fate during development. We have observed that Notch activity is
present at low levels in normal liver, increases markedly in livers from obese
patients and diet-induced or genetic mouse models of obesity, but is highest in
patients with non-alcoholic steatohepatitis (NASH). These data prompted us to
evaluate whether Notch is causative to NASH pathogenesis, and, given the
pharmacologic accessibility, whether we could repurpose existing Notch therapeutics
to treat NASH. Method(s): We used a dietary "mouse NASH" model which combines
fructose-containing drinking water with a diet rich in palmitate and cholesterol
(hence, FPC diet) that induces profound hepatic steatosis, inflammation and
fibrosis. We coupled this diet to hepatocyte-specific Notch loss-and gain-of-
function mouse models, as well as a well-defined Notch inhibitor DBZ, with
confirmatory work in isolated hepatocytes and hepatic stellate cells (HSCs). The
Columbia University IACUC approved all animal experiments. Result(s): We found
liver Notch activity to be markedly increased in FPC-fed mice, specifically in
hepatocytes, as compared to chow-fed controls. In two different hepatocyte Notch
loss-of-function mouse models, we observed reduced HSC activity and less hepatic
collagen deposition, whereas constitutive hepatocyte Notch activity accelerated
FPC-induced NASH pathologies, increasing plasma ALT and liver fibrosis, and induced
fully penetrant HCC. Intriguingly, Notch-induced fibrosis occurs even in chow-fed
lean mice, in the absence of apparent liver injury, due to increased hepatocyte
Osteopontin (OPN) secretion which is consistent with a strong correlation between
Notch activity in patients with NASH/fibrosis and OPN expression. Finally, in proof
of principle studies, we "treated" FPC-fed mice with DBZ, which ameliorated liver
fibrosis. Conclusion(s): Our results demonstrate that hepatocyte Notch activation
is required for the full development of NASH-associated fibrosis, likely via
induction of Opn. Genetic or pharmacologic inhibition of liver Notch signaling
could prevent and even reverse fibrosis, suggesting that liver-specific Notch
inhibitors may be novel treatments for NASH and associated comorbidities.
3350&isbn=&volume=66&issue=Supplement+1&spage=1047A&pages=1047A&date=2017&title=Hep
atology&atitle=Hepatocyte+notch+activation+induces+liver+fibrosis+in+NASH&aulast=Zh
u&pid=%3Cauthor%3EZhu+C.%3BPajvani+U.%3C%2Fauthor%3E%3CAN%3E618935529%3C%2FAN%3E
<81>
Accession Number
618671640
Title
Lean patients with nonalcoholic fatty liver disease have worse survival rates,
higher frequency of cirrhosis, and decompensation compared to non-lean patients.
Source
Gastroenterology. Conference: Digestive Disease Week 2017, DDW 2017. Chicago, IL
United States. 152(5 Supplement 1) (pp S1201), 2017. Date of Publication: April
2017.
Author
Mansour W.; Young S.; Hoppmann N.A.; Singal A.K.
Publisher
W.B. Saunders
Subject Headings
aged
all cause mortality
body mass
*cancer survival
chi square test
cohort analysis
controlled study
*decompensated liver cirrhosis
diabetes mellitus
diagnosis
dyslipidemia
female
gender
human
hypertension
liver biopsy
male
Model For End Stage Liver Disease Score
*Nonalcoholic Fatty Liver Disease Activity Score
prevalence
prospective study
steatosis
Student t test
*survival rate
survivor
ultrasound
Other Index Terms
aged; all cause mortality; body mass; *cancer survival; chi square test; cohort
analysis; controlled study; *decompensated liver cirrhosis; diabetes mellitus;
diagnosis; dyslipidemia; female; gender; human; hypertension; liver biopsy; liver
cell carcinoma; major clinical study; male; Model For End Stage Liver Disease
Score; *Nonalcoholic Fatty Liver Disease Activity Score; prevalence; prospective
study; steatosis; Student t test; *survival rate; survivor; ultrasound
Abstract
Introduction: Due to the rising incidence of obesity in the United States,
nonalcoholic fatty liver disease (NAFLD) is rapidly growing as an etiology of
cirrhosis and indication for liver transplantation. However, a group of NAFLD
patients are lean (body mass index [BMI] below 25). Data on NAFLD characteristics
and their survival in lean patients are scanty. Method(s): We performed this study
on a cohort of NAFLD patients enrolling in a prospective study at our center.
Diagnosis of NAFLD was based on excluding other causes of liver disease and
presence of steatosis on ultrasound or liver biopsy. Nonalcoholic steatohepatitis
(NASH) was diagnosed based on liver biopsy with NAFLD activity score (NAS) of >4.
NAFLD patients were stratified to lean and non-lean based on BMI cut-off at 25.
Baseline characteristics were compared using t-test for continuous variables and
Chi-square test for categorical variables. Logistic regression model was used for
predictors. Result(s): Of the 1100 NAFLD patients, 68 (6.2%) were lean. The lean
patients had a mean age of 65 and mean BMI of 22, with 10% CAD, 78% cirrhosis, 62%
decompensated, 49% diabetes, 51% dyslipidemia, 56% hypertension, 79% females.
Compared to 1032 non-lean (median BMI 35), lean NAFLD patients (median BMI 22) had
a higher frequency of cirrhosis (78 vs. 66%, P=0.051) anddecompensation of liver
disease (62 vs 51%, P=0.043), P<0.0001. Overall mortality was 12%. higher among
lean patients (26.5 vs. 11%, P<0.0001). Compared to survivors, deceased patients
were more often lean (20 vs. 5%, P=0.0009) and had a higher frequency of cirrhosis
(98 vs. 49%, P<0.0001), hepatocellular carcinoma (HCC) (16 vs. 2%, P<0.0001), and a
higher MELD score (16 vs. 7, P<0.0001). On logistic regression analysis, odds of
mortality were about 3 fold among lean NAFLD patients 2.84 (1.53-5.28), with other
predictors being male gender 1.5 [1.01-2.22] and cirrhosis 33 [8-137].
Discussion(s): Prevalence of lean NAFLD in this cohort is around 6%. Lean NAFLD
patients compared to non-lean patients have a higher frequency of cirrhosis,
decompensation, and worse survival. Studies are suggested to examine mechanisms of
NAFLD in lean patients as basisfor developing strategies to improve outcome of
patients with lean NAFLD.
0012&isbn=&volume=152&issue=5+Supplement+1&spage=S1201&pages=S1201&date=2017&title=
Gastroenterology&atitle=Lean+patients+with+nonalcoholic+fatty+liver+disease+have+wo
rse+survival+rates%2C+higher+frequency+of+cirrhosis
%2C+and+decompensation+compared+to+non-lean+patients&aulast=Mansour&pid=%3Cauthor
%3EMansour+W.%3BYoung+S.%3BHoppmann+N.A.%3BSingal+A.K.%3C%2Fauthor%3E%3CAN
<82>
Accession Number
618564435
Title
High fat diet increases development of hepatocellular carcinoma in glycine N-
methyltransferase deficient mice.
Source
Meeting 2017. Washington, DC United States. 77(13 Supplement 1) (no pagination),
2017. Date of Publication: July 2017.
Author
VanSaun M.N.; Mendonsa A.; Messaggio F.; Nagathihalli N.; Gorden L.
Institution
(VanSaun, Messaggio, Nagathihalli) Univ. of Miami, Miami, FL, United States
(Mendonsa) Seattle Childrens' Research Institute, Seattle, WA, United States
(Gorden) Vanderbilt University, Nashville, TN, United States
Publisher
Subject Headings
animal experiment
animal model
animal tissue
calorie
cancer size
cancer staging
cancer susceptibility
cell proliferation
controlled study
fatty liver
gene expression
hepatomegaly
*lipid diet
liver weight
microenvironment
mouse
murine model
nonhuman
nuclear magnetic resonance imaging
obesity
pancreas cancer
pancreatitis
primary tumor
staining
tumor growth
wild type mouse
endogenous compound
*glycine methyltransferase
Ki 67 antigen
Drug Index Terms
endogenous compound; *glycine methyltransferase; Ki 67 antigen
Other Index Terms
animal experiment; animal model; animal tissue; calorie; cancer size; cancer
staging; cancer susceptibility; cell proliferation; controlled study; fatty liver;
gene expression; hepatomegaly; *lipid diet; *liver cell carcinoma; liver weight;
microenvironment; mouse; murine model; nonhuman; nuclear magnetic resonance
imaging; obesity; pancreas cancer; pancreatitis; primary tumor; staining; tumor
growth; wild type mouse
Abstract
Introduction: Hepatocellular carcinoma (HCC) is the third leading cause of cancer
deaths worldwide. HCC typically arises in patients with chronic liver disease or
cirrhosis, yet it is increasingly associated with non-alcoholic fatty liver disease
(NAFLD), specifically nonalcoholic steatohepatitis (NASH) in the absence of
cirrhosis. NAFLD is associated with obesity, metabolic syndrome, and/or patients
with type II diabetes. Our previous studies have shown that high fat diet induced
hepatic steatosis increases proliferation of hepatocytes and the growth of
malignant tumors in a murine model. Glycine NMethylTransferase (GNMT) expression is
lost in over 95% of HCC, and mice deficient in GNMT develop spontaneous HCC by 6
months of age. We hypothesized that GNMT deficient mice would have an increased
susceptibility for the development and growth of HCC when a fed high fat diet.
Method(s): Wildtype and GNMT deficient mice were placed on lean diet (LD, 13%
calories from fat) or high fat diet (HFD, 42% calories from fat) at eight weeks of
age. An initial cohort of mice were sacrificed after 3 months on diet (6 months of
age) to assess for early tumor burden. A second cohort of mice was analyzed by
magnetic resonance imaging (MRI) after 6 months on diet (9 months of age) and then
sacrificed to assess for late stage disease. All mice were assessed for body
weight, liver weight, pancreatic weight, and proliferative index (Ki67). Result(s):
GNMT deficient mice failed to gain weight when placed on HFD, which remained at
levels equivalent to wildtype LD mice. At three months of age, wildtype mice on HFD
had significantly enlarged livers due to hepatic steatosis. HFD fed GNMT deficient
mouse livers were nearly 50% the size of wildtype livers and contained only minimal
fatty deposits. Further, livers from HFD and LD fed GNMT mice were equivalent after
3 months, yet they were larger than wildtype mice fed LD. After six months on diet,
MRI analysis showed significantly larger livers in HFD fed GNMT mice compared to LD
fed GNMT mice due to extensive tumor burden. All wildtype mice lacked any tumors
after six months regardless of diet. Histological analysis revealed a heightened
cellular proliferation via Ki67 staining in GNMT deficient livers compared to
wildtype livers. In comparison, GNMT silencing also occurs in pancreatic cancer,
yet none of the GNMT deficient mice developed pancreatic tumors. However, small
focal areas of pancreatitis were detected regardless of diet. Additionally,
pancreatic weight was significantly decreased in HFD fed GNMT deficient mice
compared the LD GNMT deficient mice. Conclusion(s): While high fat diet did not
induce obesity in GNMT deficient mice, it significantly increased cellular
proliferation and primary tumor growth in the liver. Understanding dietary factors
that impact the microenvironment of the liver and contribute to HCC development and
progression is vital to finding new therapeutics for this malignancy.
7445&isbn=&volume=77&issue=13+Supplement+1&spage=2802&pages=&date=2017&title=Cancer
+Research&atitle=High+fat+diet+increases+development+of+hepatocellular+carcinoma+in
+glycine+N-methyltransferase+deficient+mice&aulast=VanSaun&pid=%3Cauthor
%3EVanSaun+M.N.%3BMendonsa+A.%3BMessaggio+F.%3BNagathihalli+N.%3BGorden+L.%3C
<83>
Accession Number
616959261
Title
Blackcurrant (Ribes nigrum) consumption prevents non-alcoholic steatohepatitis in
C57BL/6J mice with diet-induced obesity.
Source
FASEB Journal. Conference: Experimental Biology 2017, EB. Chicago, IL United
States. 31(1 Supplement 1) (no pagination), 2017. Date of Publication: April 2017.
Author
Lee Y.; Pham T.X.; Bae M.; Hu S.; O'Neill E.; Han C.; Caceres C.; Park Y.-K.; Lee
J.-Y.
Institution
(Lee, Pham, Bae, Hu, O'Neill, Han, Caceres, Park, Lee) Department of Nutritional
Sciences, University of Connecticut, Storrs, CT, United States
Publisher
FASEB
Subject Headings
animal cell
animal experiment
animal model
animal tissue
antiinflammatory activity
*black currant
bone marrow
*C57BL 6 mouse
control group
controlled study
gene expression regulation
genetic marker
liver weight
macrophage
male
monocyte
mouse
nonhuman
obesity
phenotype
plasma
powder
prevention
spleen
collagen type 1
endogenous compound
glycoprotein p 15095
mannose receptor
messenger RNA
microRNA 122
microRNA 192
sucrose
toll like receptor 4
transforming growth factor beta1
triacylglycerol
Drug Index Terms
alanine aminotransferase; collagen type 1; endogenous compound; glycoprotein p
15095; mannose receptor; messenger RNA; microRNA 122; microRNA 192; monocyte
chemotactic protein 1; sucrose; toll like receptor 4; transforming growth factor
beta1; triacylglycerol
Other Index Terms
animal cell; animal experiment; animal model; animal tissue; antiinflammatory
activity; *black currant; bone marrow; *C57BL 6 mouse; control group; controlled
study; *diet induced obesity; gene expression regulation; genetic marker; liver
weight; macrophage; male; monocyte; mouse; *nonalcoholic fatty liver; nonhuman;
obesity; phenotype; plasma; powder; prevention; spleen
Abstract
Non-alcoholic steatohepatitis (NASH) is characterized by excessive fat
accumulation and inflammation in the liver. NASH further progresses to cirrhosis
and hepatocellular carcinoma. With increased prevalence of NASH particularly in
obese population, preventative/therapeutic strategies for NASH are needed. To
investigate whether consumption of whole blackcurrant (Ribes nigrum) can prevent
the development of obesity-induced NASH, male C57BL/6J mice at age of 7 weeks were
fed one of the following 4 diets for 24 weeks: a low fat control (LF; 13 % energy
from fat); a LF with blackcurrant (LF-BC; 6% of freeze-dried whole blackcurrant
powder by weight); an obesogenic high fat/high sucrose control (HF/HS; 57%/28%
energy from fat/sucrose); and a HF/HS containing 6% blackcurrant powder (HF/HS-BC).
HF/HS markedly increased body weights of mice, and blackcurrant did not alter body
weights both in lean and obese mice. Hepatic triglyceride levels of HF/HS-BC group
were significantly lower than HF/HS control although liver weights were not
significantly different. Hepatic mRNA abundance of F4/80, a macrophage marker, was
significantly increased by HF/HS, which was attenuated by blackcurrant to the
similar level of LF groups. M1 macrophage markers, e.g., CD11c and monocyte
chemoattractant protein 1 (MCP-1), and fibrogenic genes, e.g., transforming growth
factor beta1 and collagen type I alpha 1, were significantly higher in HF/HS group
than HF/HS-BC group. Furthermore, blackcurrant significantly decreased the
expression of CD206, a M2 macrophage marker, MCP-1, and toll-like receptor 4 in
obese mice. The gene analysis demonstrated that blackcurrant attenuated obesity-
induced expression of proinflammatory and pro-fibrogenic genes. Using serum miRNA
array, we found that HF/HS significantly increased serum levels of miR-122-5p and
miR-192-5p, known serum markers of NAFLD, compared with LF control. However, the
levels were significantly lower in mice fed the HF/HS-BC diet. Additionally, plasma
alanine aminotransferase concentrations were significantly decreased by
blackcurrant consumption in both lean and obese mice at 16 and 24 weeks on the
experimental diets, supporting the protective role of blackcurrant in the
development of NASH. To gain insight into the anti-inflammatory effect of
blackcurrant, flow cytometric analysis was conducted for the determination of
monocyte phenotypes in the spleen and bone marrow. There were no significant
differences in Ly6C- to Ly6C+ ratios and total numbers of bone marrow monocytes.
However, in the spleen, HF/HS diet significantly decreased the ratios of Ly6C- to
Ly6C+ monocytes while significantly increasing the number of total splenic
monocytes compared with LF control. The increased number of total splenic monocytes
by HF/HS was significantly attenuated by blackcurrant. Taken together, our data
indicate that whole blackcurrant exerts anti-inflammatory and anti-fibrotic actions
in obese mice with NASH, at least in part, by preventing an increase in splenic
monocyte population induced by obesity. Therefore, blackcurrant consumption may be
beneficial for the prevention of NASH in obese population.
6860&isbn=&volume=31&issue=1+Supplement+1&spage=&pages=&date=2017&title=FASEB+Journ
al&atitle=Blackcurrant+%28Ribes+nigrum%29+consumption+prevents+non-
alcoholic+steatohepatitis+in+C57BL%2F6J+mice+with+diet-
induced+obesity&aulast=Lee&pid=%3Cauthor%3ELee+Y.%3BPham+T.X.%3BBae+M.%3BHu+S.%3BO
%27Neill+E.%3BHan+C.%3BCaceres+C.%3BPark+Y.-K.%3BLee+J.-Y.%3C%2Fauthor%3E%3CAN
<84>
Accession Number
616802179
Title
Obesity and alcohol as synergistic risk factors for hepatocellular carcinoma.
Source
Alcoholism: Clinical and Experimental Research. Conference: 40th Annual
Scientific Meeting of the Research Society on Alcoholism. Denver, CO United States.
41(Supplement 1) (pp 291A), 2017. Date of Publication: June 2017.
Author
Thompson K.J.; McKillop I.H.
Institution
(Thompson, McKillop) Department of Surgery, Carolinas Medical Center, Charlotte,
NC 28209, United States
Publisher
Subject Headings
alcohol consumption
animal cell
animal experiment
animal model
animal tissue
carcinogenesis
cell proliferation
disease course
fatty liver
female
global health
glycolysis
*hepatocellular carcinoma cell line
human versus animal comparison
liver cirrhosis
male
mediator
mitochondrion
nonhuman
*obesity
oxidative phosphorylation
phenotype
*risk factor
stem cell culture
tumor model
*alcohol
drinking water
endogenous compound
fatty acid binding protein 4
mitogen activated protein kinase
mitogen activated protein kinase 1
mitogen activated protein kinase 3
Drug Index Terms
*alcohol; drinking water; endogenous compound; fatty acid binding protein 4;
mitogen activated protein kinase; mitogen activated protein kinase 1; mitogen
activated protein kinase 3
Other Index Terms
alcohol consumption; animal cell; animal experiment; animal model; animal tissue;
carcinogenesis; cell proliferation; disease course; fatty liver; female; global
health; glycolysis; *hepatocellular carcinoma cell line; human versus animal
comparison; liver cell carcinoma; liver cirrhosis; male; mediator; mitochondrion;
nonhuman; *obesity; oxidative phosphorylation; phenotype; *risk factor; stem cell
culture; tumor model
Abstract
Hepatocellular carcinoma (HCC) is 5th most common cancer diagnosed and the 3rd
leading cause of cancer related mortality. Incidence of HCC is directly linked with
exposure to known risk factors, including sustained-heavy alcohol intake, viral
hepatitis infection, and more recently, obesity. Despite differences in the
mechanisms that mediate hepatic damage following chronic ethanol intake and
obesity, these pre-neoplastic pathogeneses exhibit many shared characteristics.
Analysis of metabolic pathways reveals a convergence toward a shared phenotype
characterized by changes from mitochondrial oxidative phosphorylation toward b-
oxidation/cellular glycolysis, independent of underlying cirrhosis. To evaluate
potential pathways involved in the synergism between alcohol and obesity, we
employed a mousemodel of obesity-associated HCC with DEN initiation, with a subset
of animals placed on an 8-week alcohol/drinking water regiment. Using this approach
we identified fatty acid binding protein-4 (FABP4), a FABP not normally expressed
in liver, as a potential mediator of HCC progression in the settings of both
obesity and chronic alcohol intake. In vitro cell culture experiments demonstrated
lipid-laden HCC cell lines produce-secrete FABP4, while exogenous FABP4
administration stimulated proliferation and migration of HCC cells via an Erk1/2-
MAPK pathway. These data suggest hepatic steatosis, resulting from either chronic
alcohol intake or obesity, produce a common mediator that acts on transformed
hepatocytes and promotes tumorigenesis. Preliminary analyses of serum and tissue
from obese and lean HCC patients support these data from mouse and HCC cell culture
models. Considering the global health impact of alcohol and obesity, understanding
the mechanisms that drive hepatic pathogenesis toward HCC are of critical
importance.
sid=OVID:embase&id=pmid:&id=doi:10.1111%2Facer.13392&issn=1530-
0277&isbn=&volume=41&issue=Supplement+1&spage=291A&pages=291A&date=2017&title=Alcoh
olism
%3A+Clinical+and+Experimental+Research&atitle=Obesity+and+alcohol+as+synergistic+ri
sk+factors+for+hepatocellular+carcinoma&aulast=Thompson&pid=%3Cauthor
%3EThompson+K.J.%3BMcKillop+I.H.%3C%2Fauthor%3E%3CAN%3E616802179%3C%2FAN%3E%3CDT
<85>
Accession Number
610202262
PMID
Title
Oncogenic mutations and dysregulated pathways in obesity-associated
Source
Oncogene. 35(49) (pp 6271-6280), 2016. Date of Publication: 08 Dec 2016.
Author
Shen J.; Tsoi H.; Liang Q.; Chu E.S.H.; Liu D.; Yu A.C.-S.; Chan T.F.; Li X.;
Sung J.J.Y.; Wong V.W.S.; Yu J.
Author NameID
Li X.; ORCID: https://orcid.org/0000-0001-8791-7505
Institution
(Shen, Tsoi, Liang, Chu, Liu, Li, Sung, Wong, Yu) Institute of Digestive Disease,
Department of Medicine and Therapeutics, Chinese University of Hong Kong, 30-32
Ngan Shing Street, Hong Kong, Hong Kong
(Yu, Chan) School of Life Sciences, State Key Laboratory of Agrobiotechnology,
Chinese University of Hong Kong, Hong Kong, Hong Kong
Publisher
Nature Publishing Group (Houndmills, Basingstoke, Hampshire RG21 6XS, United
Kingdom)
Subject Headings
animal cell
animal experiment
animal model
article
cancer size
cell proliferation
codon
colony formation
controlled study
disease association
endoplasmic reticulum stress
enzyme activation
exome
gain of function mutation
gene frequency
*gene mutation
gene silencing
human
human cell
lipid diet
liver cell
liver weight
loss of function mutation
male
mouse
nonhuman
*obesity
*oncogene
oncogene H ras
priority journal
virus oncogene
cholesterol ester/ec [Endogenous Compound]
diethylnitrosamine
mitogen activated protein kinase/ec [Endogenous Compound]
phosphatidylinositol 4,5 bisphosphate 3 kinase/ec [Endogenous Compound]
phosphoinositide dependent protein kinase 1/ec [Endogenous Compound]
protein IRE1/ec [Endogenous Compound]
protein kinase B/ec [Endogenous Compound]
Ras protein/ec [Endogenous Compound]
stress activated protein kinase/ec [Endogenous Compound]
transcription factor AP 1/ec [Endogenous Compound]
carboxyl ester lipase gene
Candidate Terms
carboxyl ester lipase gene [other term]
Drug Index Terms
cholesterol ester / endogenous compound; diethylnitrosamine; mitogen activated
protein kinase / endogenous compound; phosphatidylinositol 4,5 bisphosphate 3
kinase / endogenous compound; phosphoinositide dependent protein kinase 1 /
endogenous compound; protein IRE1 / endogenous compound; protein kinase B /
endogenous compound; Ras protein / endogenous compound; stress activated protein
kinase / endogenous compound; transcription factor AP 1 / endogenous compound
Other Index Terms
animal cell; animal experiment; animal model; Article; cancer size; cell
proliferation; codon; colony formation; controlled study; disease association;
endoplasmic reticulum stress; enzyme activation; exome; gain of function mutation;
gene frequency; *gene mutation; gene silencing; human; human cell; lipid diet;
*liver carcinogenesis; liver cell; *liver cell carcinoma / *etiology; liver weight;
loss of function mutation; male; mouse; nonalcoholic fatty liver; nonhuman;
*obesity; *oncogene; oncogene H ras; priority journal; virus oncogene
Abstract
Epidemiological studies showed that obesity and its related non-alcoholic fatty
liver disease (NAFLD) promote hepatocellular carcinoma (HCC) development. We aimed
to uncover the genetic alterations of NAFLD-HCC using whole-exome sequencing. We
compared HCC development in genetically obese mice and dietary obese mice with
wild-type lean mice fed a normal chow after treatment with diethylnitrosamine. HCC
tumor and adjacent normal samples from obese and lean mice were then subjected to
whole-exome sequencing. Functional and mechanistic importance of the identified
mutations in Carboxyl ester lipase (Cel) gene and Harvey rat sarcoma virus oncogene
1 (Hras) was further elucidated. We demonstrated significantly higher incidences of
HCC in both genetic and dietary obese mice with NAFLD development as compared with
lean mice without NAFLD. The mutational signatures of NAFLD-HCC and lean HCC were
distinct, with <3% overlapped. Eight metabolic or oncogenic pathways were found to
be significantly enriched by mutated genes in NAFLD-HCC, but only two of these
pathways were dysregulated by mutations in lean HCC. In particular, Cel was mutated
significantly more frequently in NAFLD-HCC than in lean HCC. The multiple-site
mutations in Cel are loss-of-function mutations, with effects similar to Cel knock-
down. Mutant Cel caused accumulation of cholesteryl ester in liver cells, which led
to induction of endoplasmic reticulum stress and consequently activated the
IRE1alpha/c-Jun N-terminal kinase (JNK)/c-Jun/activating protein-1 (AP-1) signaling
cascade to promote liver cell growth. In addition, single-site mutations in Hras at
codon 61 were found in NAFLD-HCC but none in lean HCC. The gain-of-function
mutations in Hras (Q61R and Q61K) significantly promoted liver cell growth through
activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-
4,5-bisphosphate 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1
(PDK1)/Akt pathways. In conclusion, we have identified mutation signature and
pathways in NAFLD-associated HCC. Mutations in Cel and Hras have important roles in
NAFLD-associated hepatocellular carcinogenesis.Copyright © 2016 Macmillan
Publishers Limited, part of Springer Nature.
sid=OVID:embase&id=pmid:27132506&id=doi:10.1038%2Fonc.2016.162&issn=0950-
6280&date=2016&title=Oncogene&atitle=Oncogenic+mutations+and+dysregulated+pathways+
in+obesity-associated+hepatocellular+carcinoma&aulast=Shen&pid=%3Cauthor%3EShen+J.
%3BTsoi+H.%3BLiang+Q.%3BChu+E.S.H.%3BLiu+D.%3BYu+A.C.-S.%3BChan+T.F.%3BLi+X.
%3BSung+J.J.Y.%3BWong+V.W.S.%3BYu+J.%3C%2Fauthor%3E%3CAN%3E610202262%3C%2FAN%3E
%3CDT%3EArticle%3C%2FDT%3E
<86>
Accession Number
612868146
Title
Obesity is protective factor in hepatocellular carcinoma.
Source
American Journal of Gastroenterology. Conference: 81st Annual Scientific Meeting
of the American College of Gastroenterology. Las Vegas, NV United States.
111(Supplement 1) (pp S343), 2016. Date of Publication: October 2016.
Author
Wang Y.; Attar B.M.; Bedrose S.; Hinami K.; Krishnan J.; Simons-Linares C.R.
Institution
(Wang, Attar, Bedrose, Hinami, Krishnan, Simons-Linares) Cook County Health and
Hospital Systems, Chicago, IL, United States
Publisher
Nature Publishing Group
Subject Headings
body mass
cancer size
controlled study
diagnosis
histology
hospice
human
human tissue
ICD-9
liver biopsy
liver cirrhosis
liver metastasis
mortality
*obesity
paracentesis
prevalence
prognosis
public hospital
risk factor
statistical model
underweight
vein embolism
Other Index Terms
body mass; cancer size; controlled study; diagnosis; histology; hospice; human;
human tissue; ICD-9; liver biopsy; *liver cell carcinoma; liver cirrhosis; liver
metastasis; major clinical study; mortality; nonalcoholic fatty liver; *obesity;
paracentesis; prevalence; prognosis; public hospital; risk factor; statistical
model; underweight; vein embolism
Abstract
Introduction: The incidence of hepatocellular carcinoma (HCC) has been increasing
significantly with the nationwide epidemic of obesity. The relationship between
obesity, metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) is well
established. However, as HCC is heterogeneous regarding etiology and severity of
concurrent cirrhosis, the overall role of obesity in HCC warrants more
investigation. This study aims to characterize prevalence of obesity in HCC
patients, assess association of obesity with tumor characterstics and prognosis.
Method(s): We retrospectively analyzed patients with diagnosis of hepatocellular
carcinoma (by ICD-9 code) at a large public hospital during 10 years (05/2006
through 05/2015). HCC was confirmed with characteristic radiologic features and/or
histology from liver biopsy. Patients are categorized according to body weight
index (BMI) at diagnosis of HCC as underweight (2), normal weight (18.5-24.9
kg/m2), overweight (25-29.9 kg/m2), Class I Obesity (30-34.9 kg/m2), Class II
Obesity (35-39.9 kg/m2), Class III Obesity (>= 40 kg/m2). HCC is categorized
according to etiology into viral, alcoholic, viral-alcoholic, nonviral-
nonalcoholic. We constructed multivariable regression model of mortality with STATA
13. Result(s): 270 patients were included of which 13(4.81%) were underweight,
99(36.7%) normal weight, 78(28.9%) overweight, 50 (18.5%) Class I obese, 15(5.6%)
Class II obese, 15(5.6%) Class III obese. There was no difference in mean BMI by
severity of cirrhosis. However there was significant difference of mean BMI by
etiology (p < 0.0001): nonviral-nonalcoholic HCC showed significant higher BMI.
Higher BMI is associated with extra-hepatic metastasis (p=0.026), however there's
no difference in tumor number and size. BMI is independent risk factor for venous
thromboembolic event (VTE) (OR 1.15, p=0.020; CI 1.02- 1.29), and independent
protective factor for mortality (OR=0.92 p=0.038; CI: 0.84-0.99). After exclusion
of patients with prior paracentesis (70/270), protective effect of BMI persists (OR
0.86, p=0.007; CI 0.77-0.96). Conclusion(s): Patients with HCC of different
etiologies have significantly different BMI: nonviral-nonalcoholic- HCC which
mostly represent (NAFLD) is associated with higher BMI. Higher BMI is associated
with extra-hepatic metastasis and risk of VTE. BMI is not risk factor for hospice
or preclusion from curative treatment. However interestingly higher BMI showed
protective effect against mortality.
sid=OVID:embase&id=pmid:&id=doi:10.1038%2Fajg.2016.359&issn=1572-
0241&isbn=&volume=111&issue=Supplement+1&spage=S343&pages=S343&date=2016&title=Amer
ican+Journal+of+Gastroenterology&atitle=Obesity+is+protective+factor+in+hepatocellu
lar+carcinoma&aulast=Wang&pid=%3Cauthor%3EWang+Y.%3BAttar+B.M.%3BBedrose+S.
%3BHinami+K.%3BKrishnan+J.%3BSimons-Linares+C.R.%3C%2Fauthor%3E%3CAN%3E612868146%3C
<87>
Accession Number
72272944
Title
Lean patients with nonalcoholic fatty liver disease have worse survival compared
to non-lean patients.
Source
Gastroenterology. Conference: Digestive Disease Week 2016, DDW 2016. San Diego,
CA United States. Conference Publication: (var.pagings). 150(4 SUPPL. 1) (pp
S1148), 2016. Date of Publication: April 2016.
Author
Young S.; Mansour W.; Hoppmann N.A.; Reddy S.B.; Arora S.; Singal A.K.
Publisher
W.B. Saunders
Subject Headings
*human
*patient
*survival
*gastrointestinal disease
liver cirrhosis
cerebrovascular disease
model
liver biopsy
logistic regression analysis
body mass
chi square test
Student t test
diabetes mellitus
dyslipidemia
hypertension
mortality
etiology
ultrasound
steatosis
United States
liver disease
Caucasian
diagnosis
atherosclerosis
prospective study
prevalence
risk
follow up
obesity
female
Other Index Terms
*human; *patient; *survival; *gastrointestinal disease; *nonalcoholic fatty
liver; liver cirrhosis; cerebrovascular disease; model; liver biopsy; logistic
regression analysis; body mass; chi square test; liver transplantation; Student t
test; diabetes mellitus; dyslipidemia; hypertension; mortality; liver cell
carcinoma; etiology; ultrasound; steatosis; United States; liver disease;
Caucasian; diagnosis; atherosclerosis; prospective study; prevalence; risk; follow
up; obesity; female
Abstract
Introduction: Due to the rising incidence of obesity in the United States,
nonalcoholic fatty liver disease (NAFLD) is rapidly growing as an etiology of
cirrhosis and indication for liver transplantation. However, a group of NAFLD
patients are lean (body mass index [BMI] below 25). Data on NAFLD characteristics
and their survival in lean patients are scanty. Method(s): We performed this study
on a cohort of NAFLD patients enrolling in a prospective study at our center.
Diagnosis of NAFLD was based on excluding other causes of liver disease and
presence of steatosis on ultrasound or liver biopsy. Nonalcoholic steatohepatitis
(NASH) was diagnosed based on liver biopsy with NAFLD activity score (NAS) of >4.
NAFLD patients were stratified to lean and non-lean based on BMI cut-off at 25.
Baseline characteristics were compared using t-test for continuous variables and
Chi-square test for categorical variables. Logistic regression model was used for
predictors. Result(s): Of 126 NAFLD patients (mean age 60 years old, 61% females,
88% Caucasian, mean BMI 33, 60% cirrhosis, 43% with features of decompensation, 6%
hepatocellular carcinoma, 11% NASH without cirrhosis, 63% diabetes mellitus [DM],
56% dyslipidemia, 66% hypertension, 23% atherosclerosis including coronary or
peripheral arterial or cerebrovascular disease), 11 (8.7%) patients were lean.
Compared to 115 non-lean, 11 lean NAFLD patients had a lower BMI (22+/-2.3 vs 34+/-
5.8, p <0.0001) and higher frequency of cerebrovascular disease (18 vs 2%,
p=0.003). Overall mortality in this cohort was 17% with lower survival among lean
patients compared to non-lean patients (55 vs 85%, p=0.0007). In a logistic
regression analysis model after controlling for patient age, cerebrovascular
disease, cirrhosis, and DM, lean compared to non-lean NAFLD patients had over 9
fold higher risk for dying on follow up (Table). Discussion(s): Prevalence of lean
NAFLD in this cohort is around 9%. Lean NAFLD patients compared to non-lean NAFLD
patients have worse survival. Future studies are suggested to examine mechanisms of
NAFLD in lean patients and for developing strategies for improving outcome of lean
NAFLD patients. (Table Presented).
sid=OVID:embase&id=pmid:&id=doi:&issn=0016-5085&isbn=&volume=150&issue=4+SUPPL.
+1&spage=S1148&pages=S1148&date=2016&title=Gastroenterology&atitle=Lean+patients+wi
th+nonalcoholic+fatty+liver+disease+have+worse+survival+compared+to+non-
lean+patients&aulast=Young&pid=%3Cauthor%3EYoung+S.%3BMansour+W.%3BHoppmann+N.A.
%3BReddy+S.B.%3BArora+S.%3BSingal+A.K.%3C%2Fauthor%3E%3CAN%3E72272944%3C%2FAN%3E
<88>
Accession Number
611946090
PMID
Title
Alcohol and Obesity: A Dangerous Association for Fatty Liver Disease.
Source
Digestive Diseases. 34(1 Supplement 1) (pp 32-39), 2016. Date of Publication: 01
Aug 2016.
Author
Mahli A.; Hellerbrand C.
Institution
(Mahli, Hellerbrand) Department of Internal Medicine i, University Hospital
Regensburg, Regensburg DE-93053, Germany
Publisher
S. Karger AG
Subject Headings
alcohol liver disease/ep [Epidemiology]
article
disease association
*fatty liver
human
lipid diet
liver cell
liver injury
nonalcoholic fatty liver/ep [Epidemiology]
nonhuman
*obesity
priority journal
*alcohol
Drug Index Terms
*alcohol
Other Index Terms
alcohol liver disease / epidemiology; Article; disease association; *fatty liver;
human; lipid diet; liver cell; liver injury; metabolic syndrome X; nonalcoholic
fatty liver / epidemiology; nonhuman; *obesity; priority journal
Abstract
Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are
the most frequent chronic liver disorders, and their advanced forms - alcoholic
steatohepatitis and nonalcoholic steatohepatitis - are the most frequent conditions
leading to liver cirrhosis and hepatocellular carcinoma worldwide. NAFLD is
considered as the hepatic manifestation of the metabolic syndrome. With the
pandemic rise of obesity, the incidence of NAFLD is also further increasing, and
considering the life style in modern societies, there is a significant overlap of
(risk factors causing) NAFLD and (alcohol consumption predisposing for) ALD at
least in Western countries. Epidemiological studies propose a causative link
between chronic alcohol consumption and progressive liver disease in obese
individuals. Furthermore, experimental studies indicate combined pathological
effects of alcohol and obesity or fatty acid levels, respectively, on
hepatocellular lipid accumulation and injury as well as hepatic inflammation,
fibrosis and cancerogenesis. Notably, these combined pathological effects are in
part additive but partly even synergistic. And importantly, alcohol does already
exhibit synergistic pathological effects with obesity at moderate doses. This
indicates significant differences in the dose threshold for hepatotoxic alcohol
effects in lean and obese subjects and herewith also has important implications for
recommendations for 'safe' alcohol consumption. The purpose of this brief review is
to update the knowledge on the combined effects of alcohol and obesity on the
development and progression of liver disease. Undoubtedly, alcohol and the
metabolic syndrome appear as a dangerous mix, and there are important interactive
effects of either condition with regard to crucial triggers of liver
injury.Copyright © 2016 S. Karger AG, Basel.
sid=OVID:embase&id=pmid:27548267&id=doi:10.1159%2F000447279&issn=0257-
2753&isbn=&volume=34&issue=1+Supplement+1&spage=32&pages=32-
39&date=2016&title=Digestive+Diseases&atitle=Alcohol+and+Obesity
%3A+A+Dangerous+Association+for+Fatty+Liver+Disease&aulast=Mahli&pid=%3Cauthor
%3EMahli+A.%3BHellerbrand+C.%3C%2Fauthor%3E%3CAN%3E611946090%3C%2FAN%3E%3CDT
<89>
Accession Number
621266771
Title
Obesity and alcohol as independent and co-morbid risk factors for HCC.
Source
Alcohol and Alcoholism. Conference: 15th European Society for Biomedical Research
on Alcoholism Congress, ESBRA 2015. Valencia Spain. 50(Supplement 1) (pp i17),
2015. Date of Publication: September 2015.
Author
Thompson K.; Iannitti D.A.; Swan R.Z.; Schrum L.W.; McKillop I.H.
Institution
(Thompson, Iannitti, Swan, McKillop) Department of Surgery, United States
(Schrum) Department of Medicine, Carolinas Medical Center, Charlotte, NC, United
States
Publisher
Oxford University Press
Subject Headings
adipocyte
adult
alcohol consumption
animal cell
animal experiment
animal model
cell proliferation
feeding
female
glycolysis
hepatoma cell
incidence
lipid transport
liver cirrhosis
male
metabolomics
mitochondrial respiration
mouse
mouse model
nonhuman
*obesity
phenotype
protein expression
*risk factor
stem cell culture
storage
stress
acyl coenzyme A
*alcohol
carboxylase
endogenous compound
fatty acid
fatty acid binding protein 4
fatty acid synthase
sirtuin 1
conference abstract
Candidate Terms
Drug Index Terms
acyl coenzyme A; *alcohol; carboxylase; endogenous compound; fatty acid; fatty
acid binding protein 4; fatty acid synthase; sirtuin 1
Other Index Terms
adipocyte; adult; alcohol consumption; animal cell; animal experiment; animal
model; cell proliferation; fatty acid oxidation; feeding; female; glycolysis;
hepatoma cell; incidence; lipid transport; liver cell carcinoma; liver cirrhosis;
male; metabolomics; mitochondrial respiration; mouse; mouse model; nonalcoholic
fatty liver; nonhuman; *obesity; phenotype; protein expression; *risk factor; stem
cell culture; storage; stress
Abstract
The incidence of hepatocellular carcinoma (HCC) has increased steadily over the
last 30-years without significant improvements in patient outcomes. HCC incidence
is linked to known risk factors including chronic alcohol intake and obesity.
Despite differences in the chemical nature of these insults the precancerous
pathogeneses share many similarities. Metabolomics reveals convergence towarda core
phenotype involving the switch from mitochondrial oxidation toward
beta-oxidation/cellular glycolysis independent of underlying cirrhosis. We employed
mouse models of obesity, chronic alcohol feeding and obesity concomitant with
alcohol to study these events. Both alcohol and obesity accelerated DEN-induced
HCC, although only obesity induced HCC independent of DEN-initiation. We next
analyzed pathways that may mediate these events. Sirt1 deacetylase activity
decreased during progression toward a lipogenic phenotype (elevated fatty acid
synthase, acyl-coA carboxylase) and increased fatty acid binding-protein (FABP)
expression. Significantly, FABP4, normally associated with lipid transport/storage
in adipocytes, was elevated in HCC with underlying NAFLD/obesity. Cell culture
models demonstrated hepatoma cells treated with fatty acids had significantly
increased FABP4 expression and proliferation, effects abrogated by blocking FABP4.
These data suggest hepatosteatosis, resulting from either chronic alcohol intake or
obesity, impact similar pathways involved in intracellular fat utilization and/or
storage. In turn, hepatic stress induced by alcohol enhances hepatocyte
transformation resulting from obesity-induced hepa-tosteatosis. Preliminary
analyses of human hepatomas from obese and lean patients support data from these
mouse models. Given the impending health consequences of obesity and continued
(ab)use of alcohol, understanding these mechanisms are critical in averting hepatic
disease and further increases in HCC incidence.
sid=OVID:embase&id=pmid:&id=doi:10.1093%2Falcalc%2Fagv076.60&issn=1464-
3502&isbn=&volume=50&issue=Supplement+1&spage=i17&pages=i17&date=2015&title=Alcohol
+and+Alcoholism&atitle=Obesity+and+alcohol+as+independent+and+co-
morbid+risk+factors+for+HCC&aulast=Thompson&pid=%3Cauthor%3EThompson+K.
%3BIannitti+D.A.%3BSwan+R.Z.%3BSchrum+L.W.%3BMcKillop+I.H.%3C%2Fauthor%3E%3CAN
<90>
Accession Number
72298293
Title
Role of nutrition in non-alcoholic fatty liver disease.
Source
Annals of Nutrition and Metabolism. Conference: 12th European Nutrition
Conference, FENS 2015. Berlin Germany. Conference Publication: (var.pagings).
67(SUPPL. 1) (pp 91), 2015. Date of Publication: October 2015.
Author
Peter S.; Weber P.
Institution
(Peter, Weber) DSM Nutritional Products, Kaiseraugst, Switzerland
Publisher
S. Karger AG
Subject Headings
*nutrition
*European
human
patient
fatty liver
liver
liver disease
obesity
risk
lipid storage
steatosis
drug therapy
liver cirrhosis
alcohol consumption
weight
caloric intake
prevalence
alcoholic fatty liver
tissue injury
risk factor
dyslipidemia
inflammation
chronic kidney disease
liver cell damage
insulin resistance
oxidative stress
death
clinical trial (topic)
fibrosis
cell damage
chronic inflammation
public health
alpha tocopherol
trace element
scavenger
vitamin
antioxidant
peroxy radical
Drug Index Terms
alpha tocopherol; trace element; scavenger; vitamin; antioxidant; peroxy radical
Other Index Terms
*nutrition; *European; *nonalcoholic fatty liver; human; patient; fatty liver;
liver; liver disease; non insulin dependent diabetes mellitus; obesity; risk; lipid
storage; steatosis; drug therapy; liver cirrhosis; alcohol consumption; liver cell
carcinoma; weight; caloric intake; prevalence; alcoholic fatty liver; tissue
injury; risk factor; dyslipidemia; inflammation; chronic kidney disease; liver cell
damage; liver transplantation; insulin resistance; chronic liver disease; oxidative
stress; death; clinical trial (topic); fibrosis; cell damage; chronic inflammation;
public health
Abstract
Fatty liver is a global and unresolved public health issue, which encompass a
wide spectrum of liver tissue injury, ranging from steatosis to steatohepatitis,
fibrosis and cirrhosis. We differentiate alcoholic fatty liver disease caused by
heavy alcohol consumption from nonalcoholic fatty liver disease (NAFLD) which is
the result of ectopic fat accumulation in the liver. NAFLD patients may develop
non-alcoholic steatohepatitis (NASH) which is a progression of steatosis to liver
cell injury and inflammation in addition to excessive fat accumulation. About 15-
20% of NASH patients will even develop liver cirrhosis, which is a considerable
risk factor for hepatocellular carcinoma, cardiovascular and liver death. During
the past decade NAFLD has become the most common cause of chronic liver disease in
Western countries and is predicted to become also the most frequent indication for
liver transplantation by 2030. There is emerging evidence that NAFLD affects extra-
hepatic organs and regulatory pathways in a complex interplay which may increase
the risk of type 2 diabetes mellitus, cardiovascular and chronic kidney diseases.
Furthermore, NAFLD is frequently associated with obesity, dyslipidaemia, insulin
resistance and type 2 diabetes mellitus. Its prevalence can reach 86% in obese
persons, but it can also be observed in 16% to 20% of normal weight individuals.
With advancing age biochemical and histological changes in subjects with fatty
liver are reported to be more severe. So far no drug treatment has been established
for patients with fatty liver disease. However, nutrition is considered as an
important element in reducing the risk to develop NAFLD as well as impacting on
established NAFLD and NASH. Besides general dietary interventions such as
normalizing caloric intakes to reduce overweight and the respective metabolic
consequences there is in addition encouraging data that particular micronutrients
such as vitamin E can beneficially impact the course of fatty liver disease.
Vitamin E has been shown in several randomized clinical trials (400-800 IU vitamin
E/day) to improve biochemical, pathophysiological and histological status of NAFLD/
NASH patients. Concerning the underlying mechanism of action, vitamin E, an
essential antioxidant and a powerful peroxyl radical scavenger, might reduce
oxidative stress along with consequent cellular injury and chronic inflammation. In
conclusion, there is encouraging evidence that micronutrients such as vitamin E can
benefit patients with NAFLD/NASH which is of particular value as there is no drug
treatment established yet.
9697&isbn=&volume=67&issue=SUPPL.
+1&spage=91&pages=91&date=2015&title=Annals+of+Nutrition+and+Metabolism&atitle=Role
+of+nutrition+in+non-alcoholic+fatty+liver+disease&aulast=Peter&pid=%3Cauthor
%3EPeter+S.%3BWeber+P.%3C%2Fauthor%3E%3CAN%3E72298293%3C%2FAN%3E%3CDT
<91>
Accession Number
72265921
Title
Genomic mutations and pathways identified by whole-exome sequencing in nafld-
associated hepatocellular carcinoma.
Source
United European Gastroenterology Journal. Conference: 23rd United European
Gastroenterology Week. Barcelona Spain. Conference Publication: (var.pagings). 3(5
SUPPL. 1) (pp A109), 2015. Date of Publication: October 2015.
Author
Yu J.; Shen J.; Tsoi H.; Liang Q.; Wong V.W.; Sung J.J.
Institution
(Yu, Shen, Tsoi, Liang, Wong, Sung) Institute of Digestive Disease, Department of
Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong
Publisher
Subject Headings
*exome
*European
*gastroenterology
*mutation
mouse
gene
mouse mutant
neoplasm
obesity
cell growth
species
cancer incidence
carcinogenesis
tumor volume
landscape
diet
liver cell
codon
wild type
mutation rate
liver tumor
endoplasmic reticulum stress
wild type mouse
lipid diet
diethylnitrosamine
cholesterol ester
Drug Index Terms
diethylnitrosamine; cholesterol ester
Other Index Terms
*exome; *liver cell carcinoma; *European; *gastroenterology; *mutation; mouse;
gene; mouse mutant; neoplasm; obesity; cell growth; species; cancer incidence;
carcinogenesis; tumor volume; landscape; nonalcoholic fatty liver; diet; liver
cell; codon; wild type; mutation rate; liver tumor; endoplasmic reticulum stress;
wild type mouse; lipid diet
Abstract
Introduction: Epidemiological studies have shown that obesity and its related
non-alcoholic fatty liver disease (NAFLD) promotes the development of
hepatocellular carcinoma (HCC). However, the underlying genetic mechanism of obese-
related HCC is still largely unknown. Aims & Methods: We aimed to uncover the
genetic alterations of obesity-associated HCC using cross-species oncogenomics and
whole-exome sequencing. HCC development in genetic obese (db/db) mice and dietary
obese mice kept on high-fat diet was monitored in comparison with wild-type lean
mice kept on normal diet treated with diethylnitrosamine (DEN). Paired HCC tumor
and adjacent normal samples from obese mice and lean mice were subjected to whole-
exome sequencing and cross-species oncogenomics to reveal genetic alteration
landscapes. Candidate mutation genes were further validated in HCC tumor and
adjacent normal samples from 16 genetic and 13 dietary obese mice and 16 control
lean mice by PCR Sanger sequencing. The bio-functional significance and molecular
pathways of the candidate mutation genes was evaluated. Result(s): Significantly
higher tumor incidence, multiplicity and larger tumor size of NAFLD-HCCs were found
in both genetic and dietary obese mice compared with those of lean HCCs in wild-
type mice. Totally 277 and 268 genes were found to be mutated in liver tumors from
obese mice and control lean mice, respectively, with only 8 genes overlapped by
whole-exome sequencing. Eight important metabolic or cancer-related pathways were
significantly enriched in mutated genes found in obese HCC, whereas only two
pathways were enriched in mutated genes found in lean HCC. Mutation frequency of
Cel was significantly higher in obese HCC than in lean HCC (34.5% vs. 6.3%,
P<0.05). Mutations in hRas were detected in 10.3% of obese HCCs, all located at
codon 61, but not in lean HCCs. CEL inactivating mutation and hras activating
mutation promote liver cell growth. Inactivating mutation in CEL (D454E and D555N)
led to the accumulation of cholesteryl ester, which activated ER stress and
consequent IRE1alpha/ JNK/c-Jun/AP-1 signalling cascade; whist activating mutations
in hRas (Q61R and Q61K) activated MAPK and PI3K/PDK1/Akt signaling cascades to
promote cell growth. Conclusion(s): The genetic alterations of NAFLD-associated HCC
are distinguished from that of lean HCC. Mutations in CEL and hRas play important
roles in NAFLD-associated hepatocellular carcinogenesis.
6406&isbn=&volume=3&issue=5+SUPPL.
+1&spage=A109&pages=A109&date=2015&title=United+European+Gastroenterology+Journal&a
title=Genomic+mutations+and+pathways+identified+by+whole-exome+sequencing+in+nafld-
associated+hepatocellular+carcinoma&aulast=Yu&pid=%3Cauthor%3EYu+J.%3BShen+J.
%3BTsoi+H.%3BLiang+Q.%3BWong+V.W.%3BSung+J.J.%3C%2Fauthor%3E%3CAN%3E72265921%3C
<92>
Accession Number
72079846
Title
Prevalence of diabetes and associating factors in patients with chronic hepatitis
C virus (HCV) infection: Comparison of a Chinese and an American cohort.
Source
Study of Liver Diseases: The Liver Meeting 2015. San Francisco, CA United States.
Conference Publication: (var.pagings). 62(SUPPL. 1) (pp 1125A), 2015. Date of
Author
Rao H.; Wu E.; Fu S.; Yang M.; Feng B.; Lin A.; Fei R.; Fontana R.J.; Lok A.S.;
Wei L.
Institution
(Rao, Yang, Feng, Fei, Wei) Peking University, People's Hospital, Hepatology
Institute, Beijing, China
(Wu, Fu, Fontana, Lok) Department of Internal Medicine, Division of
Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor,
MI, United States
(Lin) Molecular and Behavioral Neuroscience Institute, University of Michigan,
Ann Arbor, MI, United States
Publisher
Subject Headings
*American
*prevalence
*chronic hepatitis C
*diabetes mellitus
*human
*patient
*Hepatitis C virus
*liver disease
*liver
*virus infection
obesity
China
risk
liver cirrhosis
infection
disease severity
prospective study
waist circumference
multivariate analysis
male
United States
glucose blood level
diagnosis
fatty liver
antivirus agent
Drug Index Terms
antivirus agent
Other Index Terms
*American; *prevalence; *chronic hepatitis C; *diabetes mellitus; *human;
*patient; *Hepatitis C virus; *liver disease; *liver; *virus infection; obesity;
China; risk; liver cirrhosis; infection; disease severity; prospective study; waist
circumference; multivariate analysis; male; liver cell carcinoma; United States;
glucose blood level; diagnosis; fatty liver
Abstract
Background: Diabetes and hepatic steatosis are associated with increased risk of
cirrhosis and hepatocellular carcinoma (HCC) in patients with chronic HCV
infection. Aim(s): To compare the prevalence of diabetes among chronic HCV patients
in the United States (US) and China. Method(s): Prospective study of 2 cohorts of
HCV patients recruited in 1 site in the US and 2 sites in China (Beijing and Hebei)
using a standardized protocol. Diabetes was defined by the 2014 American Diabetes
Association criteria (a random plasma glucose >=200 mg/dL) or previous diagnosis of
diabetes. Result(s): 1835 patients were enrolled between 9/2011 and 4/2015. US
patients were more likely to be men (61% vs. 49%) and to be older, median age 57
vs. 53 years. US patients had higher BMI (28.3 vs. 24.5 kg/m2) and waist
circumference (WC) (40.5 vs. 33.5 in). Obesity and truncal obesity were more common
in the US than in China using race-adjusted cutoff for BMI and WC. A significantly
higher percent of US patients than Chinese patients had diabetes (21.5% vs. 10.2%)
but when stratified by liver disease severity, diabetes was more common only in US
patients without cirrhosis, 14.8% vs. 7.1%, but not in those with cirrhosis or HCC.
Older age and higher BMI were associated with increased risk for diabetes in both
cohorts. Prevalence of diabetes in US patients was higher than Chinese patients
among those aged 45-60 (22.5% vs. 10.0%, P<0.001) as well as those aged >60 (25.5%
vs. 15.6%, P=0.01). Prevalence of diabetes in US patients was also higher when
stratified by BMI (14.8% vs. 7.8% in lean, P = 0.006; 19.5% vs. 13.4% in
overweight, P=0.048; 27.8% vs. 9.7% in obese, P<0.001); or truncal obesity (24.4%
vs. 13.7%, P<0.001 in those with and 17.1% vs. 7.6%, P<0.001 in those without
truncal obesity). Multivariate analysis showed that liver disease severity, BMI and
age were significant factors associated with diabetes. Conclusion(s): This study
shows a higher prevalence of diabetes in US than in Chinese patients with chronic
HCV even after adjusting for age, BMI, and WC. A higher prevalence of diabetes in
US patients with pre-cirrhotic HCV infection may increase future risk of HCC and
management of glycometabolic abnormalities should go hand in hand with antiviral
treatment. (Table Presented).
+1&spage=1125A&pages=1125A&date=2015&title=Hepatology&atitle=Prevalence+of+diabetes
+and+associating+factors+in+patients+with+chronic+hepatitis+C+virus+%28HCV
%29+infection%3A+Comparison+of+a+Chinese+and+an+American+cohort&aulast=Rao&pid=
%3Cauthor%3ERao+H.%3BWu+E.%3BFu+S.%3BYang+M.%3BFeng+B.%3BLin+A.%3BFei+R.
%3BFontana+R.J.%3BLok+A.S.%3BWei+L.%3C%2Fauthor%3E%3CAN%3E72079846%3C%2FAN%3E%3CDT
<93>
Accession Number
72078207
Title
Voluntary exercise opposes accelerated hepatocarcinogenesis in obese, diabetic
mice by improving metabolic regulation and fatty liver disease, not via AMPK/
mTORC1.
Source
Author
Arfianti E.; Barn V.; Haigh W.G.; Yeh M.M.; Ioannou G.N.; Teoh N.C.; Farrell G.C.
Institution
(Arfianti, Barn, Teoh, Farrell) Liver Research Group, Australian National
University (ANU), Medical School at The Canberra Hospital, Canberra, ACT, Australia
(Haigh, Ioannou) Division of Gastroenterology, University of Washington, Seattle,
WA, United States
(Yeh) Division of Pathology, University of Washington, Seattle, WA, United States
Publisher
Subject Headings
*liver disease
*metabolic regulation
*ob/ob mouse
*fatty liver
*American
*liver
*exercise
mouse
liver cell
obesity
weight gain
diabetes mellitus
lipid liver level
diabetic obesity
protein expression
wild type
diseases
male
risk factor
hyperglycemia
insulin sensitivity
lipid storage
immunoblotting
gene expression
glucose tolerance
apoptosis
body weight
hyperinsulinemia
physical activity
wild type mouse
down regulation
injury
high performance liquid chromatography
mouse mutant
protein p53
diethylnitrosamine
rapamycin
cycline
DNA
sodium chloride
Drug Index Terms
protein p53; diethylnitrosamine; rapamycin; cycline; DNA; sodium chloride
Other Index Terms
*liver disease; *liver carcinogenesis; *metabolic regulation; *ob/ob mouse;
*fatty liver; *American; *liver; *exercise; mouse; liver cell; obesity; weight
gain; diabetes mellitus; lipid liver level; diabetic obesity; protein expression;
wild type; diseases; male; nonalcoholic fatty liver; risk factor; hyperglycemia;
insulin sensitivity; lipid storage; immunohistochemistry; immunoblotting; gene
expression; real time polymerase chain reaction; glucose tolerance; apoptosis; body
weight; hyperinsulinemia; physical activity; wild type mouse; down regulation;
glucose tolerance test; injury; high performance liquid chromatography; mouse
mutant
Abstract
Background Obesity and diabetes are independent risk factors for HCC associated
with non-alcoholic fatty liver disease (NAFLD), HCV and other disorders.
Diethylnitrosamine (DEN)-induced hepatocarcinogenesis is enhanced in obese,
diabetic Alms1 mutant (foz/foz) mice which develop NASH. Such accelerated
hepatocarcinogenesis is associated with hyperinsulinemia, hyperglycemia, and
Akt/mTORC1 activation, but rapamycin fails to prevent HCC. We investigated whether
exercise sufficient to slow weight gain reduces growth of dysplastic hepatocytes
and HCC development in mice genetically predisposed to obesity and diabetes.
Methods Male foz/foz and wild-type (Wt) littermates were injected with DEN (10mg/kg
i.p.) or vehicle (saline) at age 12 days. From 4wks, they were randomly assigned to
cages provided with an exercise wheel (EW) until age 12 or 24 wks, or without EW.
Dysplastic hepatocytes were identified by GST-pi immunohistochemistry (IHC),
protein expression by immunoblotting, gene expression by real-time PCR, glucose
tolerance by i.p. glucose tolerance test, hepatic lipid content using HPLC.
Result(s): foz/ foz and Wt mice provided with in-cage exercise wheels ran an
average of 4 km/day. In association with such physical activity, foz/foz weight
gain slowed to that of Wt until 12 wks; weight gain then accelerated but body
weight remained lower than non-exercising mice. At 12wks, there was a significant
reduction in GST-pi positive preneoplastic hepatocytes in exercising vs sedentary
foz/foz mice. At 24 wks, more obese foz/foz mice had HCCs than lean Wt littermates
(67% vs. 0, P<0.05). Exercise significantly reduced HCC incidence at 24 wks (to
15%). The early (12 wk) change in preneoplastic foci after exercise was associated
with lower p53 activation, less hepatocyte apoptosis (by M30-positive cells),
increased antiapoptotic Bcl-xL, and down-regulation of hepatocyte proliferation
(lower cyclin E1 and PCNA). Exercise ameliorated hepatic lipid accumulation in
foz/foz mice, improved NAFLD activity score and decreased hepatic JNK activation
(by phospho-cJun IHC). Despite improved insulin sensitivity in exercising foz/foz
mice, there was no change in Akt/mTORC1 or AMPK activation. Conclusion(s): Exercise
prevents the accelerated growth of dysplastic hepatocytes during DEN-induced
hepatocarcinogenesis that occurs with diabetes and obesity, eventually reducing HCC
in foz/foz mice. However, preventing mTORC1 activation is not the protective
mechanism. Instead, beneficial effects on fatty liver disease, JNK signalling, and
p53 response to DNA injury are likely to play important roles.
+1&spage=328A&pages=328A&date=2015&title=Hepatology&atitle=Voluntary+exercise+oppos
es+accelerated+hepatocarcinogenesis+in+obese
%2C+diabetic+mice+by+improving+metabolic+regulation+and+fatty+liver+disease
%2C+not+via+AMPK%2F+mTORC1&aulast=Arfianti&pid=%3Cauthor%3EArfianti+E.%3BBarn+V.
%3BHaigh+W.G.%3BYeh+M.M.%3BIoannou+G.N.%3BTeoh+N.C.%3BFarrell+G.C.%3C%2Fauthor%3E
<94>
Accession Number
71554996
Title
Aquaporins and glycerol metabolism in health and disease. Translational value in
liver steatosis and obesity.
Source
European Journal of Clinical Investigation. Conference: 48th Annual Scientific
Meeting of the European Society for Clinical Investigation. Utrecht Netherlands.
Conference Publication: (var.pagings). 44(SUPPL. 1) (pp 76), 2014. Date of
Author
Calamita G.; Portincasa P.; Rodriguez A.; Meacci D.; Tragni M.; Del Vecchio T.;
Marinelli R.A.; Svelto M.; Frzzuhbeck G.; Gena P.
Institution
(Calamita, Meacci, Tragni, Del Vecchio, Svelto, Gena) Department of Biosciences,
Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Bari, Italy
(Calamita, Gena) Network of Apulian Public Laboratories WAFITECH, Bari, Italy
(Portincasa) Clinica Medica A. Murri, Department Biomedical Sciences and Human
Oncology, University of Bari Aldo Moro, Bari, Italy
(Rodriguez, Frzzuhbeck) Metabolic Research Laboratory, Clinica Universidad de
Navarra, CIBERobn, Pamplona, Spain
(Marinelli) Instituto de Fisiologia Experimental, Universidad Nacional de
Rosario, Rosario, Argentina
Publisher
Subject Headings
*metabolism
*health
*fatty liver
*obesity
*society
mouse
liver
permeability
liver cell
mouse mutant
synthesis
gluconeogenesis
risk
population
diabetes mellitus
liver cirrhosis
liver disease
down regulation
insulin resistance
precursor
dyslipidemia
cell membrane
immunoblotting
hypertension
lipid storage
animal model
light scattering
glycerol blood level
defense mechanism
*glycerol
*aquaporin
protein
leptin
fatty acid
triacylglycerol
messenger RNA
glycerophosphate
Drug Index Terms
*glycerol; *aquaporin; protein; leptin; fatty acid; triacylglycerol; messenger
RNA; glycerophosphate
Other Index Terms
*metabolism; *health; *fatty liver; *obesity; *society; mouse; liver;
permeability; liver cell; mouse mutant; metabolic syndrome X; liver cell carcinoma;
nonalcoholic fatty liver; synthesis; gluconeogenesis; risk; population; diabetes
mellitus; liver cirrhosis; liver disease; down regulation; insulin resistance;
precursor; dyslipidemia; immunohistochemistry; cell membrane; immunoblotting;
hypertension; lipid storage; animal model; light scattering; glycerol blood level;
defense mechanism
Abstract
Background: The liver plays a central role in glycerol metabolism, since it is
responsible for 70-90% of the whole-body glycerol metabolism. Glycerol enters
hepatocytes via AQP9, an aquaporin channel, and is converted into glycerol-3-
phosphate, a major precursor of gluconeogenesis and a direct source for
triacylglycerol (TG) synthesis. We investigated the implication of AQP9 in Non-
Alcoholic Fatty Liver Disease (NAFLD), an emerging health problem worldwide,
characterized by increased intrahepatic influx of fatty acids, and overaccumulation
of TGs and their intermediates. NAFLD is commonly encountered with the metabolic
syndrome, a variable aggregation of visceral adiposity, hypertension, dyslipidemia,
insulin resistance or overt diabetes mellitus. NAFLD has potentials for
inflammatory and fibrotic evolution, exposing populations at risk of liver
cirrhosis, and hepatocellular carcinoma. Material(s) and Method(s): Obese leptin-
deficient (ob/ob) mice, an animal model of NAFLD, were used to correlate liver AQP9
expression, glycerol permeability and fat accumulation in hepatosteatosis.
Result(s): By qPCR, liver Aqp9 mRNA level of starved obese mice was comparable with
the corresponding control lean mice. By immunoblotting, the AQP9 protein at the
hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than
lean littermates. Results were confirmed by immunohistochemistry. By stopped-flow
light scattering, liver glycerol permeability of ob/ob mice was significantly lower
(53%) than lean mice, a finding consistent with the down-regulation of AQP9 protein
and increased level of plasma glycerol characterizing ob/ob mice. Conclusion(s):
Involvement of AQP9 in fatty liver disease is a novel finding with major
translational value. Decreased hepatic AQP9 and glycerol permeability may
constitute a defensive mechanism against enhanced glycerol accumulation. Reducing
liver AQP9 and glycerol permeability may therefore represent a novel therapeutic
approach in counteracting hepatosteatosis.
sid=OVID:embase&id=pmid:&id=doi:10.1111%2Feci.12258&issn=0014-
+1&spage=76&pages=76&date=2014&title=European+Journal+of+Clinical+Investigation&ati
tle=Aquaporins+and+glycerol+metabolism+in+health+and+disease.
+Translational+value+in+liver+steatosis+and+obesity&aulast=Calamita&pid=%3Cauthor
%3ECalamita+G.%3BPortincasa+P.%3BRodriguez+A.%3BMeacci+D.%3BTragni+M.
%3BDel+Vecchio+T.%3BMarinelli+R.A.%3BSvelto+M.%3BFrzzuhbeck+G.%3BGena+P.%3C
<95>
Accession Number
71384408
Title
JNK1 activation promotes the growth of dysplastic hepatocytes in obesity-enhanced
hepatocarcinogenesis.
Source
Hepatology International. Conference: 23rd Conference of the Asian Pacific
Association for the Study of the Liver, APASL 2014. Brisbane, QLD Australia.
Conference Publication: (var.pagings). 8(1 SUPPL. 1) (pp S239), 2014. Date of
Publication: March 2014.
Author
Arfianti E.; Lee S.S.; Heydet D.; Larter C.; Barn V.; Teoh N.C.; Farrell G.C.
Institution
(Arfianti, Lee, Heydet, Larter, Barn, Teoh, Farrell) Liver Research Group, ANU
Medical School, Canberra Hospital, ACT, Australia
Publisher
Springer New York
Subject Headings
*liver cell
*obesity
*Asian
*liver
mouse
upregulation
oxidative stress
fatty liver
diabetes mellitus
cell cycle
immunoblotting
gene
injection
wild type
insulin resistance
stress
phosphorylation
pathogenesis
liver disease
risk factor
male
cycline
protein
glutathione transferase P1
transcription factor
nuclear factor
cyclin E
Myc protein
protein kinase
stress activated protein kinase
diethylnitrosamine
protein A
sodium chloride
Drug Index Terms
cycline; protein; glutathione transferase P1; transcription factor; nuclear
factor; cyclin E; Myc protein; protein kinase; stress activated protein kinase;
diethylnitrosamine; protein A; sodium chloride
Other Index Terms
*liver cell; *obesity; *liver carcinogenesis; *Asian; *liver; mouse;
immunohistochemistry; upregulation; oxidative stress; fatty liver; diabetes
mellitus; nonalcoholic fatty liver; cell cycle; liver cell carcinoma;
immunoblotting; real time polymerase chain reaction; gene; injection; wild type;
insulin resistance; non insulin dependent diabetes mellitus; stress;
phosphorylation; pathogenesis; liver disease; risk factor; male
Abstract
Background: Obesity and type 2 diabetes are well-established risk factors for
hepatocellular carcinoma (HCC), an increasingly recognized complication of
obesity/diabetes-related non-alcoholic fatty liver disease. We previously reported
that obese and diabetic foz/foz NOD.B10 mice develop diethylnitrosamine (DEN)-
induced HCC 3 month earlier than lean mice and that Akt/mTORC1 activation is
involved in the growth of dysplastic hepatocytes [JGH 2013; 28 (Suppl):2]. The c-
Jun-N-terminal kinase (JNK) pathway, a mitogenactivated protein kinase (MAPK), is
implicated in the pathogenesis of obesity, hepatic steatosis, insulin resistance
and HCC. The aim of this study is to elucidate the role of MAPK pathways, in
particular JNK signaling, during the early (premalignant) phase of obesity-enhanced
hepatocarcinogenesis. Method(s): Male foz/foz and lean wild type littermates were
injected with DEN (10 mg/kg i.p.) at 12-15 days of age; controls were injected with
vehicle (saline). At 12 weeks post-DEN injection, dysplastic hepatocytes were
identified by glutathione S-transferase pi (GST-pi) immunohistochemistry (IHC).
Hepatic genes and proteins were examined by real-time polymerase chain reaction
(RT-PCR), immunoblotting, and immunohistochemistry (IHC). Cellular oxidative status
was assessed by GSSG/GSH level and expression of redoxsensitive transcription
factor, nuclear factor erythroid-derived 2-related factor 1 (Nrf1). Result(s): As
shown recently, DEN-treated foz/foz mice exhibited a higher number of GST-pi-
positive cells compared to respective lean mice, reflecting enhanced growth of
dysplastic hepatocytes. There was corresponding up-regulation of the cell cycle
regulators cyclin D1, cyclin E and proliferating cell nuclear antigen (PCNA).
Livers of foz/foz and lean showed equivalent increased in GSSG/GSH levels, but only
foz/foz mouse livers demonstrated induction of Nrf1, suggesting oxidative stress in
obese foz/foz mice. JNK1 activation was increased in livers of obese/diabetic
foz/foz mice during this early stage of hepatocarcinogenesis as shown by increased
phosphorylation of JNK1 and nuclear c-Jun. Despite activation of JNK1, there was
reduced expression of c-myc protein, a negative regulator of p21. Correspondingly,
p21 was increased in foz/foz mice. We also found up-regulation of TGFb in livers of
foz/foz mice, which may be associated with increased activation of JNK1.
Conclusion(s): The present study indicates that Nrf1-mediated oxidative stress
response and TGFb signalling may be involved in JNK1 activation in fatty liver
disease, which in turn contributes to enhanced growth of dysplastic hepatocytes
during the early stages of obesityaccelerated hepatocarcinogenesis.
+1&spage=S239&pages=S239&date=2014&title=Hepatology+International&atitle=JNK1+activ
ation+promotes+the+growth+of+dysplastic+hepatocytes+in+obesity-
enhanced+hepatocarcinogenesis&aulast=Arfianti&pid=%3Cauthor%3EArfianti+E.
%3BLee+S.S.%3BHeydet+D.%3BLarter+C.%3BBarn+V.%3BTeoh+N.C.%3BFarrell+G.C.%3C
<96>
Accession Number
373230806
PMID
Title
Anthropometric and biochemical characteristics of patients with nonalcoholic
fatty liver diagnosed by non-invasive diagnostic methods.
Source
Medicinski arhiv. 68(1) (pp 22-26), 2014. Date of Publication: 2014.
Author
Novakovic T.; Mekic M.; Smilic L.; Smilic T.; Inic-Kostic B.; Jovicevic L.;
Mirkovic Z.; Milinic S.
Subject Headings
article
blood
body mass
case control study
*fatty liver/di [Diagnosis]
female
glucose blood level/an [Drug Analysis]
human
male
middle aged
prospective study
waist circumference
cholesterol
insulin
Drug Index Terms
cholesterol; insulin
Other Index Terms
article; blood; body mass; case control study; *fatty liver / *diagnosis; female;
glucose blood level / drug analysis; human; male; middle aged; nonalcoholic fatty
liver; prospective study; waist circumference
Abstract
Non-alcoholic (NAFLD) encompasses a spectrum of disease states, from steatosis
(fatty liver) to non-alcoholic steatohepatitis (also called NASH steatosis with
inflammatory changes) followed by progression to fibrosis and cirrhosis and
hepatocellular carcinoma Excess liver fat is believed to be a manifestation of the
metabolic syndrome and not surprisingly NASH is associated with obesity, insulin
resistance, dyslipidemia and type 2 diabetes in humans. Is to establish
anthropometric and biochemical specificities in patients with non-alcoholic
steatohepatitis diagnosed with non-invasive diagnostic methods. Study enrolled 170
participants, 130 with NASH steatosis. The non-alcoholic group (control), consisted
of 40 normal weight patients without metabolic syndrome. Alcohol intake was
estimated with established protocol. Routine biochemistry analysis were performed
by standard laboratory procedures; serum levels of serum levels of fasting
cholesterol and triglycerides, fasting glucose and insulin, insulin resistance
estimated by HOMA index (Homeostasis model assessment), biochemistry tests and a
liver ultrasound examination. In study participants group, patients were more obese
comparing with controls p < 0.01, waist line extent also was of greater statistical
significance in the non-alcoholic group fatty liver (p < 0, 01). Comparing
biochemical parameter values, significant statistical deference has been noted in
glaucosis and insulin levels, total cholesterol and gama-glutamil transferase
levels, between groups (p < 0.01). Fasting glucose and insulin levels, HOMA-IR were
significantly greater in study cohort group patients, as was significantly positive
correlation between BMI and waist line extent. Patients with non-alcoholic fatty
liver are excessively obese, have greater waist line extent, consequently insulin
resistance and impaired glucose metabolism, insulin resistance, dyslipidemia, risk
factors known to be associated with the development of cardiovascular disease.
sid=OVID:embase&id=pmid:24783906&id=doi:10.5455%2Fmedarh.2014.68.22-26&issn=0350-
26&date=2014&title=Medicinski+arhiv&atitle=Anthropometric+and+biochemical+character
istics+of+patients+with+nonalcoholic+fatty+liver+diagnosed+by+non-
invasive+diagnostic+methods&aulast=Novakovic&pid=%3Cauthor%3ENovakovic+T.
%3BMekic+M.%3BSmilic+L.%3BSmilic+T.%3BInic-Kostic+B.%3BJovicevic+L.%3BMirkovic+Z.
%3BMilinic+S.%3C%2Fauthor%3E%3CAN%3E373230806%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<97>
Accession Number
372572221
Title
Nonalcoholic liver disease and non-alcoholic steato hepatitis: A review in eyes
of a histopathologist of West Bengal, India.
Source
Annals of Tropical Medicine and Public Health. 6(4) (pp 393-400), 2013. Date of
Publication: July-August 2013.
Author
Bhattacharya P.K.; Bhattacharya U.; Bhattacharya S.; Barman D.R.; Bhattacharya
R.; Mukherjee O.; Mukherjee D.; De A.; Sarkar S.; Haldar S.
Institution
(Bhattacharya, Bhattacharya, De, Sarkar, Haldar) Department of Pathology,
Calcutta School of Tropical Medicine, West-Bengal, India
(Bhattacharya, Bhattacharya, Bhattacharya, Bhattacharya, Sarkar, Haldar)
Purbapalli, Sodepur, 24 Parganas (north) West Bengal, West-Bengal, India
(Mukherjee, Mukherjee, Mukherjee, Sarkar, Haldar) Swamiji Nagar, South Habra,
North 24 Parganas, Kolkata, West Bengal, India
(Barman, Sarkar, Haldar) Department of Oncopathology, Medical College Kolkata,
Kolkata, West Bengal, India
Publisher
Medknow Publications and Media Pvt. Ltd (B9, Kanara Business Centre, off Link
Road, Ghatkopar (E), Mumbai 400 075, India)
Subject Headings
Australia
author
body mass
body weight
China
city
death
diagnostic imaging
disease association
disease course
disorders of mitochondrial functions
epidemic
ethnicity
Europe
familial disease
fast food
feeding behavior
follow up
food intake
genetic disorder
hepatitis
histopathology
human
India
insulin resistance
lipodystrophy
liver biopsy
liver cirrhosis/co [Complication]
liver graft
medical history
medical technology
needle biopsy
nuclear magnetic resonance imaging
obesity
phenotype
positron emission tomography
protein blood level
radiologist
review
rural area
scoring system
United States
adiponectin/ec [Endogenous Compound]
fetuin A/ec [Endogenous Compound]
leptin/ec [Endogenous Compound]
liver enzyme/ec [Endogenous Compound]
tumor necrosis factor alpha/ec [Endogenous Compound]
NasH scoring system
Candidate Terms
nash scoring system [other term]
Drug Index Terms
adiponectin / endogenous compound; C reactive protein / endogenous compound;
fetuin A / endogenous compound; leptin / endogenous compound; liver enzyme /
endogenous compound; tumor necrosis factor alpha / endogenous compound
Other Index Terms
Australia; author; body mass; body weight; China; city; death; diagnostic
imaging; disease association; disease course; disorders of mitochondrial functions;
epidemic; ethnicity; Europe; familial disease; fast food; feeding behavior; follow
up; food intake; genetic disorder; hepatitis; histopathology; human; India; insulin
resistance; lifestyle modification; lipodystrophy; liver biopsy; liver cell
carcinoma; liver cirrhosis / complication; liver graft; medical history; medical
technology; needle biopsy; non insulin dependent diabetes mellitus; *nonalcoholic
fatty liver / *diagnosis; nuclear magnetic resonance imaging; obesity; phenotype;
positron emission tomography; protein blood level; radiologist; review; rural area;
scoring system; United States
Abstract
NAFLD characterized by steatosis, when NASH by steatosis, lobular inflammation or
steatosis with fibrosis. NAFLD increasingly recognized today as hepatic
manifestation of systemic 'metabolic complex also in India and in province like
West Bengal with BMI greater than equal 30kg/m2 , 67% of overweight patients in
which BMI greater than or equal to 25 kg/m2 and even in 25% normal weight
population or with uncontrolled type 2- NIDDM. NAFLD/NASH today one of most common
liver diseases in USA, Australia, Europe, Asian countries like china, Dallas,
India, and West Bengal with emerging epidemic of obesity due to DM, consumption of
fast food and rich food habits in people of industrialized cities and towns even in
rural villages of West Bengal. NASH a progressive form of the disease finally leads
to cryptogenic cirrhosis of liver even HepatoCellular Carcinoma requires liver
transplant for cure. In most cases of NASH, Insulin resistance is found. The
responsible gene is fetuin-A (FetA), ethnicity, Familial clustering in first degree
relatives (20% of NASH). Natural history of NAFLD variable, although most patients
experience an indolent course, some others progress to cirrhosis and liver related
death. Paired liver biopsy data of predominantly NASH patients shows that over a
follow up period of 2-5 years 18% - 29% patients improved with life style
modification and treatment, 34% to 53% remain stable and 26% to 37% develop
Cirrohosis and 9% of Cirrohosis from NASH within short time, The two hit hypothesis
is widely accepted theory to explain progression of NAFLD from benign steatosis
towards NASH. Diagnosis of NASH is challenging before clinicians, Radiologists by
USG, with fibroscan devices, MRI, PET scan unless live needle biopsy is done and
final diagnosis of NASH remains in clinical knowledge of combined Hepatologists and
Hispatothologists. Liver enzymes, several biomarkers for NASH availble like TNF-
alpha, Adiponectin- TNF/adiponectin ratio, serum leptin, C reactive protein.
sid=OVID:embase&id=pmid:&id=doi:10.4103%2F1755-6783.127769&issn=1755-
400&date=2013&title=Annals+of+Tropical+Medicine+and+Public+Health&atitle=Nonalcohol
ic+liver+disease+and+non-alcoholic+steato+hepatitis
%3A+A+review+in+eyes+of+a+histopathologist+of+West+Bengal
%2C+India&aulast=Bhattacharya&pid=%3Cauthor%3EBhattacharya+P.K.%3BBhattacharya+U.
%3BBhattacharya+S.%3BBarman+D.R.%3BBhattacharya+R.%3BMukherjee+O.%3BMukherjee+D.
%3BDe+A.%3BSarkar+S.%3BHaldar+S.%3C%2Fauthor%3E%3CAN%3E372572221%3C%2FAN%3E%3CDT
<98>
Accession Number
52762816
Title
Long-term Branched Chain Amino Acid Supplementation Ameliorates
Diethylnitrosamine-induced Liver Glutathione S-transferase-p Positivity in Zucker
Fatty Rats.
Source
Journal of Clinical and Experimental Hepatology. 3(3) (pp 192-197), 2013. Date of
Publication: September 2013.
Author
Ishizaki S.; Nishiyama M.; Hagiwara A.
Institution
(Ishizaki, Nishiyama, Hagiwara) Exploratory Research Laboratories, Research
Center, Ajinomoto Pharmaceuticals Co.Ltd., Kawasaki, Japan
Publisher
Elsevier
Subject Headings
animal experiment
animal model
animal tissue
antineoplastic activity
article
controlled study
*diet supplementation
drug mechanism
enzyme phosphorylation
in vivo study
insulin resistance
liver adenoma
male
nonhuman
obesity
priority journal
protein expression
protein localization
rat
Zucker diabetic fatty rat
*amino acid/pd [Pharmacology]
cyclin D1/ec [Endogenous Compound]
*diethylnitrosamine
*glutathione transferase/ec [Endogenous Compound]
protein bcl 2/ec [Endogenous Compound]
protein p21/ec [Endogenous Compound]
thymidine kinase/ec [Endogenous Compound]
unclassified drug
*long term branched chain amino acid/pd [Pharmacology]
Candidate Terms
*long term branched chain amino acid / *pharmacology [drug term]
Drug Index Terms
*amino acid / *pharmacology; cyclin D1 / endogenous compound;
*diethylnitrosamine; *glutathione transferase / *endogenous compound; protein bcl 2
/ endogenous compound; protein p21 / endogenous compound; thymidine kinase /
endogenous compound; unclassified drug
Other Index Terms
animal experiment; animal model; animal tissue; antineoplastic activity; article;
controlled study; *diet supplementation; drug mechanism; enzyme phosphorylation; in
vivo study; insulin resistance; liver adenoma; *liver carcinogenesis; liver cell
carcinoma; male; nonhuman; obesity; priority journal; protein expression; protein
localization; rat; Zucker diabetic fatty rat
Abstract
Background: Obesity increases the risk of fatty liver disease and liver cancer.
There are several models of obesity-associated hepatocellular carcinoma, but tumor
development in these models is slow. Material(s) and Method(s): We investigated
Zucker fatty rats, a model of obesity and insulin resistance, to discover if
diethylnitrosamine (DEN), a potent liver carcinogen, might enhance liver
carcinogenesis. We also investigated the effect of branched chain amino acids
(BCAA) against the development of liver cancer. Result(s): Incidence and number of
hepatocellular carcinomas and adenomas were significantly greater in DEN-treated
Zucker fatty rats than in DEN-treated lean rats. All treated Zucker fatty rats
developed hepatocellular carcinoma within 16 weeks. Long-term BCAA supplementation
significantly reduced expression of CyclinD1, PCNA, thymidine kinase, Bcl-2, and
GST-p and increased expression of p21 in the liver. Furthermore, BCAA treatment
significantly reduced the area of GST-p positive foci. Conclusion(s): Long-term
BCAA treatment may induces cell cycle arrest and apoptotic induction, thus
suppressing pre-neoplastic lesions. © 2013 INASL.
sid=OVID:embase&id=pmid:&id=doi:10.1016%2Fj.jceh.2013.08.008&issn=0973-
197&date=2013&title=Journal+of+Clinical+and+Experimental+Hepatology&atitle=Long-
term+Branched+Chain+Amino+Acid+Supplementation+Ameliorates+Diethylnitrosamine-
induced+Liver+Glutathione+S-transferase-
p+Positivity+in+Zucker+Fatty+Rats&aulast=Ishizaki&pid=%3Cauthor%3EIshizaki+S.
%3BNishiyama+M.%3BHagiwara+A.%3C%2Fauthor%3E%3CAN%3E52762816%3C%2FAN%3E%3CDT
<99>
Accession Number
72263072
Title
Incretins in NASH/NAFLD: Pathophysiological implications.
Source
United European Gastroenterology Journal. Conference: 21st United European
Gastroenterology Week. Berlin Germany. Conference Publication: (var.pagings). 1(1
SUPPL. 1) (pp A99), 2013. Date of Publication: October 2013.
Author
Meyer-Gerspach A.C.; Bernsmeier C.; Blaser L.; Jeker L.; Steinert R.E.; Heim
M.H.; Beglinger C.
Institution
(Meyer-Gerspach, Bernsmeier, Blaser, Jeker, Steinert, Heim, Beglinger) Department
of Biomedicine, Division of Gastroenterology, University Hospital Basel, Basel,
Switzerland
Publisher
Subject Headings
*European
*gastroenterology
human
secretion (process)
patient
insulin resistance
weight control
fatty liver
blood level
liver cirrhosis
obesity
disease course
risk
mouse
experimental study
liver failure
pathogenesis
glucose homeostasis
glucagon release
insulin release
diabetic patient
diet restriction
assay
glucose intake
homeostasis
model
liver disease
hypothesis
oral glucose tolerance test
*glucagon like peptide 1
*gastric inhibitory polypeptide
*incretin
insulin
glucose
glucagon like peptide 1 receptor
glucagon like peptide 1 receptor agonist
peptide hormone
gastrointestinal polypeptide
glucagon
Drug Index Terms
*glucagon like peptide 1; *gastric inhibitory polypeptide; *incretin; insulin;
glucose; glucagon like peptide 1 receptor; glucagon like peptide 1 receptor
agonist; peptide hormone; gastrointestinal polypeptide; glucagon
Other Index Terms
*European; *gastroenterology; human; secretion (process); patient; insulin
resistance; weight control; glucose tolerance test; nonalcoholic fatty liver; fatty
liver; blood level; liver cirrhosis; obesity; disease course; liver cell carcinoma;
risk; mouse; experimental study; liver failure; pathogenesis; glucose homeostasis;
glucagon release; insulin release; chronic liver disease; diabetic patient; diet
restriction; assay; glucose intake; homeostasis; model; liver disease; non insulin
dependent diabetes mellitus; hypothesis; oral glucose tolerance test
Abstract
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is one of the most
frequent chronic liver diseases in Western countries. Non-alcoholic steatohepatitis
(NASH) is a subgroup of NAFLD and carries the risk of disease progression and
complications such as cirrhosis, liver failure or hepatocellular carcinoma. Both
NASH and NAFLD are associated with obesity, insulin resistance, and type 2 diabetes
mellitus (T2DM). Incretins, such as glucose-dependent insulinotropic polypeptide
(GIP) and glucagon- like peptide-1 (GLP-1), are gastrointestinal peptide hormones
regulating postprandial insulin release from the pancreatic beta-cell. GLP-1
agonism has been approved as treatment strategy in T2DM using GLP-1 agonists. The
role of incretins in NAFLD is insufficiently understood. Experimental studies in
mice suggest improvement of hepatic steatosis by GLP-1 agonism probably through a
mechanism involving hepatic GLP-1 receptors. The aims of this study were to
determine the concentrations of incretins (GLP-1 and GIP), glucose and insulin
after a standard glucose tolerance test in NAFLD patients. The results were
compared to a cohort of healthy controls. AIMS&METHODS: The study included a cohort
of 52 non-diabetic patients with NAFLD and 50 matched, healthy, normal-weight,
controls. A standardized oral 75 g glucose tolerance test (oGTT) was performed.
Plasma levels of GLP-1, GIP, insulin, glucose and glucagon were measured
sequentially for 120 minutes before and after the glucose administration using
specific assay systems. Insulin resistance was estimated as the homeostasis model
of assessment for insulin resistance (HOMA-IR) index. RESULT(S): Based on the HOMA-
IR, NAFLD patients were insulin resistant (p < 0.0001) with increased fasting and
postprandial insulin concentrations; the glucose lowering effect was, however,
diminished. Glucose induced GLP-1 secretion was markedly decreased in patients with
fatty liver disease compared to normal weight controls (p < 0.001) with no
difference in GLP-1 secretion between NAFLD and NASH subgroups. In contrast, GIP
secretion was unchanged in NAFLD/NASH compared to controls. Glucagon secretion was
significantly higher in NAFLD (p < 0.001) compared to controls. CONCLUSION(S):
Patients with NAFLD are insulin resistant and show an impaired glucose homeostasis.
Incretins show a dissociated response to oral glucose: GLP-1 secretion is impaired
in both NAFLD and NASH subgroups, but GIP release is unchanged. Our data support
the hypothesis that dysregulation of GLP-1 secretion is involved in the
pathogenesis of human NAFLD. GLP- 1 analogues might therefore be beneficial in the
treatment of NAFLD.
+1&spage=A99&pages=A99&date=2013&title=United+European+Gastroenterology+Journal&ati
tle=Incretins+in+NASH%2FNAFLD%3A+Pathophysiological+implications&aulast=Meyer-
Gerspach&pid=%3Cauthor%3EMeyer-Gerspach+A.C.%3BBernsmeier+C.%3BBlaser+L.%3BJeker+L.
%3BSteinert+R.E.%3BHeim+M.H.%3BBeglinger+C.%3C%2Fauthor%3E%3CAN%3E72263072%3C%2FAN
%3E%3CDT%3EConference+Abstract%3C%2FDT%3E
<100>
Accession Number
71055557
Title
Hepatic pten deficiency triggers steatosis development but improves glucose
tolerance by inhibiting hepatic gluconeogenesis and inducing muscle insulin
hypersensitivity.
Source
Journal of Hepatology. Conference: 48th Annual Meeting of the European
Association for the Study of the Liver, International Liver Congress 2013.
Amsterdam Netherlands. Conference Publication: (var.pagings). 58(SUPPL. 1) (pp
S519-S520), 2013. Date of Publication: April 2013.
Author
Peyrou M.; Bourgoin L.; Maeder C.; Caillon A.; Rohner-Jeanrenaud F.; Foti M.
Institution
(Peyrou, Bourgoin, Maeder, Foti) Cell Physiology and Metabolism, Switzerland
(Caillon, Rohner-Jeanrenaud) Department of Internal Medicine, Faculty of
Medicine, University of Geneva, Geneva, Switzerland
Publisher
Elsevier
Subject Headings
*liver
*glucose tolerance
*gluconeogenesis
*muscle
*insulin allergy
*steatosis
mouse
phosphorylation
clamp
skeletal muscle
muscle tissue
human
mouse mutant
blood level
rat
knockout mouse
hepatomegaly
energy expenditure
thermoregulation
fat mass
body weight
locomotion
glucose utilization
glucose infusion
fatty liver
dyslipidemia
glucose blood level
ex vivo study
insulin sensitivity
infusion rate
neoplasm
insulin
insulin receptor
phosphatase
pyruvic acid
glucose
enzyme
glycolytic enzyme
phosphatidylinositide
Drug Index Terms
insulin; insulin receptor; phosphatase; pyruvic acid; glucose; enzyme; glycolytic
enzyme; phosphatidylinositide
Other Index Terms
*liver; *glucose tolerance; *gluconeogenesis; *muscle; *insulin allergy;
*steatosis; mouse; phosphorylation; clamp; skeletal muscle; muscle tissue; human;
mouse mutant; blood level; rat; knockout mouse; hepatomegaly; energy expenditure;
thermoregulation; fat mass; liver cell carcinoma; body weight; locomotion; glucose
utilization; glucose infusion; fatty liver; dyslipidemia; glucose blood level; ex
vivo study; insulin sensitivity; infusion rate; neoplasm
Abstract
Background and Aims: PTEN is a tumour suppressor with a phosphoinositide
phosphatase activity antagonizing PI3K signaling. Hepatic PTEN deficiency in mice
induces steatosis, inflammation/fibrosis and hepatocellular carcinoma. Supporting a
role for PTEN in steatosis development, we previously reported PTEN downregulation
in steatotic livers of obese rats and humans. Interestingly, although liver-
specific PTEN knockout mice develop steatosis/inflammation/fibrosis, they
paradoxically exhibit an improved glucose tolerance. This study aims at
understanding the mechanisms by which PTEN deficiency improves glucose tolerance,
while promoting steatosis/inflammation/fibrosis. Material(s) and Method(s): 4-month
old AlbCre/PTENfx/fx mice (PTENKO) and PTENfx/fx mice (CTL) were phenotypically
characterized and subjected to glucose and pyruvate tolerance tests, as well as
euglycemic hyperinsulinemic clamps. Ex-vivo liver and muscle tissues from mice
stimulated or not with insulin were analysed. Result(s): Liver-specific deletion of
PTEN did not modulate body weight, ratio of lean vs total fat mass, food/water
intake, locomotor activity, thermoregulation and energy expenditure in mice, but as
previously described, it induced hepatomegaly and a marked hepatic steatosis. In
the fed state, PTENKO mice displayed increased ALT/AST serum levels, dyslipidemia,
but normal glycemia. Interestingly, PTENKO mice exhibited an improved glucose
tolerance that was due in part to a constitutive inhibition of gluconeogenesis.
Impaired gluconeogenesis was associated with an increased basal Akt
phosphorylation, but an inhibition of insulin receptor and IRS1
expressions/activities and hepatic refractoriness to further insulin signalling. In
addition, expression of glycolytic enzymes was increased, whereas that of PEPCK, a
rate-limiting enzyme in gluconeogenesis was downregulated. Surprisingly, PTENKO
mice exhibited a significant increase in skeletal muscle insulin sensitivity.
Indeed, analyses of insulin signaling in exvivo muscle tissues revealed increased
phosphorylation of the insulin receptor, IRS1 and Akt in insulin-stimulated PTENKO
mice. Confirming these data, euglycemic hyperinsulinemic clamps demonstrated a
marked increase in the glucose infusion rate and the glucose utilization index in
all types of skeletal muscles from PTENKO compared to CTL mice. Conclusion(s):
Although liver-specific PTEN deficiency in mice triggers
steatosis/inflammation/fibrosis, glucose tolerance is improved through inhibition
of hepatic gluconeogenesis and through a liver to muscle crosstalk, promoting
muscle insulin hypersensitivity.
8278&isbn=&volume=58&issue=SUPPL.+1&spage=S519&pages=S519-
S520&date=2013&title=Journal+of+Hepatology&atitle=Hepatic+pten+deficiency+triggers+
steatosis+development+but+improves+glucose+tolerance+by+inhibiting+hepatic+gluconeo
genesis+and+inducing+muscle+insulin+hypersensitivity&aulast=Peyrou&pid=%3Cauthor
%3EPeyrou+M.%3BBourgoin+L.%3BMaeder+C.%3BCaillon+A.%3BRohner-Jeanrenaud+F.
%3BFoti+M.%3C%2Fauthor%3E%3CAN%3E71055557%3C%2FAN%3E%3CDT%3EConference+Abstract%3C
%2FDT%3E
<101>
Accession Number
71226771
Title
Enhanced growth of dysplastic hepatocytes is associated with activation of
Akt/mTORC1 pathway in a murine model of hyperphagic-obesity.
Source
Journal of Gastroenterology and Hepatology. Conference: Australian
Gastroenterology Week 2013. Melbourne, VIC Australia. Conference Publication:
(var.pagings). 28(SUPPL. 2) (pp 3-4), 2013. Date of Publication: October 2013.
Author
Arfianti E.; Lee S.S.; Heydet D.; Larter C.; Barn V.; Teoh N.C.; Farrell G.C.
Institution
(Arfianti, Lee, Heydet, Larter, Barn, Teoh, Farrell) Liver Research Group, ANU
Medical School, Canberra Hospital, ACT, Australia
Publisher
Blackwell Publishing
Subject Headings
*liver cell
*murine model
*obesity
*gastroenterology
mouse
mouse mutant
liver
phosphorylation
hyperglycemia
protein expression
hyperinsulinemia
assay
serum
immunoblotting
diabetic obesity
injection
cell viability
male
tumor growth
cell survival
cell proliferation
protein synthesis
diabetes mellitus
raptor
cell cycle
upregulation
nutrient
apoptosis
inflammation
cell culture
down regulation
rapamycin
cycline
glutathione transferase P1
insulin
diethylnitrosamine
protein kinase
mammalian target of rapamycin
marker
adipocytokine
sodium chloride
Drug Index Terms
rapamycin; cycline; glutathione transferase P1; insulin; diethylnitrosamine;
protein kinase; mammalian target of rapamycin; marker; adipocytokine; sodium
chloride
Other Index Terms
*liver cell; *murine model; *obesity; *gastroenterology; mouse; mouse mutant;
liver; phosphorylation; hyperglycemia; protein expression; hyperinsulinemia; liver
carcinogenesis; assay; serum; liver cell carcinoma; immunoblotting;
immunohistochemistry; diabetic obesity; injection; cell viability; male; non
insulin dependent diabetes mellitus; tumor growth; cell survival; cell
proliferation; protein synthesis; diabetes mellitus; raptor; nonalcoholic fatty
liver; cell cycle; upregulation; nutrient; apoptosis; inflammation; cell culture;
down regulation
Abstract
Background: Obesity and type 2 diabetes both promote the development of
hepatocellular carcinoma (HCC), which is an increasingly recognized complication of
obesity/diabetes-related non-alcoholic fatty liver disease. We recently reported
early onset of diethylnitrosamine (DEN)-induced HCC in obese and diabetic foz/foz
NOD.B10 mice which was associated with hyperinsulinemia, hyperglycemia and
perturbed serum adipokine levels, rather than inflammation [JGH 2011; 26
(Suppl):6]. The mammalian target of rapamycin (mTOR), a nutrient-sensitive protein
kinase, is abberantly activated in up to 50% of HCC cases. In the present study, we
investigate the role of Akt/mTOR signalling pathways during the early
(premalignant) stage of hepatocarcinogenesis. Methods Male foz/foz and non-obese
heterozygous (foz+/-) littermates were injected with DEN (10 mg/kg i.p.) at 12-15
days of age; controls were injected with vehicle (saline). At 12 weeks post-DEN
injection, dysplastic hepatocytes were identified by glutathione S-transferase pi
(GST-pi) immunohistochemistry (IHC). Protein expression of Akt/mTOR signalling
intermediates in liver lysates were analysed by immunoblotting and IHC.We also
determined the growth inhibitory effect of rapamycin on primary HCC cell culture
using cells derived from foz/foz mice using MTT assays. Result(s): DEN-treated
foz/foz mice exhibited a higher number of GST-pipositive cells compared to
respective lean mice (3.7 +/- 0.68% vs. 1.6 +/- 0.20 %, P < 0.05), reflecting
enhanced growth of dysplastic hepatocytes. DEN increased proliferative and
apoptosis markers in obese mice, corresponding to the up-regulation of positive
cell cycle regulators (cyclins D1, E) and pro-apoptotic Bax, respectively.
Interestingly, Akt phosphorylation, an important mediator of insulin signalling,
was enhanced in livers from DEN-injected obese mice. Further, downstream inhibitors
of mTOR complex 1 (mTORC1), TSC2 and PRAS40, were phosphorylated in DENinjected
foz/foz liver, resulting in de-repression of mTOR inhibition to allow mTORC1
activation. Likewise, both Raptor and mTOR phosphorylation were increased in obese
mice, indicative of mTORC1 activation. The functional relevance of this for control
of hepatocyte growth was evident by enhanced phosphorylation of both 4E-BP1 and
elF-4B, which are the key downstream targets of mTOR that control growth, protein
synthesis, cell proliferation and cell survival. In order to gain further evidence
for the role of mTOR signaling in tumor cell growth, we treated primary HCC cells
derived from DEN-injected foz/foz mice with rapamycin. MTT assay revealed that
rapamycin markedly decreased HCC cell viability after 48 hours treatment in dose-
dependent manner vs control. Further, rapamycin reduced levels of phospho-mTOR,
phospho-4E-BP1 and phospho-p70S6K (Figure Presented) protein expressions, leading
to down-regulation of cyclin D1 and cyclin E. These results further support the
crucial role of mTORC1 pathway in hepatocyte growth and proliferation.
Conclusion(s): Enhanced growth of dysplastic hepatocytes in the early stages of
obesity-accelerated hepatocarcinogenesis is associated with hyperinsulinemia and
hyperglycemia that induces and activates the Akt/ mTOR pathway to promote
hepatocyte growth in obese-diabetic mice with HCC.
sid=OVID:embase&id=pmid:&id=doi:10.1111%2Fjgh.12365&issn=0815-
9319&isbn=&volume=28&issue=SUPPL.+2&spage=3&pages=3-
4&date=2013&title=Journal+of+Gastroenterology+and+Hepatology&atitle=Enhanced+growth
+of+dysplastic+hepatocytes+is+associated+with+activation+of+Akt
%2FmTORC1+pathway+in+a+murine+model+of+hyperphagic-obesity&aulast=Arfianti&pid=
%3Cauthor%3EArfianti+E.%3BLee+S.S.%3BHeydet+D.%3BLarter+C.%3BBarn+V.%3BTeoh+N.C.
%3BFarrell+G.C.%3C%2Fauthor%3E%3CAN%3E71226771%3C%2FAN%3E%3CDT
<102>
Accession Number
361027212
PMID
Title
Nonalcoholic fatty liver in Asia: Firmly entrenched and rapidly gaining ground.
Source
Journal of Gastroenterology and Hepatology (Australia). 26(SUPPL. 1) (pp 163-
172), 2011. Date of Publication: January 2011.
Author
Chitturi S.; Wong V.W.-S.; Farrell G.
Institution
(Chitturi, Farrell) Gastroenterology and Hepatology Unit, The Canberra Hospital,
Australian Capital Territory, Canberra, Australia
(Wong) The Department of Medicine and Therapeutics, The Chinese University of
Hong Kong, Hong Kong SAR, Hong Kong
Publisher
Blackwell Publishing
Subject Headings
anthropometry
Asia
body mass
body weight
childhood disease
diabetes mellitus
diet therapy
disease course
disease severity
DNA polymorphism
elastography
exercise
hepatitis B
hepatitis C
hepatography
human
impaired glucose tolerance
insulin resistance
liver cirrhosis
liver fibrosis
medical history
non invasive procedure
*nonalcoholic fatty liver/th [Therapy]
obesity
pathogenesis
patient assessment
patient education
prevalence
priority journal
review
adipocytokine receptor/ec [Endogenous Compound]
apolipoprotein C3/ec [Endogenous Compound]
cytokeratin 18/ec [Endogenous Compound]
hyaluronic acid/ec [Endogenous Compound]
Drug Index Terms
adipocytokine receptor / endogenous compound; apolipoprotein C3 / endogenous
compound; cytokeratin 18 / endogenous compound; glucose / endogenous compound;
hyaluronic acid / endogenous compound
Other Index Terms
anthropometry; Asia; body mass; body weight; childhood disease; diabetes
mellitus; diet therapy; disease course; disease severity; DNA polymorphism;
elastography; exercise; glucose tolerance test; hepatitis B; hepatitis C;
hepatography; human; impaired glucose tolerance; insulin resistance; lifestyle
modification; liver cell carcinoma; liver cirrhosis; liver fibrosis; medical
history; metabolic syndrome X; non invasive procedure; *nonalcoholic fatty liver /
*epidemiology / *therapy; obesity; pathogenesis; patient assessment; patient
education; prevalence; priority journal; review
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming an important chronic liver
disorder in Asia. Prevalence figures show regional variations but at least 10% of
the general population in Asia have fatty liver. Fatty liver can develop with
relatively small changes in weight (2-3 kg), often with increasing central
adiposity. The metabolic syndrome may precede or follow NAFLD. Overt diabetes is
present in one-third of cases but when oral glucose tolerance tests are performed,
a further third of individuals have impaired glucose tolerance or diabetes. Natural
history data are still scarce but cases of advanced hepatic fibrosis and
hepatocellular carcinoma are now regularly reported. Many cases of cryptogenic
cirrhosis are also attributable to NAFLD. Histological progression has been
demonstrated for patients with NASH as well as for those with hepatic steatosis
alone. Genetic factors may in part contribute to the rise in NAFLD. Polymorphisms
within apolipoprotein C3 (APOC3) gene have been linked to NAFLD in lean Indian men.
Although a number of other polymorphisms involving genes controlling adipose
distribution, insulin signalling, adipokine responses and hepatic fibrosis have
been reported, these studies have been underpowered. Transient elastography could
help in detecting and monitoring hepatic fibrosis but further refinements in
technique are necessary for obese individuals. Of the biomarkers, hyaluronic acid
and cytokeratin-18 fragment testing show promise as markers of hepatic fibrosis and
NASH, respectively. Lifestyle alterations including dietary changes and increased
physical activity remain the cornerstone of management. Attention should be paid to
prevention through public education of campaigns addressing the increase in both
adult and childhood obesity. © 2011 Journal of Gastroenterology and Hepatology
Foundation and Blackwell Publishing Asia Pty Ltd.
sid=OVID:embase&id=pmid:21199528&id=doi:10.1111%2Fj.1440-
1746.2010.06548.x&issn=0815-9319&isbn=&volume=26&issue=SUPPL.
+1&spage=163&pages=163-
%29&atitle=Nonalcoholic+fatty+liver+in+Asia
%3A+Firmly+entrenched+and+rapidly+gaining+ground&aulast=Chitturi&pid=%3Cauthor
%3EChitturi+S.%3BWong+V.W.-S.%3BFarrell+G.%3C%2Fauthor%3E%3CAN%3E361027212%3C%2FAN
%3E%3CDT%3EReview%3C%2FDT%3E
<103>
Accession Number
70687684
Title
Diet-induced non-alcoholic steatohepatitis and hepatocellular carcinoma in
chromosome substitution strains of mice.
Source
Cancer Research. Conference: 102nd Annual Meeting of the American Association for
Cancer Research, AACR 2011. Orlando, FL United States. Conference Publication:
(var.pagings). 71(8 SUPPL. 1) (no pagination), 2011. Date of Publication: 15 Apr
2011.
Author
Hill-Baskin A.E.; Spiezio S.H.; DeSantis D.; Croniger C.; Lambris J.D.; Nadeau
J.H.; Berger N.A.
Institution
(Hill-Baskin) Department of Genetics, Case Western Reserve University, School of
Medicine, Cleveland, OH, United States
(Spiezio, Nadeau) Institute for Systems Biology, Seattle, WA, United States
(DeSantis, Croniger) Department of Nutrition, Case Western Reserve University,
School of Medicine, Cleveland, OH, United States
(Lambris) Department of Pathology and Laboratory Medicine, University of
Pennsylvania, Philadelphia, PA, United States
(Berger) Case Center for Transdisciplinary Research on Energetics and Cancer,
Case Comprehensive Cancer Center, Case Western Reserve University School of
Medicine, Cleveland, OH, United States
Publisher
Subject Headings
*diet
*mouse
*chromosome substitution strain
*cancer research
obesity
male
metabolic disorder
liver
neoplasm
human
inbred strain
liver disease
genotype environment interaction
chromosome
donor
parent
risk factor
tumor
long term exposure
mouse strain
low fat diet
lipid diet
liver cancer
diseases
insulin resistance
model
gene
pathogenesis
risk
patient
hepatitis C
alcoholism
animal model
liver cell
messenger RNA
lipid
aflatoxin
biological product
RNA
Drug Index Terms
messenger RNA; lipid; aflatoxin; biological product; RNA
Other Index Terms
*diet; *mouse; *chromosome substitution strain; *liver cell carcinoma;
*nonalcoholic fatty liver; *cancer research; obesity; male; metabolic disorder;
liver; neoplasm; human; inbred strain; liver disease; genotype environment
interaction; chromosome; donor; parent; risk factor; tumor; long term exposure;
mouse strain; low fat diet; lipid diet; liver cancer; diseases; insulin resistance;
model; gene; pathogenesis; risk; patient; hepatitis C; alcoholism; animal model;
liver cell
Abstract
Hepatocellular Carcinoma (HCC) is the 5th most common cancer worldwide, with
increased risk occurring in patients with hepatitis C and B, alcoholism, aflatoxin,
and metabolic diseases. Animal models that target liver cells with chemical,
physical or biological agents are useful for understanding molecular pathways, but
do not capture the natural development of liver cancer through gene-environment
interactions. By contrast, several inbred strains of mice have been used to study
these interactions in diet-induced metabolic diseases. In particular, C57BL/6J (B6)
inbred mice are susceptible to diet-induced obesity, lipid disorders and insulin
resistance, whereas A/J mice produce no signs of these diet-induced conditions. In
these inbred models, the action of many genes and gene-environment interactions
more closely reflect the usual features in non-alcoholic steatohepatitis (NASH) and
HCC pathogenesis. Previous studies showed that B6 males are susceptible to diet-
induced obesity and non-alcoholic fatty liver disease (NAFLD). We therefore
examined the long-term effects of a high fat (HF) diet versus a low fat (LF) diet
in males from two inbred strains A/J and B6 to determine whether conditions
associated with risk factors ultimately transition to HCC. On the HF diet, A/J
males remained lean and were resistant to NASH, whereas B6 males were obese and
showed histological and biochemical features of NASH, and in many cases NASH
progressed to HCCs with molecular and histological features that were remarkably
similar to those reported for the two major HCC classes in humans. On the LF diet,
both A/J and B6 were resistant to NASH and HCC. Messenger RNA profiles of HCCs
versus tumor-free livers implicated two signaling networks, one centered on Myc and
the other on NF{kappa}B. Also, we tested whether long-term exposure to the HF diet
would give the same response in Chromosome Substitution Strains (CSSs) as with the
parental strains. The B6-ChrA/J CSS panel consists of 22 mouse strains in which
each CSS consist of a single substituted chromosome from a donor strain (A/J) onto
the background of a host strain (B6). We found that most CSSs were resistant to
diet-induced obesity, matching their A/J parent, with a few resembling the obesity
of the B6 parental strain. We selected two strains from the CSS panel, B6-Chr18A/J
which shows diet-induced obesity, and B6-Chr5A/J, an obesity resistant strain, to
test long-term HF diet effects. Although initially lean during short-term HF diet
tests, B6-Chr5A/J eventually became obese and showed a strong susceptibility to
NASH and HCC. By contrast, B6-Chr18A/J remained obese throughout the long-term
study, but remarkably maintained features of a normal liver, showed a greatly
reduced susceptibility to NASH, and complete resistance to HCC. These studies show
that complex interactions between genetic and dietary factors modulate
susceptibility to liver disease and cancer.
+1&spage=2413&pages=&date=2011&title=Cancer+Research&atitle=Diet-induced+non-
alcoholic+steatohepatitis+and+hepatocellular+carcinoma+in+chromosome+substitution+s
trains+of+mice&aulast=Hill-Baskin&pid=%3Cauthor%3EHill-Baskin+A.E.%3BSpiezio+S.H.
%3BDeSantis+D.%3BCroniger+C.%3BLambris+J.D.%3BNadeau+J.H.%3BBerger+N.A.%3C%2Fauthor
%3E%3CAN%3E70687684%3C%2FAN%3E%3CDT%3EConference+Abstract%3C%2FDT%3E
<104>
Accession Number
70591879
Title
IL-6/STAT3-induced mtor and autophagy signaling in obesity-promoted liver cancer.
Source
Author
Park E.J.; Dhar D.; Lee J.H.; Kim H.S.; Li N.; Ali S.R.; Budanov A.V.; Paik Y.H.;
Iwaisako K.; Karin M.; Brenner D.; Seki E.
Institution
(Park, Kim, Ali, Iwaisako, Brenner, Seki) Medicine, University of California, San
Diego, San Diego, CA, United States
(Dhar, Lee, Li, Budanov, Karin) Pharmacology, University of California, San
Diego, San Diego, CA, United States
(Paik) Internal Medicine, Yonsei University, College of Medicine, Seoul, South
Korea
Publisher
Subject Headings
*autophagy
*liver cancer
*obesity
*liver
*liver disease
mouse
fatty liver
tumor
mouse mutant
lipid storage
protein expression
protein synthesis
lipid metabolism
inflammation
odontoid process
feeding
lipid diet
immunoblotting
staining
upregulation
macrophage
tumor cell
cell proliferation
secretion
*interleukin 6
*STAT3 protein
rapamycin
messenger RNA
diethylnitrosamine
mammalian target of rapamycin
marker
protein p62
peroxisome proliferator activated receptor
Drug Index Terms
*interleukin 6; *STAT3 protein; rapamycin; messenger RNA; diethylnitrosamine;
mammalian target of rapamycin; marker; protein p62; peroxisome proliferator
activated receptor
Other Index Terms
*autophagy; *liver cancer; *obesity; *liver; *liver disease; mouse; fatty liver;
tumor; mouse mutant; lipid storage; protein expression; liver cell carcinoma;
protein synthesis; lipid metabolism; inflammation; odontoid process; feeding; lipid
diet; immunoblotting; staining; immunohistochemistry; upregulation; macrophage;
tumor cell; cell proliferation; secretion
Abstract
BACKGROUND: Obesity promotes hepatocellular carcinoma (HCC) development by
enhancing liver steatosis and steatohepatitis through IL-6 and TNF signals.
Mammalian target of rapamycin (mTOR) which induces protein synthesis, proliferation
and lipid metabolism, but negatively regulates autophagy, is activated in fatty
livers and obesity-promoted HCC (Ob-HCC) despite blunted AKT upstream signaling.
Thus, the signaling upstream of mTOR, and the role of mTOR and autophagy in Ob-HCC
development are unknown. AIM: To determine (1) if inhibition of mTOR signaling
prevents Ob-HCC growth, (2) if IL- 6/STAT3 mediates mTOR signaling and autophagy
inhibition in Ob-HCC, and (3) if inhibition of mTOR signaling reduces fat
accumulation and inflammation in fatty livers. METHOD(S): Twoweek- old WT or IL-6
KO mice were injected with diethylnitrosamine (DEN, 25 mg/kg, ip) followed by
feeding of low- (LFD) or high-fat diet (HFD) for an additional 8 months.
Alternatively, WT HCC-bearing obese mice were treated with vehicle or rapamycin (5
mg/kg/day, ip) for two weeks prior to 8 months. mRNA and protein expressions in
livers and tumors were assessed by qRT-PCR and immunoblotting, respectively. Oil
Red O staining and immunohistochemistry were performed. RESULT(S): HCC size was
significantly reduced in rapamycintreated mice in which mTOR signaling is inhibited
compared to vehicle-treated mice (9.9 mm +/- 6.6 vs 3.9 mm +/- 2.2). While Ob-HCC
exhibited a 6-fold increase in the ratio of mRNA levels of Raptor/Rictor, mTOR
regulatory subunits, compared to HCC in lean mice, rapamycin-treated WT Ob-HCC and
HCC in IL-6 KO mice kept the ratio unchanged. In addition, the loss of IL-6
dramatically inhibited the accumulation of the autophagy marker p62 protein in both
Ob-HCC and non-tumor livers, suggesting upregulation of autophagy in the livers of
IL-6 KO mice compared to WT mice. STAT3 KO mice abolished the defect of autophagy
induced by IL-6. Rapamycin treatment suppressed fat accumulation and macrophage
infiltration (by 37% and 56%, respectively). PPARgamma protein expression and tumor
cell proliferation were also reduced in Ob-HCC (by 52% and 62%, respectively) after
rapamycin treatment. CONCLUSION(S): This study demonstrates that IL-6 regulates
mTOR and autophagy signaling through STAT3 during Ob-HCC development. These results
suggest that mTOR has important roles in the development of hepatic steatosis and
steatohepatitis in obese mice. Furthermore, IL-6 secretion in obesity leads to the
increase in Raptor/Rictor ratio and induces the autophagy defect, thereby resulting
in fatty livers and Ob-HCC.
+1&spage=388A&pages=388A&date=2011&title=Hepatology&atitle=IL-6%2FSTAT3-
induced+mtor+and+autophagy+signaling+in+obesity-
promoted+liver+cancer&aulast=Park&pid=%3Cauthor%3EPark+E.J.%3BDhar+D.%3BLee+J.H.
%3BKim+H.S.%3BLi+N.%3BAli+S.R.%3BBudanov+A.V.%3BPaik+Y.H.%3BIwaisako+K.%3BKarin+M.
%3BBrenner+D.%3BSeki+E.%3C%2Fauthor%3E%3CAN%3E70591879%3C%2FAN%3E%3CDT
<105>
Accession Number
363046659
PMID
Title
Polycystic ovarian syndrome incidence in young women with non-alcoholic epatic
steatosis.
Source
Minerva Ginecologica. 63(5) (pp 429-437), 2011. Date of Publication: October
2011.
Author
Ciotta L.; Pagano I.; Stracquadanio M.; Formuso C.
Institution
(Ciotta, Pagano, Stracquadanio, Formuso) Istituto di Patologia Ostetrica e
Ginecologica, Universita degli Studi di Catania, Catania, Italy
Publisher
Edizioni Minerva Medica S.p.A. (Corso Bramante 83-85, Torino 10126, Italy)
Subject Headings
article
body mass
disease severity
echography
female
glucose blood level
human
incidence
insulin blood level
liver cirrhosis
liver function
obesity
*ovary polycystic disease
portal vein blood flow
Drug Index Terms
glucose / endogenous compound; insulin / endogenous compound
Other Index Terms
article; body mass; disease severity; echography; female; glucose blood level;
human; incidence; insulin blood level; liver cell carcinoma; liver cirrhosis; liver
function; *nonalcoholic fatty liver; obesity; *ovary polycystic disease; portal
vein blood flow
Abstract
Aim. Recently, numerous studies have shown significant correlation between
hyperandrogenism and elevated insulin levels in many patients with polycystic
ovarian syndrome (PCOS). Insuline-Resistance (IR) results in increased circulating
levels of this hormone and it is the basis of the metabolic syndrome, characterized
by the presence of fatty liver disease (NAFLD), which is pathologically
characterized by the accumulation of triglycerides as macro or micro vesicles, in
more than 5% of hepatocytes. The aim of our study was to evaluate the incidence of
NAFLD in young women with PCOS, who were lean, overweight or obese. Methods.
Particularly, the levels of glucose and insulin, the lipidic profile, and all liver
function indices were evaluated; the severity and degree of steatosis were
established on the basis of parenchymal echogenicity and the view of intrahepatic
venous circulation. Results. Our study showed that NAFLD is a common disease in
women with polycystic ovaries, especially with high BMI, but an incidence rate of
40% in lean women too was found. Because steatohepatitis is a risk factor for the
developmente of cirrhosis and hepatocellular carcinoma, it is therefore prudent to
carry out an ultrasound evaluation of liver in all young patients suffering from
polycystic ovary syndrome, regardless of their BMI and the results of serological
evaluation of liver. Conclusion. This collateral diagnosis that accompanies the
diagnosis of Polycystic Ovary Syndrome seems important since this type of patients
could be treated with metformin or with thiazoles to reduce insulin-resistance and
steatosis as well.
sid=OVID:embase&id=pmid:21926952&id=doi:&issn=0026-
437&date=2011&title=Minerva+Ginecologica&atitle=Incidenza+di+sindrome+dell
%27ovaio+policistico+in+giovani+donne+affette+da+steatosi+epatica+non+alcolica&aula
st=Ciotta&pid=%3Cauthor%3ECiotta+L.%3BPagano+I.%3BStracquadanio+M.%3BFormuso+C.%3C
%2Fauthor%3E%3CAN%3E363046659%3C%2FAN%3E%3CDT%3EArticle%3C%2FDT%3E
<106>
Accession Number
70136991
Title
Does non-alcoholic fatty liver disease predispose patients to type 2 diabetes
mellitus?.
Source
Hepatology International. Conference: 20th Conference of the Asian Pacific
Association for the Study of the Liver, APASL. Beijing China. Conference
Publication: (var.pagings). 4(1) (pp 3-4), 2010. Date of Publication: March 2010.
Author
Fan J.-G.
Institution
(Fan) Department of Gastroenterology, Xinhua Hospital Shanghai, Jiaotong
University School of Medicine, Shanghai 200092, China
Publisher
Springer New York
Subject Headings
*Asian
*patient
*liver
*liver disease
*non insulin dependent diabetes mellitus
diabetes mellitus
obesity
risk
risk factor
ultrasound
insulin resistance
mortality
fatty liver
liver cirrhosis
metabolic disorder
impaired glucose tolerance
abdominal obesity
attributable risk
morbidity
family history
cardiovascular risk
kidney disease
intraabdominal fat
inflammation
oxidative stress
etiology
serum
diet restriction
glucose blood level
early intervention
population
death
liver enzyme
adiponectin
glucose
insulin sensitizing agent
Drug Index Terms
liver enzyme; adiponectin; glucose; insulin sensitizing agent
Other Index Terms
*Asian; *patient; *liver; *liver disease; *non insulin dependent diabetes
mellitus; *nonalcoholic fatty liver; diabetes mellitus; obesity; risk; risk factor;
ultrasound; insulin resistance; mortality; fatty liver; liver cirrhosis; metabolic
syndrome X; metabolic disorder; impaired glucose tolerance; abdominal obesity;
attributable risk; morbidity; cardiovascular disease; family history;
cardiovascular risk; liver cell carcinoma; kidney disease; intraabdominal fat;
inflammation; oxidative stress; etiology; serum; diet restriction; glucose blood
level; early intervention; lifestyle modification; population; death
Abstract
Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are
associated with each other more frequently than expected by chance. NAFLD is
present in approximately 80% of T2DM, and the latter occurs in 21-45% of patients
with NAFLD. T2DM per se may generate liver disease of metabolic origin (the so-
called NAFLD), and the latter is now considered as the hepatic manifestation of
metabolic syndrome (MetS). However, it is a matter for debate whether DM in the
absence of other metabolic disorders could be a risk factor for the development and
progression of NAFLD. On the other hand, NAFLD may be regarded as having
"prediabetes" indicating the relatively high risk for future diabetes as well as
cardiovascular disease (CVD). In several studies, ultrasound-diagnosed NAFLD and/or
unexplainedelevation of liver enzymes predicted diabetes risk, independent of
obesity and other components of MetS. Compared with overall obesity and abdominal
obesity, ultrasound-diagnosed fatty liver had the highest positive predictive value
and most attributable risk as a percentage for detecting risk factors clustering.
Thus, the concept has arisen that NAFLD may signify more than just the presence of
a liver disease; it may also be an early mediator of T2DM and MetS. Both T2DM and
hepatogenous diabetes are associated with increased liver-related morbidity and
mortality in cirrhotic patients regardless of etiology. Unlike the hepatogenous
diabetes attributed to cirrhosis, T2DM in NAFLD is more frequently associated with
risk factors such as age, BMI, and family history of T2DM. The finding of diabetes
is associated with an increased risk of all-cause death and liver-related mortality
in patients with NAFLD, and diabetic and cardiovascular risk may compete with
liver-related complications in dictating the final outcome. Both NAFLD in T2DM and
T2DM in NAFLD are associated with a greater risk of progression to NASH, cirrhosis,
hepatocellular carcinoma, CVD and even renal disease. The biological mechanisms by
which NAFLD contributes to a higher risk of developing T2D are not fully
understood. However, the fatty liver could contribute in the same way as visceral
adipose tissue to insulin resistance, systemic inflammation and oxidative stress,
while the decreased serum adiponectin concentrations might also be part of the
mechanism. Interestingly, among subjects with NAFLD, only insulin resistance was
predictive of diabetes development, whereas among subjects without NAFLD, obesity
in addition to insulin resistance was associated with subsequent diabetes. In
summary, subjects with ultrasound-diagnosed NAFLD and/or unexplained liver enzymes
elevation are associated with a high incidence of type 2 DM and metabolic
complications in the near future. They would benefit from being screened regularly
for the development of diabetes by fasting plasma glucose and oral glucose tolerant
test. This could be of particular importance in apparently lean individuals whose
only evidence of central adiposity is NAFLD. Furthermore, identification of NAFLD
provides a point of early intervention in the form of advice about lifestyle
modification and insulin-sensitizers. Interventions to prevent the development of
diabetes among the vast population of overweight and obese individuals may be more
efficacious if targeted particularly at those with concomitant NAFLD.
4&date=2010&title=Hepatology+International&atitle=Does+non-
alcoholic+fatty+liver+disease+predispose+patients+to+type+2+diabetes+mellitus
%3F&aulast=Fan&pid=%3Cauthor%3EFan+J.-G.%3C%2Fauthor%3E%3CAN%3E70136991%3C%2FAN%3E
<107>
Accession Number
39490674
Title
Non alcoholic fatty liver: An emerging disease of metabolic origin.
Source
Giornale Italiano di Diabetologia e Metabolismo. 24(3) (pp 107-115), 2004. Date
of Publication: September 2004.
Author
Marzocchi R.; Zannoni C.; Moscatiello S.; Marchesini G.
Institution
(Marzocchi, Zannoni, Moscatiello, Marchesini) Malattie del Metabolismo, Alma
Mater Studiorum Univ. Bologna, Bologna, Italy
(Marchesini) Cattedra di Malattie del Metabolisme, Alma Mater Studiorum Univ.
Bologna, Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy
Publisher
UTET Periodici Scientifici srl (via Montefeltro 6/A, Milano 20156, Italy)
Subject Headings
age
alcohol abuse
disease course
dyslipidemia
fatty liver
gene expression
health behavior
hepatitis
heredity
histology
human
insulin resistance
lifestyle
lipid peroxidation
lipid storage
liver cell
liver cell carcinoma/co [Complication]
liver cirrhosis/co [Complication]
liver disease/ep [Epidemiology]
liver fibrosis
liver necrosis
*metabolic disorder/dt [Drug Therapy]
non insulin dependent diabetes mellitus/dt [Drug Therapy]
obesity
pathogenesis
patient selection
phlebotomy
prevalence
race difference
review
weight reduction
antioxidant/dt [Drug Therapy]
atorvastatin/dt [Drug Therapy]
betaine/dt [Drug Therapy]
bezafibrate/dt [Drug Therapy]
insulin sensitizing agent/dt [Drug Therapy]
metformin/dt [Drug Therapy]
rosiglitazone/dt [Drug Therapy]
tetrahydrolipstatin/dt [Drug Therapy]
Drug Index Terms
alpha tocopherol / drug therapy; antioxidant / drug therapy; atorvastatin / drug
therapy; betaine / drug therapy; bezafibrate / drug therapy; insulin / endogenous
compound; insulin sensitizing agent / drug therapy; metformin / drug therapy;
pioglitazone / drug therapy; rosiglitazone / drug therapy; tetrahydrolipstatin /
drug therapy
Other Index Terms
age; alcohol abuse; disease course; dyslipidemia; fatty liver; gene expression;
health behavior; hepatitis; heredity; histology; human; insulin resistance;
lifestyle; lipid peroxidation; lipid storage; liver cell; liver cell carcinoma /
complication; liver cirrhosis / complication; liver disease / epidemiology; liver
fibrosis; liver necrosis; *metabolic disorder / *drug therapy; non insulin
dependent diabetes mellitus / drug therapy; *nonalcoholic fatty liver /
*diagnosis / *drug therapy / *epidemiology; obesity; pathogenesis; patient
selection; phlebotomy; prevalence; race difference; review; weight reduction
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an emerging clinical entity, ranging
from pure fatty liver to fibrosis, necroinflammation, and eventually cirrhosis and
hepatocellular carcinoma. Hystologically, NAFDL resembles liver lesions found in
alcohol abuse, but it develops in subjects who drink no more than 20 g of alcohol
per day. The prevalence of NAFLD ranges between 10 and 25% of the general
population, with differences according to age and race. Insulin resistance is the
common soil in the pathogenesis of NAFDL. It causes lipid overload to hepatocytes
and lipid peroxidation facilitates disease progression. NAFLD was proposed as part
of the metabolic syndrome; accordingly, type 2 diabetes, obesity and dyslipidemia
are the most prevalent associated findings. However, NAFLD can also be diagnosed in
normal weight, non-diabetic subjects, suggesting a genetic basis of the disease in
selected patients. In the majority of patients inappropriate lifestyle behaviours
could facilitate gene expression. Great attention was recently given to NAFLD, due
to the increasing prevalence of obesity and diabetes in the general population,
which puts a large number of patients at risk of advanced liver disease in the next
decades. Therapeutic strategies aimed at reducing insulin resistance by weight loss
and the use of insulin-sensitizing agents, associated to antioxidant agents, are
currently under study with promising results.
115&date=2004&title=Giornale+Italiano+di+Diabetologia+e+Metabolismo&atitle=La+steat
osi+epatica+non+alcolica
%3A+Una+patologia+emergente+di+interesse+metabolico&aulast=Marzocchi&pid=%3Cauthor
%3EMarzocchi+R.%3BZannoni+C.%3BMoscatiello+S.%3BMarchesini+G.%3C%2Fauthor%3E%3CAN

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