Papers by Richard Sterling
Gastroenterology & hepatology, 2006
Human immunodeficiency virus and hepatitis C virus are global health concerns. Due to shared rout... more Human immunodeficiency virus and hepatitis C virus are global health concerns. Due to shared routes of transmission, coinfection is common. Since the introduction of highly active antiretroviral therapy in the mid-1990s and the associated marked reduction in HIV-related mortality, the incidence of liver-related mortality in coinfected patients has risen significantly. This rise has led to increased research into the evaluation and management of the coinfected patient. This article reviews the epidemiology and evaluation of the coinfected patient and outlines the principles necessary for successful management of this challenging patient population.
Evidence Based Medicine, 2014
Context Hepatitis C virus (HCV) infects over 185 million people worldwide and can lead to progres... more Context Hepatitis C virus (HCV) infects over 185 million people worldwide and can lead to progressive liver fibrosis, cirrhosis, hepatocellular carcinoma and death. Antiviral treatment can prevent these complications and improve survival. Interferon has been the backbone of anti-HCV therapy, but has been plagued by side effects, treatment failure and relapse. HCV treatment has seen significant changes with the advent of directly acting antiviral agents with nearly 100% cure rate with all oral, interferon and ribavirin-free regimens.
Journal of Viral Hepatitis, 2011
This study assessed the association of HIV RNA with indirect markers of liver injury including FI... more This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV) co-infected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs. undetectable, <400 copies/ml) was associated with a 40% greater odds (OR 1.4, 95% CI: 1.1-1.9, p=0.016) of FIB-4 > 1.45 in the HIV/HCV co-infected group and 70% greater odds of FIB-4 >1.45 (OR 1.7, 95% CI: 1.0-2.8; p=0.046) in the HIV mono-infected group. In multivariable analyses a 1 log 10 increase in HIV RNA was associated with a median increase in FIB-4 of 12% in the HIV/HCV co-infected group and 11% in the HIV mono-infected group (p<0.0001). Among the HIV/HCV co-infected, the elevating effect of HIV RNA on FIB-4 was strongest at low CD4 counts (p=0.0037). Among the HIV mono-infected, the association between HIV RNA and FIB-4 was independent of CD4 cell counts. HIV RNA was associated with alterations in both liver enzymes and platelet counts. HIV antiretroviral therapy was not associated with any measure of liver injury examined. This study suggests that HIV may have direct, injurious effects on the liver and that HIV viral load should be considered when these indirect markers are used to assess liver function.
Clinical Infectious Diseases, 2005
Hepatitis C virus (HCV) coinfection is common in patients infected with human immunodeficiency vi... more Hepatitis C virus (HCV) coinfection is common in patients infected with human immunodeficiency virus (HIV), because the viruses share common routes of transmission. With the marked increase in life expectancy of HIV-infected patients associated with the use of highly active antiretroviral therapy, HCV infection has become a significant cause of morbidity and mortality in coinfected patients. As a result, there has been increasing attention to adequate assessment of HCV infection during the last several years. Unlike liver enzymes and HCV RNA levels, which can fluctuate widely and do not correlate with the severity of disease, liver biopsy has become the cornerstone in the evaluation of chronic HCV infection. However, there remain important questions and controversies related to adequately determining the histological severity of liver disease and the role of liver biopsy in HIV-HCV-coinfected patients. Because of their common routes of transmission, coinfection with hepatitis C virus (HCV) and HIV is common [1-3]. With the marked increase in life expectancy of HIV-infected patients associated with the use of highly active antiretroviral therapy (HAART) [4], HCV has become a significant cause of morbidity and mortality in coinfected patients [5-9]. In addition, HCV is associated with increased incidence of hepatotoxicity due to HAART [10, 11]. As a result, there has been increasing attention to adequate assessment of HCV infection during the last several years. Unlike liver enzymes and HCV RNA levels, which can fluctuate widely and do not correlate with the severity of disease, liver biopsy has become the cornerstone in the evaluation of chronic HCV infection. However, there remain important questions and controversies related to adequately determining the histological severity of liver disease in HIV-HCV-coinfected patients. This review highlights several of these issues, including the role of liver biopsy and the use of noninvasive tests to predict
Cancer, 1996
The aim of this study was to elucidate the usefulness of measuring the positive status of both de... more The aim of this study was to elucidate the usefulness of measuring the positive status of both des‐γ‐carboxy prothrombin (DCP) and α‐fetoprotein (AFP) preoperatively as a new prognostic indicator of hepatocellular carcinoma (HCC).
JAMA network open, Apr 10, 2023
IMPORTANCE Disparities in treatment initiation may affect outcomes, but data on racially diverse ... more IMPORTANCE Disparities in treatment initiation may affect outcomes, but data on racially diverse populations with chronic hepatitis B virus (HBV) infection are limited. OBJECTIVE To examine whether HBV treatment initiation and outcomes differ among racial groups.
Clinical Infectious Diseases, Sep 1, 2020
See the Editorial commentary by Woreta and chalasani on pages e3286-7.) Background. Hepatitis B v... more See the Editorial commentary by Woreta and chalasani on pages e3286-7.) Background. Hepatitis B virus (HBV) and fatty liver disease (FLD) are common in human immunodeficiency virus (HIV). Correlates of FLD and its relationship with alanine aminotransferase (ALT) were examined longitudinally in HIV-HBV coinfection. Methods. From 28/4/2014-7/11/2018, 114 HIV-HBV adults had liver biopsy and were followed for a median of 3 years (ancillary study of Hepatitis B Research Network). Steatohepatitis was based on presence of steatosis, ballooning, and perisinusoidal fibrosis. FLD was defined as ≥5% steatosis and/or steatohepatitis. Results. Median age was 49 years, 93% were male, 51% black, 93% had HIV RNA <400 copies/mL and 83% HBV DNA <1000 IU/mL. Thirty percent had FLD (20% steatosis, 10% steatohepatitis). Those with FLD had higher median triglyceride (171 vs 100 mg/ dL, P < .01) and small, dense LDL (44 vs 29 mg/dL, P < .01) and lower HDL-2-C (9 vs 12 mg/dL, P = .001). After adjusting for age, sex, and alcohol use, white and other versus black race (ORs, 8.49 and 16.54, respectively), ALT (OR, 3.13/doubling), hypertension (OR, 10.93), hyperlipidemia (OR, 4.36), and diabetes family history (OR, 5.38) were associated with having FLD (all P < .05). Steatohepatitis or steatosis alone (vs none) was associated with higher ALT over time (1.93 and 1.34 times higher, respectively; P < .001), with adjustment for age, sex, and HBV DNA. Conclusions. About 30% with HIV-HBV coinfection had FLD including 10% with steatohepatitis. FLD was associated with non-black race, metabolic risks, an atherogenic lipid profile, and elevated ALT over time. Thus, identification of FLD and management of adverse metabolic profiles are critically important in HIV-HBV coinfection. clinical Trial Registration. NCT 01924455.
Journal of General Internal Medicine, Oct 28, 2019
BACKGROUND: The prevalence and risk factors for nonadherence to direct-acting antivirals (DAAs) f... more BACKGROUND: The prevalence and risk factors for nonadherence to direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) in clinical practice settings are under-studied. OBJECTIVES: (1) To quantify DAA non-adherence in the total cohort and among subgroups with and without mental health conditions, alcohol use, and substance use, and (2) to investigate patient-and treatment-level risk factor non-adherence. DESIGN: Prospective, observational cohort study. PARTICIPANTS: A total of 1562 patients receiving DAAs between January 2016 and October 2017 at 11 US medical centers including academic and community practices. MAIN MEASURES: Self-reported medication nonadherence, defined as any missed doses in the past 7 days, surveyed early (T2: at 4 ± 2 weeks) and late in treatment (T3: 2-3 weeks prior to end of treatment). Non-adherence to post-treatment follow-up visits was defined as absence of lab results after DAA therapy completion. KEY RESULTS: Of 1447 patients, 162 (11%) reported non-adherence at T2 or T3. Medical records indicated 262 (17%) of the 1562 participants had not returned for post-treatment visits. At baseline, 37% of patients reported mental health conditions, 15% reported alcohol use, and 23% reported using substances in the previous year. Baseline characteristics associated with DAA nonadherence included alcohol use (OR 1.96), younger age (< 35 years vs. > 55 years: OR 3.40), non-white race (OR > 2.26), and DAA treatment cohort, but not substance use or mental health condition. Non-adherence to follow-up exhibited association with younger age and a higher baseline overall symptom burden. Among 1287 patients with evaluable sustained virologic response (SVR) data, 53 patients (4%) did not achieve SVR. The bivariate correlation between adherence and SVR was negligible (r = 0.01). CONCLUSIONS: DAA non-adherence was low and SVR rates were high. Mental health conditions, substance use, and alcohol use should not disqualify patients from DAA therapy. Patients with alcohol use disorder before DAA therapy initiation may benefit from targeted on-treatment support.
American Journal of Gastroenterology, 2012
Th e search yielded 1095 ACS cases with HBA. Information about gender was available in 384 (35%) ... more Th e search yielded 1095 ACS cases with HBA. Information about gender was available in 384 (35%) cases. Th ere were 142 (37%) men and 242 (63%) women. Th e mean age was 47 (range 16-91) years. Elevated Transaminases were found in 25% (range 5-55%) cases of ACS. In many of these cases, the enzymes became normal on gluten-free diet (GFD). Th e terms used for this condition are Celiac Hepatitis, Reactive Hepatitis or Transaminitis. If basic lab data exclude serious liver disease then these patients may not need extensive liver work-up. Liver biopsy done in a few cases has shown mild infi ltration with infl ammatory cells with no necrosis. Primary Biliary Cirrhosis (PBC) has been seen in 3% cases of ACS. Th is may be due to increased intestinal permeability in CS wherein gut derived antigens may damage the biliary system. Primary Sclerosing Cholangitis (PSC) is seen in 2% of cases of ACS. Both CS & PSC are immune-mediated diseases. Auto-Immune Hepatitis (AIH) is seen in 2% cases of ACS; this may be due to common HLA molecules between AIH & CS. Th e GFD, unlike as in cases of Celiac Hepatitis in general does not improve liver tests in PBS, PSC, and AIH. Th e other HBA noted in CS are (a) Transient gallbladder inertia due to low cholecystokinin production; (b) Fatty liver which may be due to malnutrition; (c) Cryptogenic Cirrhosis; (d) End stage Liver Disease (liver tests may improve in some of these on GFD); (e) Non-alcoholic Fatty Liver; (f) Chronic Hepatitis C; Interferon may activate silent CS; (g) Hemochromatosis; (h) Acute Liver Failure; (i) Hepatocellular Carcinoma. Conclusion: HBA occur in some CS patients.Th e cases of Celiac Hepatitis generally respond to GFD and may not need extensive hepatic work-up. Some other HBA in CS patients may also respond to GFD.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jan 3, 2018
Pilot studies suggest that transplanting hepatitis C virus (HCV)-positive donor (D+) kidneys into... more Pilot studies suggest that transplanting hepatitis C virus (HCV)-positive donor (D+) kidneys into HCV-negative renal transplant (RT) recipients (R-), then treating HCV with direct-acting antivirals (DAA) is clinically feasible. To determine whether this is a cost-effective approach, a decision tree model was developed to analyze costs and effectiveness over a 5-year time frame between 2 choices: RT using a D+/R- strategy compared to continuing dialysis and waiting for a HCV-negative donor (D-/R-). The strategy of accepting a HCV+ organ then treating HCV was slightly more effective and substantially less expensive and resulted in an expected 4.8 years of life (YOL) with a cost of ≈$138 000 compared to an expected 4.7 YOL with a cost of ≈$329 000 for the D-/R- strategy. The D+/R- strategy remained dominant after sensitivity analyses including the difference in RT death probabilities or acute rejection probabilities between using D+ vs D- kidney; time that D-/R- patients waited for RT;...
Liver Transplantation, 2015
Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general p... more Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid‐lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty‐five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow‐up from LT. Additionally, the tradi...
Gastroenterology & hepatology, 2013
Clinical Gastroenterology and Hepatology, 2015
Background & Aims-Nonalcoholic fatty liver disease (NAFLD) is independently associated with incre... more Background & Aims-Nonalcoholic fatty liver disease (NAFLD) is independently associated with increased cardiovascular mortality. Although NAFLD is associated with dyslipidemia, it is not clear whether recently identified markers of cardiovascular risk indicate liver disease progression in patients with histologically confirmed NAFLD. We evaluated an extensive panel of serum markers of cardiovascular risk in non-diabetic patients with histologically proven NAFLD. Methods-We performed a case-control study in which we compared serum levels of laboratory markers of cardiovascular risk among 81 non-diabetic subjects with histologically confirmed NAFLD vs lean (N=81) and obese (N=81) individuals without NAFLD (based on liver fat score, controls). For ex vivo studies, liver tissues were obtained from subjects undergoing elective cholecystectomy or a tissue repository. Results-Subjects with NAFLD had increased serum levels of insulin, triglycerides, and apolipoprotein B (APOB); increased size and concentration of very large density lipoprotein particles; increased concentrations of low-density lipoprotein particles (LDL-Ps) and small-dense
Metabolic Brain Disease, 2014
Objective-Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its fu... more Objective-Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. Aim-To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Hypothesis-Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Methods-Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; Nback (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. Results were compared before/after rifaximin. Results-20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p=0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back
Liver Transplantation, 2012
Journal of Hepatology, 2013
Background-Asymmetric di-methyl arginine (ADMA) is an inhibitor of nitric oxide synthase that acc... more Background-Asymmetric di-methyl arginine (ADMA) is an inhibitor of nitric oxide synthase that accumulates in liver disease and may contribute to hepatic encephalopathy(HE). Aim-To evaluate the association of ADMA with cognition and brain MR spectroscopy(MRS) in cirrhosis. Methods-Cirrhotic patients with/without prior HE and non-cirrhotic controls underwent cognitive testing and ADMA determination. A subgroup underwent brain MRS [Glutamine/ glutamate(Glx), myoinositol(mI), N-acetyl-aspartate(NAA) in parietal white, occipital gray and anterior cingulate(ACC)]. We also tested cognition and ADMA in a cirrhotic subgroup before and 1 month after transjugular intrahepatic portosystemic shunting (TIPS). Cognition and MRS values were correlated with ADMA and compared between groups using multi-variable regression. ADMA levels were compared between those who did/did not develop post-TIPS HE. Results-90 cirrhotics (MELD13, 54 prior HE) and 16 controls were included. Controls had better cognition and lower ADMA, Glx and higher mI compared to cirrhotics. Prior HE patients had worse cognition, higher ADMA and Glx and lower mI compared to non-HE cirrhotics. ADMA was positively correlated with MELD (r=0.58,p<0.0001), abnormal cognitive test number(r=0.66,p<0.0001) and Glx and NAAA (white matter,ACC) and negatively with mI. On regression, ADMA predicted number of abnormal tests and mean Z-score independent of prior HE
Journal of Hepatology, 2013
Background-Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair healthrelated qu... more Background-Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair healthrelated quality-of-life (HRQOL) and cognition in cirrhosis. Aim-To study effect of hyponatremia on cognition, HRQOL and brain MR spectroscopy (MRS) independent of HE. Methods-Four cirrhotic groups(no HE/HN, HE alone, HN alone (sodium<130mEq/L),HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psycho-social and physical sub-scores) and brain MRS (myoinositol(mI) and glutamate +glutamine(Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. Results-82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN and 10 HN, MELD 12, 63% Hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN:3, HN:3.5, HE:6.5,HE+HN:7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP(p<0.0001, all comparisons). Brain MRS showed lowest Glx in HN and highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE,HE+HN and HN) groups compared to no HE/HN
Hepatology, 2009
Specific alterations in hepatic lipid composition characterize the spectrum of nonalcoholic fatty... more Specific alterations in hepatic lipid composition characterize the spectrum of nonalcoholic fatty liver disease (NAFLD), which extends from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). However, the plasma lipidome of NAFLD and whether NASH has a distinct plasma lipidomic signature are unknown. A comprehensive analysis of plasma lipids and eicosanoid metabolites quantified by mass spectrometry was performed in NAFL (n = 25) and NASH (n = 50) subjects and compared with lean normal controls (n = 50). The key findings include significantly increased total plasma monounsaturated fatty acids driven by palmitoleic (16:1 n7) and oleic (18:1 n9) acids content (P < 0.01 for both acids in both NAFL and NASH). The levels of palmitoleic acid, oleic acid, and palmitoleic acid to palmitic acid (16:0) ratio were significantly increased in NAFLD across multiple lipid classes. Linoleic acid (8:2n6) was decreased (P < 0.05), with a concomitant increase in γ-linolenic (18:3n6) and dihomo γ-linolenic (20:3n6) acids in both NAFL and NASH (P < 0.001 for most lipid classes). The docosahexanoic acid (22:6 n3) to docosapentenoic acid (22:5n3) ratio was significantly decreased within phosphatidylcholine (PC), and phosphatidylethanolamine (PE) pools, which was most marked in NASH subjects (P < 0.01 for PC and P < 0.001 for PE). The total plasmalogen levels were significantly decreased in NASH compared with controls (P < 0.05). A stepwise increase in lipoxygenase (LOX) metabolites 5(S)-hydroxyeicosatetraenoic acid (5-HETE), 8-HETE, and 15-HETE characterized progression from normal to NAFL to NASH. The level of 11-HETE, a nonenzymatic oxidation product of arachidonic (20:4) acid, was significantly increased in NASH only. Conclusions: Although increased lipogenesis, desaturases, and LOX activities characterize NAFL and NASH, impaired peroxisomal polyunsaturated fatty acid (PUFA) metabolism and nonenzymatic oxidation is associated with progression to NASH.
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Papers by Richard Sterling