ALD, NAFLD, Cirrhosis

LIVER AND BILIARY
TRACT
GASTROENTEROLOGY MODULE
Stephanie Mae Cabilao-Maala, MD, FPCP

Course Outline
• Approach to the Patient with Liver Disease
• Evaluation of Liver Function
• The Hyperbilirubinemias
• Acute Viral Hepatitis
• Toxic and Drug-Induced Hepatitis
• Chronic Hepatitis
• Alcoholic Liver Disease
• Non-alcoholic Liver Disease
• Cirrhosis and it’s complications
• Diseases of the Gallbladder and Bile Ducts
Reference
• Harrison’s Principle’s of Internal Medicine 20th Edition

Alcoholic Liver
Disease
Course Objectives
• Describe the different lesions associated with alcoholic
liver disease
• Identify risk factors for Alcoholic liver disease
• Describe clinical and laboratory features of alcoholic liver

disease and its management and prognosis
Alcoholic Liver Disease
• Three major lesions:
• Fatty Liver- initial and most common histologic

response to hepatotoxic stimuli
• Alcoholic Hepatitis
• Cirrhosis
Alcoholic Liver Disease
• Quantity and duration of

alcohol intake
• Most important risk

factor involved in the
development of
alcoholic liver disease
HPIM 20th Ed. Ch. 335

Alcoholic Hepatitis
• Hallmark: ballooning degeneration, spotty necrosis, PMN
infiltrate, fibrosis in the perivenular and perisinusoidal
space of Disse
• Mallory-Denk bodies- non-specific
• Reversible but presence is associated with progressive

liver injury
Clinical Features
• Hepatomegaly
• Alcoholic hepatitis—fever, spider nevi, jaundice,

abdominal pain
• Cirrhosis- same as other causes

Laboratory Features

Prognosis
• Severe alcoholic hepatitis
• Coagulopathy, anemia, hypoalbuminemia.

Hyperbilirubinemia, renal failure, ascites
• Maddrey Discriminant Function >32 – poor prognosis
• MELD
Treatment
• Complete abstinence- Cornerstone of treatment
• Glucocorticoids- alcoholic hepatitis
• DF >32; MELD >20
• Prednisone 40mg/day or Prednisolone 32mg/day for 4

weeks then taper
Treatment
Lille score
- Day 7 of glucocorticoids
- Determine
pretreatment variables
+ change in bilirubin
- Score > 0.45 à

indicates nonresponse
to therapy

• Questions?
Nonalcoholic Fatty
Liver Disease
Course Objectives
• Describe the spectrum of pathology in NAFLD
• Identify clinical and laboratory features of NAFLD
• Describe the treatment plan for NAFLD

Nonalcoholic Fatty Liver
Disease (NAFLD)
• Associated with obesity/overweight and insulin resistance

Disease (NAFLD)
Wang, Jin & He, Wanping & Tsai, Ping-Ju & Chen, Pei-Hsuan & Ye, Manxiang & Guo, Jiao & Su, Zhengquan. (2020). Mutual interaction between
endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease. Lipids in Health and Disease. 19. 10.1186/s12944-020-01210-0.
Disease (NAFLD)
• Diagnosis
• Increased liver fat in the absence of hazardous levels of

alcohol consumption
• No one specific test for NAFLD
• Important to identify NAFLD risk factors

High BMI
T2DM/Insulin resistance
Metabolic syndrome
Disease (NAFLD)
• Establish severity of NAFLD-related liver injury
• Distinguish patients with NASH from those with simple

steatosis
• Blood test for evidence of hepatic dysfunction
• PE: identify stigmata of portal hypertension
• Gold standard: Liver biopsy

Disease (NAFLD)
• Clinical Features
• Asymptomatic
• Vague RUQ pain, hepatomegaly
• Obese patients (50-90%); features of metabolic

syndrome
• Stigmata of Chronic liver disease

Disease (NAFLD)
• Treatment
• Specific therapy of NAFLD-related liver disease
• Treatment of NAFLD-associated comorbidities
• Treatment of complications
Disease (NAFLD)
• Specific therapy of NAFLD-related diseases
• Manage complication of cirrhosis and portal

hypertension
• Treat risk factor for NASH
• NASH/ features of hepatic fibrosis on liver biopsy
• May receive targeted pharmacologic therapy

Disease (NAFLD)
• Diet and Exercise
• Weight loss up to 10% improves steatohepatitis
• Pharmacologic
• Vitamin E (800IU/d)- first line therapy for nondiabetic

NASH patients
Disease (NAFLD)
• Bariatric Surgery
• BMI >40
• Liver transplantation
• In NAFLD patients with end stage liver disease

• Questions?
Liver Cirrhosis
Course Objectives
• Describe the clinical features of liver cirrhosis
• Discuss the different causes of cirrhosis
• Discuss treatment management of liver cirrhosis
• Discuss the common complications of portal

hypertension: esophageal varices and Ascites
Liver Cirrhosis
• Development of fibrosis in the
liver causing architectural
distortion with formation of
regenerative nodules
• Decrease in hepatocellular
mass and function
https://www.healthxchange.sg/digestive-
• Alteration of blood flow

system/liver/liver-cirrhosis-causes-risk-factors
Liver Cirrhosis

Liver Cirrhosis
• Clinical Features
• Result of the pathologic changes and mirror the

severity of liver disease
• Loss of hepatocellular function
• Jaundice, coagulopathy, hypoalbuminemia
• Portal hypertension
• Ascites, bleeding esophagogastric varices

Alcoholic Cirrhosis
• Micronodular cirrhosis – nodules <3mm in diameter
• Diagnosis requires accurate history of amount and

duration of alcohol consumption
• Labs:
• Serum bilirubin- normal or elevated
• Protime- prolonged and do not respond to Vit K
• Serum sodium—normal to decreased
• AST/ALT 2:1
Alcoholic Cirrhosis
• Treatment
• Abstinence
• Nutrition support
• Long-term monitoring
• Glucocorticoids- in severe alcoholic hepatitis in the

absence of infection
• DF >32
Cirrhosis due to Chronic
Hepatitis B and C
• 20-30% of Chronic Hepatitis C will develop cirrhosis over
20-30 years
• 20% of chronic hepatitis B will develop cirrhosis
• Clinical features similar as to cirrhosis of other causes

Cirrhosis due to Chronic
Hepatitis B and C
• Treatment:
• Antiviral therapy beneficial

Cirrhosis from other
causes
• Autoimmune Hepatitis
• NAFLD
• Primary Biliary Cholangitis
• Primary Sclerosing Cholangitis
• Cardiac Cirrhosis- long standing right sided CHF
Major Complications of
Cirrhosis

Portal Hypertension
• Elevation of hepatic venous pressure gradient (HVPG) to
>5mmHg
• Due to the following processes:
• Inc intrahepatic resistance to blood flow d/t cirrhosis
• Inc splanchnic blood flow from vasodlation

Portal Hypertension
• 2 major complications:
• Variceal hemorrhage
• Ascites
Sharara,AI et al. Gastroesophageal Variceal Hemorrhage.N Engl J Med 2001; 345:669-681

Portal Hypertension
>95%

Portal Hypertension
• Diagnosis
• Thrombocytopenia
• Splenomegaly
• Development of ascites, encephalopathy, esophageal

varices +/- bleeding
Esophageal varices
• Develop in 5-15% of cirrhotics per
year
• 1/3 of patients with varices will

bleed
• Severity of cirrhosis predict risk for

bleeding e.g. MELD score, Child-
Pugh Class
Esophageal Varices
• Treatment
• Variceal hemorrhage
• Primary prophylaxis-
screening endoscopy
• Beta blockade or variceal

band ligation
• Secondary prophylaxis-
Prevention of rebleeding
Portal Hypertension

Ascites
• Accumulation of fluid within
the peritoneal cavity
• Increase in abdominal girth
• Shortness of breath in
massive ascites
• Diagnosed by PE,
abdominal imaging
Ascites
Ascites
• New onset ascites- diagnostic paracentesis
recommended
• Determination of Ascitic albumin, total protein, blood

cell counts, cultures
• Serum ascites-to—albumin gradient (SAAG)
• >1.1g/dlà most likely due to portal hypertension

Ascites
• Treatment
• Minimal ascites- dietary sodium restriction (<2g Na per day)
• Moderate ascites- diuretic therapy
• Spironolactone 100-200mg/day (max 600mg/day)
• Furosemide 40-80mg/day (max 160mg/day)
• Refractory Ascites
• Large volume ascites
• TIPS
• Questions?

ALD, NAFLD, Cirrhosis

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LIVER AND BILIARY

Stephanie Mae Cabilao-Maala, MD, FPCP

• Harrison’s Principle’s of Internal Medicine 20th Edition

• Identify risk factors for Alcoholic liver disease

• Describe clinical and laboratory features of alcoholic liver

• Fatty Liver- initial and most common histologic

• Quantity and duration of

• Most important risk

HPIM 20th Ed. Ch. 335

• Mallory-Denk bodies- non-specific

• Reversible but presence is associated with progressive

• Alcoholic hepatitis—fever, spider nevi, jaundice,

• Cirrhosis- same as other causes

HPIM 20th Ed. Ch. 335

• Coagulopathy, anemia, hypoalbuminemia.

• Maddrey Discriminant Function >32 – poor prognosis

• Glucocorticoids- alcoholic hepatitis

• DF >32; MELD >20

• Prednisone 40mg/day or Prednisolone 32mg/day for 4

- Score > 0.45 à

HPIM 20th Ed. Ch. 335

• Identify clinical and laboratory features of NAFLD

• Describe the treatment plan for NAFLD

• Associated with obesity/overweight and insulin resistance

• Increased liver fat in the absence of hazardous levels of

• No one specific test for NAFLD

• Important to identify NAFLD risk factors

• Distinguish patients with NASH from those with simple

• Blood test for evidence of hepatic dysfunction

• PE: identify stigmata of portal hypertension

• Gold standard: Liver biopsy

• Vague RUQ pain, hepatomegaly

• Obese patients (50-90%); features of metabolic

• Stigmata of Chronic liver disease

• Specific therapy of NAFLD-related liver disease

• Treatment of NAFLD-associated comorbidities

• Manage complication of cirrhosis and portal

• Treat risk factor for NASH

• NASH/ features of hepatic fibrosis on liver biopsy

• May receive targeted pharmacologic therapy

• Diet and Exercise

• Weight loss up to 10% improves steatohepatitis

• Vitamin E (800IU/d)- first line therapy for nondiabetic

• In NAFLD patients with end stage liver disease

• Discuss the different causes of cirrhosis

• Discuss treatment management of liver cirrhosis

• Discuss the common complications of portal

• Alteration of blood flow

HPIM 20th Ed. Ch. 337

• Result of the pathologic changes and mirror the

• Loss of hepatocellular function

• Jaundice, coagulopathy, hypoalbuminemia

• Ascites, bleeding esophagogastric varices

• Diagnosis requires accurate history of amount and

• Glucocorticoids- in severe alcoholic hepatitis in the

• 20% of chronic hepatitis B will develop cirrhosis

• Clinical features similar as to cirrhosis of other causes

• Antiviral therapy beneficial

HPIM 20th Ed. Ch. 337

• Due to the following processes: