alcoholic liver disease
Summary
Alcoholic liver disease (ALD) represents a spectrum of liver damage from chronic alcohol use, progressing from reversible hepatic steatosis (fatty liver) to alcoholic hepatitis to irreversible cirrhosis. It is a major cause of liver-related morbidity/mortality and is diagnosed based on history, AST:ALT ratio >2:1, and clinical/imaging findings.
Detail
Pathophysiology: Chronic ethanol metabolism generates excess NADH via alcohol dehydrogenase and acetaldehyde dehydrogenase, shifting hepatocyte metabolism toward lipogenesis and away from fatty acid oxidation, causing macrovesicular steatosis. Acetaldehyde (toxic metabolite) causes hepatocyte injury, mitochondrial dysfunction, and protein adduct formation, triggering inflammation. CYP2E1 induction produces reactive oxygen species, contributing to oxidative stress and lipid peroxidation. Chronic injury activates hepatic stellate cells, leading to fibrosis and eventual cirrhosis.
Spectrum of disease: 1. Hepatic steatosis (fatty liver) - reversible with cessation, often asymptomatic, hepatomegaly. 2. Alcoholic hepatitis - inflammation with hepatocyte necrosis, Mallory-Denk bodies (eosinophilic intracytoplasmic inclusions), neutrophilic infiltration, fever, jaundice, tender hepatomegaly, elevated AST/ALT (AST:ALT >2:1, both usually <500), leukocytosis. Severe cases assessed with Maddrey's discriminant function; may be treated with corticosteroids. 3. Cirrhosis - irreversible fibrosis with regenerative nodules, risk of portal hypertension, ascites, variceal bleeding, hepatic encephalopathy, hepatocellular carcinoma.
Clinical/Lab findings: Elevated GGT, macrocytic anemia (MCV elevated from direct marrow toxicity/folate deficiency), thrombocytopenia, hypoalbuminemia, elevated INR in advanced disease. Physical exam may show spider angiomata, palmar erythema, gynecomastia, testicular atrophy, caput medusae, asterixis.
Management: Alcohol cessation is cornerstone of therapy. Nutritional support, corticosteroids for severe alcoholic hepatitis, consideration of liver transplant in select cases (typically requiring sobriety period). Screen for and manage complications of cirrhosis and portal hypertension.
High-yield associations: AST:ALT ratio >2:1 is classic for alcoholic liver disease (due to pyridoxal-5-phosphate deficiency affecting ALT synthesis more than AST). Mallory bodies are composed of damaged cytokeratin filaments. Zone 3 (centrilobular) is most susceptible to alcohol-induced injury due to highest CYP2E1 concentration and relative hypoxia.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- Harrison's Principles of Internal Medicine
- UpToDate: Alcoholic liver disease
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