Paper II
Question
Alcoholic liver disease
Answer
Alcoholic liver disease comprises a spectrum of progressive hepatic injury from chronic alcohol consumption:
1. Hepatic steatosis (fatty liver):
- Earliest, fully reversible stage; alcohol metabolism shifts hepatocyte metabolism toward lipogenesis (via generation of excess NADH, impairing fatty acid oxidation) and impairs lipoprotein export.
- Gross: Large, soft, yellow, greasy liver.
- Microscopy: Macrovesicular (and initially microvesicular) fat droplets displacing the hepatocyte nucleus to the periphery.
2. Alcoholic hepatitis:
- Follows bouts of heavy drinking; caused by acetaldehyde-mediated hepatocyte toxicity and oxidative stress (from ethanol metabolism via alcohol dehydrogenase and CYP2E1), triggering inflammation.
- Microscopy: Hepatocyte swelling/ballooning degeneration, Mallory-Denk hyaline (eosinophilic cytoplasmic inclusions of damaged intermediate filaments), neutrophilic infiltration around damaged hepatocytes, and pericellular/perivenular (“chicken-wire”) fibrosis.
- Clinically presents with fever, hepatomegaly, jaundice, elevated AST (typically greater than ALT, ratio >2:1); can be life-threatening.
3. Alcoholic (Laennec) cirrhosis:
- End-stage, irreversible, resulting from repeated hepatocyte injury and progressive activation of hepatic stellate cells (Ito cells), which deposit collagen.
- Micronodular pattern with bridging fibrous septa encircling regenerative nodules; complete loss of normal architecture.
- Complications: portal hypertension (varices, splenomegaly, ascites, caput medusae), hepatic encephalopathy, hepatocellular carcinoma, hepatorenal syndrome, coagulopathy.
The stages represent a continuum — steatosis and early hepatitis are reversible with abstinence, while cirrhosis represents irreversible, permanent liver damage.