A 60-year-old obese man with type 2 diabetes presents for evaluation of persistently elevated liver enzymes (ALT 78, AST 62 U/L) for over a year. Alcohol intake is negligible. Hepatitis B surface antigen and anti-HCV are negative. Liver ultrasound shows increased echogenicity. Liver biopsy reveals steatosis (> 5%), lobular inflammation, ballooning hepatocytes, and perisinusoidal fibrosis (stage 2). Which finding on biopsy most strongly predicts progression to cirrhosis?
- A Hepatocyte ballooning degeneration ✓
- B Macrovesicular steatosis degree
- C Lobular inflammation severity
- D Degree of hepatic steatosis (% fat)
Explanation
In metabolic-associated steatohepatitis (MASH, formerly NASH), hepatocyte ballooning degeneration is the histological hallmark that most strongly correlates with fibrosis stage and risk of progression to cirrhosis. Ballooning reflects endoplasmic reticulum stress and is the cellular substrate for activation of hepatic stellate cells and subsequent fibrogenesis. While all components contribute to the NAFLD Activity Score (NAS), fibrosis stage is the strongest predictor of liver-related mortality and is most driven by ballooning. The degree of steatosis alone does not predict fibrosis progression; simple steatosis without ballooning has a benign course.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.