Pathology · Hepatobiliary and Pancreatic Pathology

The 2021 AASLD/EASL non-alcoholic fatty liver disease (NAFLD) nomenclature change reclassifies a subset of patients. Under the new MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease) framework, a patient with hepatic steatosis AND 1 of 5 cardiometabolic risk factors qualifies. Which histological feature distinguishes metabolic-associated steatohepatitis (MASH) from simple hepatic steatosis and determines prognosis?

  • A Degree of macrovesicular steatosis alone (>66% hepatocytes) determines prognosis and diagnosis of MASH
  • B Portal tract-predominant inflammation with interface hepatitis (similar to autoimmune hepatitis) is the defining feature of MASH versus simple steatosis
  • C Centrilobular vein sclerosis with glycogenated nuclei is pathognomonic for MASH regardless of steatosis grade
  • D Combination of steatosis with hepatocellular ballooning, lobular inflammation, and variable fibrosis — the MASH activity score (NAS ≥5 with ballooning present) — determines diagnosis, with fibrosis stage being the strongest independent predictor of liver-related mortality
Correct answer: D. Combination of steatosis with hepatocellular ballooning, lobular inflammation, and variable fibrosis — the MASH activity score (NAS ≥5 with ballooning present) — determines diagnosis, with fibrosis stage being the strongest independent predictor of liver-related mortality

Explanation

MASH (metabolic-associated steatohepatitis, formerly NASH) is defined histologically by the triad: (1) steatosis (macro- or microvesicular), (2) hepatocellular ballooning (swollen hepatocytes with pale cytoplasm representing cytoskeletal intermediate filament collapse — Mallory-Denk bodies may be present), and (3) lobular inflammation. The NAFLD Activity Score (NAS) grades steatosis (0-3), lobular inflammation (0-3), and ballooning (0-2); NAS ≥5 correlates with MASH. However, fibrosis stage (F0-F4) is the single most powerful predictor of liver-related and overall mortality — more so than NAS itself. Simple steatosis (without ballooning or significant inflammation) has a benign prognosis. Portal-predominant inflammation is more typical of viral hepatitis or autoimmune hepatitis.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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