A 38-year-old woman with no alcohol use has NASH-related cirrhosis. Liver biopsy shows Zone 3 perisinusoidal fibrosis, hepatocyte ballooning with Mallory-Denk bodies, lobular inflammation, and steatosis >5%. The NASH Activity Score (NAS) and the degree of fibrosis are used independently. A NAS of ≥5 strongly predicts progressive disease. Mallory-Denk bodies in NASH are composed of:
- A Amyloid precursor protein deposits
- B Alpha-1-antitrypsin polymer inclusions
- C Aggregated keratin 8/18 with p62 and ubiquitin ✓
- D Triglyceride microvesicles in the cytosol
Explanation
Mallory-Denk bodies (MDBs) are cytoplasmic inclusions in ballooned hepatocytes that on ultrastructure represent aggregates of misfolded intermediate filament proteins, primarily keratin 8 and keratin 18, along with p62/sequestosome-1 and ubiquitin. The accumulation results from impaired proteasomal degradation of these keratins, which are vulnerable to oxidative stress in NASH. Immunohistochemically, MDBs stain positively for keratin, p62, and ubiquitin. Alpha-1-antitrypsin globules (PAS-diastase positive round inclusions) are a distinct entity. Triglyceride accumulation causes steatosis but not MDBs.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.