A 40-year-old man with alcoholic liver disease undergoes liver biopsy. Pathology shows eosinophilic hyaline intracytoplasmic inclusions in hepatocytes. These 'Mallory-Denk bodies' are composed primarily of which proteins?

• A Smooth muscle actin and desmin
• B Alpha-1-antitrypsin polymer aggregates
• C Ferritin and haemosiderin deposits
• D Ubiquitin-decorated cytokeratin 8 and 18 intermediate filaments ✓

Explanation

Mallory-Denk bodies are cytoplasmic inclusions formed by abnormal aggregation of cytokeratin 8 and 18 (CK8/18) intermediate filaments that have been ubiquitinated due to disrupted protein quality control in alcoholic liver disease. Alcohol-induced oxidative stress impairs the ubiquitin-proteasome system, causing accumulation of misfolded keratins. They appear as eosinophilic, irregularly shaped perinuclear inclusions. While alcoholic hepatitis is the classic setting, similar inclusions occur in NASH, Wilson disease, and Indian childhood cirrhosis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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