Distribution patterns of cytokeratin antigen determinants in alcoholic and nonalcoholic liver diseases

Aggregation and derangement of cytokeratin intermediate filaments are thought to be the key mechanism in the formation of Mallory bodies in alcoholic liver disease (ALD). To study the incidence and patterns of intracellular distribution of aggregated cytokeratin and to determine its utility as a diagnostic marker of ALD, 108 liver biopsy specimens from patients with various liver abnormalities were examined by an avidin--biotin peroxidase complex technique on paraffin section using a monoclonal antibody to cytokeratins (Hybritech). In normal liver (n = 11), only bile duct epithelium was positive. Both bile ducts and hepatocytes were positive in pathologic livers (n = 97). In ALD, 82 per cent of cases (42 of 51) showed cytokeratin positivity versus 15 per cent (seven of 46) in nonalcoholic liver disease (e.g., chronic hepatitis, nonalcoholic cirrhosis, cholestasis, and primary biliary cirrhosis). The highest incidence (100 per cent, 37 of 37) of positivity was obtained in cases with alcoholic hepatitis and cirrhosis compared with only 36 per cent (five of 14) in alcoholic fatty liver. Mallory bodies were found by the immunoperoxidase method in 71 per cent of cases (30 of 42) versus in 40 per cent (17 cases) by hematoxylin--eosin stain. In alcoholic fatty liver and alcoholic hepatitis, centrilobular hepatocytes showed cytokeratin positivity, whereas such reactivity was seen predominantly at the periphery of the regenerative nodules in alcoholic cirrhosis. A rare periportal hepatocyte was positive in the nonalcoholic group. These findings suggest that the differential distribution patterns of aggregated cytokeratin may be helpful in differentiating alcoholic from nonalcoholic liver diseases.