Serum vitamin A deficiency and increased intrahepatic expression of cytokeratin antigen in alcoholic liver disease

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Abstract
The clinical and histologic significance of cytokeratin antigen expression in various intrahepatic locations was assessed in 57 patients with alcoholic liver disease as part of a large Veterans Administration Cooperative Study of Alcoholic Hepatitis. Cytokeratin antigen was demonstrated in fixed, paraffin-embedded liver tissue by an avidin-biotin peroxidase method using a mixture of two different monoclonal antibodies, AE1 (acidic; 48, 50 and 56.5 kD) and AE3 (basic; 52, 56, 58 and 65 to 67 kD). In contrast to the normal liver, in which only bile duct epithelium was positive, this antibody mixture stained both bile ducts and hepatocytes in pathologic livers. Serum levels of vitamin A showed a significant inverse correlation with the amount of cytokeratin antigen (scale: 0 to 3) in hepatocytes without Mallory bodies (p = 0.001), in Mallory body-containing hepatocytes (p < 0.0001) and in bile ducts (p = 0.0074). Increased amount of cytokeratin antigen in each of these locations, in turn, correlated directly with the histologic severity of the liver disease. Histologic severity (fibrosis, parenchymal degeneration/necrosis, hepatocyte regeneration and inflammation) was significantly higher in patients when either Mallory bodies (p < 0.0001) or cytokeratin antigen (p = 0.0021) was present in hepatocytes. Demonstration of cytokeratin antigen in hepatocytes which contained Mallory bodies correlated positively (p = 0.03) with clinical severity of the liver disease as determined by high serum bilirubin and prolonged prothrombin time (Maddrey’s discriminant function). This study suggests that (i) vitamin A deficiency may be a triggering factor in aggregation of cytokeratin filaments, and (ii) the degree of aggregation of cytokeratin may determine the histologic severity and thereby the prognosis of patients with alcoholic liver disease.