Alcoholic hepatitis is characterized by hepatocyte necrosis associated with infiltration of the liver parenchyma by neutrophils. The mechanisms responsible for recruiting neutrophils to the liver are unknown. We report high circulating levels and tissue expression of the endothelial adhesion molecule E-selectin in alcoholic hepatitis. Because expression of E-selectin is involved in neutrophil transmigration into inflamed tissue, it may play a crucial role in the recruitment of neutrophils to the liver in alcoholic hepatitis. By contrast, we detected high levels of vascular cell adhesion molecule-1, the endothelial counter-receptor for the lymphocyte adhesion molecule very late antigen-4, in alcoholic cirrhosis, which is associated with a predominantly mononuclear cell infiltrate. Both diseases were associated with high levels of circulating intercellular adhesion molecule-1, which is released by activated lymphocytes, providing further evidence of immune activation in alcoholic liver disease. (HEPA-TOLOGY 1994;19:588-594.)
The two major liver diseases associated with excess alcohol ingestion can be distinguished by different inflammatory processes. In alcoholic hepatitis there is an intense infiltration of inflammatory cells, particularly neutrophils, which are associated with areas of hepatocellular necrosis (1). Rapid progression to liver failure, which carries high mortality, is frequently seen, even after cessation of alcohol ingestion (2,3). It seems likely that neutrophils are involved in the liver damage of alcoholic hepatitis; circulating neutrophils are activated, and those infiltrating the liver express increased levels of p2 integrins. This would allow them to interact with the adhesion ligand intercellular adhesion molecule-1 (ICAM-11, which is induced on hepatocytes in alcoholic hepatitis, (4, 5). Furthermore, alcoholic hepatitis is