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The clinicopathologic relevance of the hepatic expression of Lewis Y (Le(y)), a carbohydrate antigen, and its plasma levels was studied in benign and malignant liver diseases. Tissue and plasma antigens, respectively, were determined with an avidin-biotin-peroxidase complex method and a radioimmunoassay using monoclonal antibody AH6. Normal liver cells and bile ductules did not express Le(y). In the inflammatory tissues, the liver cells and proliferated bile ductules expressed Le(y). The strongest expression by the liver cells was observed in chronic active hepatitis with severe activity and that by the ductules in liver cirrhosis. Only 1 of 16 hepatocellular carcinomas expressed Le(y). The plasma levels of Le(y) increased significantly but nonspecifically in chronic persistent hepatitis, chronic active hepatitis, liver cirrhosis, and hepatocellular carcinomas. It was concluded that (1) Le(y) is an inflammation-associated but not a cancer-associated antigen; (2) the more the tissue damage advances, the more the antigen is expressed; and (3) hepatic and plasma Le(y) are, however, nonspecific markers of necroinflammatory liver diseases.