Liver biopsy specimens were examined immunohistochemically to clarify structural changes of the hepatic lobules in chronic liver diseases. In normal liver carbohydrate antigen 19-9 was located in the biliary ductular epithelium, whereas factor VIII-related antigen was observed in the endothelium of portal veins, hepatic arteries, and central veins. This antigen was not detected in the sinusoidal endothelium. In contrasts, monoclonal antibody OKM5 was reactive with the sinusoidal endothelium but was unreactive with the endothelium of the portal blood vessels or central veins. In chronic active hepatitis and liver cirrhosis, both carbohydrate antigen 19-9 positive biliary ductular cells and factor VIII-related antigen positive endothelial cells were not only observed in the enlarged portal area but also extended into the parenchyma. They were occasionally accompanied by fibers. These findings suggest that fibrosis, ductular epithelial, and blood vascular proliferation in the portal space and their invasion into the parenchyma might gradually cause structural changes of the hepatic lobules in chronic liver disease.
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