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We have investigated the localization of HCV in the liver and the expression of Fas antigen, involved in hepatocellular death through apoptosis, to examine the relation between HCV infection and Fas antigen cellular expression. The localization of HCV was investigated by in situ hybridization (ISH), and the expression of Fas antigen was determined by immunohistochemistry using an anti-Fas monoclonal antibody, in 20 surgically-resected liver specimens from anti-HCV positive patients. The Methylgreen/Pyronin Y technique clearly showed well-preserved tissue RNA in 8 of 20 livers. ISH determined the co-localization of signals for plus and minus strands of HCV-RNA in the cytoplasm of hepatocytes. Fas antigen was more strongly expressed on the plasma membrane of the periportal hepatocytes than on the plasma membrane of the centrilobular hepatocytes, even when HCV-RNA was found to be widely distributed in the hepatocytes throughout the liver lobule. Furthermore, Fas antigen positive hepatocytes were frequently observed close to the area of piecemeal necrosis associated with a high incidence of apoptosis. The results suggested that the expression of Fas antigen does not occur by HCV infection alone, but probably requires several other factors.

The Localization of HCV and the Expression of Fas Antigen in the Liver of HCV-related Chronic Liver Disease.