Fas antigen in serum and liver tissue of patients with chronic hepatitis C

ABSTRACT

Fas [APO-1/CD95], a member of the tumor necrosis factor receptor Family, can mediate apoptosis when engaged by its ligand or by anti-Fas antibody. Fas is upregulated on the surface of hepatocytes in patients with a variety of liver pathologies, including hepatitis, alcoholic cirrhosis, and acute liver failure. Moreover, expression of Fas ligand is substantially upregulated, in areas of lymphocytic infiltration, in liver diseases, suggesting Fas/FasL interactions may mediate liver damage in humans. The purpose of this study was to evaluate the relationship of serum soluble Fas [sFas] levels and hepatic Fas antigen expression with the degree of hepatic inflammatory activity in patients with chronic hepatitis C infection. The effect of concomitant schistosomiasis, as an endemic liver disease in Egypt, on serum and liver Fas expression was also studied. Serum sFas levels were measured by enzyme-linked immunosorbant assay in 69 chronic hepatitis C patients; 16 of them were under 18 years and compared with those in normal volunteers, and patients with chronic HBV infection. The results of serum tests were compared with ALT levels. HCV-RNA titer, histological inflammatory activity, and Fas expression in liver biopsies. The effect of combined HCV infection and schistosomal infestation on serum sFas and tissue Fas expression was also studied. Serum sFas and tissue Fas expression were then evaluated with each components of histological inflammatory activity scoring system [modified Knodell's HAI]. Serum sFas levels in chronic hepatitis C patients were significantly higher than those in normal volunteers [p<0.001]. They showed no difference from those in patients with chronic HBV infection [p>0.05]. Hepatic schistosomiasis didn't affect serum sFas levels or tissue expression of Fas antigen in chronic hepatitis C patients. Histologically, serum sFas levels showed strong correlation with tissue Fas expression [p<0.001] and with the degree of hepatic inflammatory activity [p<0.01]. Likewise, tissue Fas expression correlated with the degree of histological inflammatory activity [p<0.05]. Moreover, positive correlation was found between serum sFas and tissue Fas expression and the degree of interface hepatitis [piecemeal necrosis] in chronic hepatitis C patients with mild [p<0.01] and moderate and severe activity [p<0.05]. However, no correlation was observed between serum sFas and serum ALT levels. Also, no correlation was observed between HCV-RNA titer and sFas levels or tissue Fas expression. Our findings suggest that serum sFas levels may reflect the expression of Fas antigen on hepatocytes and the severity of liver inflammation in chronic hepatitis C and may be used as a serological indicator of histological inflammatory activity. They also support the concept that immune-mediated apoptosis may play a crucial role in the pathogenesis of chronic hepatitis C. Hepatic schistosomiasis seems to have no impact on serum sFas levels or hepatic tissue Fas expression