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Hepatitis C Virus and Apoptosis: The Role of Fas (Apo-1/CD95) In Chronic Hepatitis C Virus Infection and Related Liver Diseases.

1Raghda Z Talaat, 2Desoky E Abou Ammo, 3Mona A. H. Shehata.

1Microbiology, 2Clinical Pathology, 3Tropical Medicine Departments Tanta University.

In hepatitis C virus (HCV) infection, mechanisms responsible for liver cell damage are still poorly understood and both necrosis and apoptosis (programmed cell death) may be operative. The study of the molecular mechanisms by which liver injury is induced in HCV infection might lead to design new approaches by which HCV infection can be controlled. In this work, we estimated hepatic tissue expression of Fas(Apo-1/CD95) receptor at mRNA level as a main cell death receptor that triggers apoptosis (using reverse transcription polymerase chain reaction (RT-PCR), in relation to the measurement of serum soluble Fas (sFas) that seems to inhibit apoptosis in vitro (using Enzyme Linked Immunosorbent Assay (ELISA) ). The study was conducted on 59 HCV infected patients included in three groups; chronic hepatitis (n=15) , liver cirrhosis (n=30) and hepatocellular carcinoma (HCC) (n=14). In addition, ten apparently healthy subjects served as controls. The results showed a significant increase in tissue Fas mRNA and sFas in HCV infected patients groups as compared to controls, with the highest values being found in HCC group. The liver cirrhosis group, showed significant increase in hepatic expression of Fas mRNA (detected in Child’s A cirrhotic patients) with no significant difference in serum sFas values as compared to chronic hepatitis group. Hepatic expression of Fas mRNA correlated significantly with serum sFas in HCV infected patients groups. In chronic hepatitis patients both tissue Fas mRNA and serum sFas showed significant positive correlation with the severity of necro inflammatory activity grade, while no correlation was found with serum transaminases (ALT, AST) in all patients groups. In cirrhotic patients serum sFas was increased in accordance with the advance in Child’s grade (A, B, C,). Interestingly, it was noticed that tissue Fas mRNA and serum sFas in HCV related HCC were significantly decreased in grade III with poor cell differentiation compared to grade IandII. It is concluded that Fas mediated apoptosis may play an important role in the immune mediated liver cell injury in HCV infection, and this type of reaction may occur in the absence of significant serum transaminases elevation. Moreover, cancer cells in HCV related HCC at a low differentiation level may escape from Fas mediated apoptosis.