The role of the tumor necrosis factor (TNF)--Fas L and HCV in the development of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major public health problem in Egypt due to the high prevalence of hepatitis C viral (HCV) infection. The mechanism by which HCV exerts its carcinogenic effect on the liver is not yet understood. Previous research has suggested that perturbations of the Fas-Fas L tumor necrosis system could result in uncontrolled cancerous cell growth in the liver. This study aims to assess the relationship of Fas ligand (Fas L) to HCC. A total of 28 cases (HCC) and 56 controls (28 cirrhosis and 28 chronic hepatitis) were included in the study. Sera and tissue biopsies were tested for HCV antibody and HCV-RNA. Fas ligand expression in tissue was examined immunohistochemically using a rabbit purified polyclonal antibody. Levels of soluble Fas L were determined in serum by ELISA. The HCC cases were graded as: 17.9% Grade I, 32.1% Grade II, 35.7% Grade III and 14.3% were Grade IV. Among the cases, 81% had evidence of cirrhosis. All the cases and controls were positive for HCV-RNA. Tissue and serum PCR results were identical within the same subjects. Fas ligand cytoplasmic expression was more pronounced in HCC than in cirrhosis, and in cirrhosis more than in chronic hepatitis. This expression was higher with increasing grades of malignancy and in tissues adjacent to the tumor, than in those without nearby tumor. Soluble Fas L levels were higher in cases than in controls, with similar results as that of immunohistochemical expression. These results suggest that HCV and Fas ligand play a key role in hepatocarcinogenesis, consistent with the hypothesis that HCV induces overexpression of Fas ligand in the liver cells, resulting in escape from killing by the immune system cells, with subsequent uncontrolled growth of tissue and the development of malignancy.