ABSTRACT
To determine the role of CD8+ T-cell responses and apoptosis in mediating liver injury in chronic hepatitis C, an analysis of cytotoxic CD8+ T-cell and apoptosis markers was performed in 70 patients with proven chronic hepatitis C and 30 controls. CD8+ T-cell responses to a panel of HCV proteins and peptides were performed in an Elispot assay. Apoptosis was detected by peripheral expression of Fas, Fas ligand and perforin as well as apoptosis of hepatocytes was also detected using transferase-mediated immunohistochemical d-UTP biotin nick labeling [TUNEL] and flowcytometry. Cytotoxic HLA A2 restricted responses were detected in 54 patients. The expression of Fas antigen, Fas ligand and perforin was significantly increased in patients compared with the control subjects. Immunohistochemical intracytoplasmic Fas expression and the apoptosis index of hepatocytes directly correlated to the necroinflammatory activity in the liver. A direct significant correlation was detected between the CD8+ T-cell responses and the apoptosis index. These results indicated that HCV- specific CD8+ T-cell responses and apoptosis can be detected in the majority of patients with chronic HCV and liver injury in chronic HCV is mediated through these responses