Fas-mediated hepatocyte apoptosis is increased by hepatitis C virus infection and alcohol consumption, and may be associated with hepatic fibrosis: mechanisms of liver cell injury in chronic hepatitis C virus infection

Epidemiological studies have established that heavy alcohol consumption in persons with chronic hepatitis C virus (HCV) infection is associated with a dvanced liver disease, including cirrhosis. The aims of this study were to evaluate the relationship between alcohol consumption and hepatocyte apopto sis in HCV-infected patients and to determine the role of Fas in HCV-mediat ed apoptosis. Liver tissue from 44 HCV-infected patients with variable alco hol consumption, and 10 normal control subjects who did not consume alcohol was examined for hepatocyte apoptosis, proliferation and Fas expression. A lcohol consumption was assessed using the 'Lifetime Drinking History' alcoh ol questionnaire. HCV RNA, alanine aminotransferase (ALT) and ferritin were also assessed in addition to demographic data. Hepatocyte apoptosis was si gnificantly greater in HCV-infected patients compared to controls. Expressi on of Fas (CD95) was found in HCV patients but not in controls. The degree of Fas expression correlated with hepatocyte apoptosis as detected by termi nal UTP nick end labelling (TUNEL). Active ethanol consumption led to a sig nificant increase in hepatocyte apoptosis. Fas expression correlated with f ibrosis in HCV-infected patients who were not actively drinking ethanol. In summary, HCV leads to increased apoptotic cell death in hepatocytes. Progr ammed cell death can be further up-regulated by active ethanol consumption. The correlation between Fas expression and TUNEL supports the hypothesis t hat the Fas-Fas ligand interaction is the major mechanism for HCV-induced h epatocyte apoptosis.