Influence of liver hepatitis C virus RNA and hepatitis C virus genotype on FAS-mediated apoptosis after liver transplantation for hepatitis C.

Abstract

Recurrent hepatitis C virus (HCV) infection after liver transplantation is characterized by a high level of intrahepatic HCV replication and more severe liver damage in case of genotype 1b infection. We investigated the involvement of apoptosis in recurrent HCV liver disease, and its possible links with histological findings, HCV genotype, liver HCV RNA level, and liver Fas mRNA level. We studied 61 liver graft biopsy specimens from 25 patients transplanted for HCV-related cirrhosis. DNA fragmentation was determined semi-quantitatively by in situ end labeling. HCV RNA and liver Fas mRNA were determined in parallel by quantitative polymerase chain reaction, with ribosomal 28S RNA as internal standard. Apoptotic lesions were predominantly portal (nonhepatocytic) or lobular (hepatocytic). Both were correlated with serum aminotransferase levels. The degree of portal apoptosis correlated with acute rejection (P<0.001), although lobular apoptosis was associated with lobular hepatitis (P<0.02), and HCV genotype 1b (P=0.04). In multivariate analysis, liver Fas mRNA level independently correlated with HCV-related chronic active hepatitis (P=0.04), age (P=0.01), and liver HCV RNA level (P=0.0007). After liver transplantation, 1) apoptosis is involved in HCV-related liver damage; 2) HCV type 1b may induce more severe apoptotic lesions than other genotypes; and 3) Fas transcription may be up-regulated by intrahepatic HCV replication.