Influence of liver hepatitis C virus RNA and hepatitis C virus genotype onFas-mediated apoptosis after liver transplantation for hepatitis C

Background. Recurrent hepatitis C virus (HCV) infection after liver transpl antation is characterized by a high level of intrahepatic HCV replication a nd more severe liver damage in case of genotype Ib infection. We investigat ed the involvement of apoptosis in recurrent HCV liver disease, and its pos sible links with histological findings, HCV genotype, liver HCV RNA level, and liver Fas mRNA level. Methods. We studied 61 liver graft biopsy specimens from 25 patients transp lanted for HCV-related cirrhosis. DNA fragmentation was determined semi-qua ntitatively by in situ end labeling. HCV RNA and liver Fas mRNA were determ ined in parallel by quantitative polymerase chain reaction, with ribosomal 285 RNA as internal standard. Results. Apoptotic lesions were predominantly portal (nonhepatocytic) or lo bular (hepatocytic). Both were correlated with serum aminotransferase level s. The degree of portal apoptosis correlated with acute rejection (P < 0.00 1), although lobular apoptosis was associated with lobular hepatitis (P < 0 ,02), and HCV genotype Ib (P = 0.04), In multivariate analysis, liver Fas m RNA level independently correlated with HCV-related chronic active hepatiti s (P = 0.04), age (P = 0.01), and liver HCV RNA level (P = 0.0007). Conclusions. After liver transplantation, 1) apoptosis is involved in HCV-r elated liver damage; 2) HCV type Ib may induce more severe apoptotic lesion s than other genotypes; and 3) Fas transcription may be upregulated by intr ahepatic HCV replication.