Longitudinal analysis of hepatitis C virus replication and liver fibrosis progression in renal transplant recipients

The pathogenesis of hepatitis C virus (HCV) infection was investigated by a nalysis of changes in viral and histologic parameters in 36 renal transplan t recipients who were infected with HCV before transplantation. Each patien t was classified according to development of liver fibrosis as assessed by 2 liver biopsies done 35 and 81 months after transplantation: 13 had progre ssing liver fibrosis (fibrosers) and 23 did not (nonfibrosers). All develop ed high-titer posttransplant viremia with a significant increase of 1.2 log RNA copies/mL, There were no significant differences in the increases in s erum HCV RNA or genotype distributions in fibrosers and nonfibrosers, The h ypervariable region (HVR)-1 of the HCV genome was analyzed by cloning and s equencing 20 clones per sample from 5 fibrosers and 5 nonfibrosers, Compari son of samples revealed that liver fibrosis progression was significantly a ssociated with slower HVR-1 quasispecies diversification, suggesting the se lection of more aggressive variants in fibrosers.