Quasispecies of hepatitis C virus in serum and in three different parts of the liver of patients with chronic hepatitis.

Hepatitis C virus (HCV) has been known to infect hosts as a quasispecies. Several reports have shown this using serum samples, but there is little information about quasispecies in the liver. In this study, we evaluated quasispecies in serum and in 3 different parts of the liver in 8 patients with varying severity of chronic hepatitis C by calculating nucleotide diversity, entropy, type of substitution and by phylogenetic analysis. Nucleotide diversity of HCV was different in each sample and ranged from 0.37% +/- 0.31% to 4.10% +/- 1.06%. However, the degree of HCV diversity in serum correlated with that in the liver in each patient (P <.01). Common HCV clones were found both in serum and liver samples in all 6 noncirrhotic patients, but all serum clones were different from the clones from the 2 cirrhotic livers. Phylogenetic analysis showed that the degree of genetic diversity of HCV among the 3 liver samples was significantly high in the 4 patients with fibrosis. These genetic compartmentalizations of HCV did not depend on the type of substitution or the viral load of each liver sample. HCV quasispecies within the liver may be closely related to the viral life cycle and the pathogenesis of persistent infection of HCV.