Relationship between hepatitis C virus genetic complexity, epidemiological, clinical and virological characteristics of hepatitis C virus-related liver disease and the biochemical and virological responses to interferon alpha in patients with chronic hepatitis C

In infected individuals, hepatitis C virus (HCV) circulates as a complex mi xing of viral populations with different genomic nucleotide sequences prese nt in various amounts. When infection becomes chronic, these populations re ach an equilibrium referred as to a <<quasispecies>> distribution of HCV vi rions. Each patient harbours his own quasispecies, which is derived from th e viral sequences present at the time of infection [1,2], The number of dis tinct viral populations in a quasispecies is referred as to the genetic "co mplexity" of the quasispecies, whereas the phylogenetic distances between t hese populations define the genetic "diversity" of the quasispecies, The emergence and the later expansion of the viral quasispecies in arl infe cted patient are likely to be the results of: - the occurrence of errors in genome replication, a consequence of the lack of "proofreading" activity of the viral RNA-dependent RNA polymerase, that causes mutations in the genome, - the later selection of certain mutated viral populations by the selective pressure of the immune response of the host. The quasispecies distribution of HCV could be the main mechanism leading to chronic infection, by generating immune escape viral mutants. The aims of this study were: - to study the relationships between HCV genetic complexity and the other p arameters of HCV infection, - to determine whether pretreatment viral complexity could influence the bi ochemical and virological responses to interferon alpha (IFN) therapy in pa tients with chronic hepatitis C.