Genetic heterogeneity of hepatitis C virus and its clinical significance

Abstract

SUMMARY
The hepatitis C virus (HCV) displays high genetic heterogeneity.
Many classification systems have been used but
the most widely accepted is that of Simmonds with 11 genotypes
and 80 subtypes. Techniques used to determine the
HCV genotype are molecular biology based (genotyping
techniques) and serological (serotyping techniques). This
viral diversity has epidemiological and clinical implications
and has been associated with the severity of liver disease,
prognosis, diagnostic tests, response to treatment and failure
to generate an effective protective vaccine. Commercially
available HCV RNA reverse transcription/PCR qualitative
and quantitative first-generation assays underestimated
the HCV RNA level of genotypes 2 to 6. The second
generation methods have corrected this problem. HCV genotype
1b is the predominant genotype in Western Europe
and has been associated with a more severe clinical course
of liver disease, cirrhosis and hepatocellular carcinoma.
Genotypes 1 and 4 have been associated with a low response
rate to IFN-á ¯r to the combination of ribavirin and IFN-á®
Consequently, the duration of treatment has been tailored
according to genotype and viral load. Explaining the possible
pathogenetic mechanisms involved in the different clinical
profiles of HCV genotypes has been the subject of many
studies. HCV circulates as a mixed population of HCV
molecules termed quasispecies derived from multiple point
mutations. Multiple quasispecies have been implicated in
both chronic and acute HCV infection leading to severe
prognosis and to the evolution to chronicity respectively. Key words: Hepatitis C virus, genotypes, subtypes, geographical
distribution, quasispecies