HCV genotypes - role in pathogenesis of disease and response to therapy

Hepatitis C virus (HCV) shows considerable variation in its genomic structu re, allowing classification into six main genotypes. Epidemiological studie s have shown marked differences in genotype distribution by geographical re gion, and between patient groups. Improved understanding of the rate of nuc leotide sequence mutation in HCV has allowed the approximate time of diverg ence of major genotypes to be estimated, and the origin and spread of the p resent epidemic of hepatitis C to be better defined. Improved methods of ge notype definition over the last few years have enabled the importance of ge notype in the progression of HCV-related disease and response to anti-viral therapy to be studied. Present data strongly indicates that HCV genotype i s an important determinant of response to treatment, but the effect of geno type on disease progression has been harder to clarify. This is largely due to the absence of model systems of HCV infection, the epidemiological diff erences in patient groups infected with the different genotypes, and the la ck of good prospective longitudinal clinical data. As a result of advances in methodology, and recent results of large clinical trials of combination therapy, a knowledge of HCV genotype is now central to the clinician in the management of patients with chronic hepatitis C.