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The effect of Antiviral therapy on HCV genotype

V Tedeschi1, K Mahaney W, H ConjeevaramW, G Maertens3, M Beames W, J Vergalla W, JH HoofnagleW, and R SallieW Division of Gastroenterology, Georgetown University1, Liver Diseases SectionW, NIDDK, NIH, Bethesda, MD, 20892, and Innogenetics, Zwijnaarde, Belgium.

Hepatitis C virus (HCV) exists as several well characterised and distinct genotypes which may influence the severity of liver disease, the response to therapy and the development of emergent treatment-resistant strains. In patients infected with multiple genotypes it is possible differing replicative efficiencies may cause one genotype to predominate over the others. The aim of this study was to examine the influence of antiviral therapy on the HCV genotypes, and in particular, to correlate the emergence of genotypes with biochemical, histological and virological variables.

PCR amplified HCV RNA from paired serum samples obtained before and after therapy from patients (n=99) with chronic HCV enrolled in placebo controlled trials of interferon (IFN, n=42) and ribavirin (n=58) were genotyped by Line Probe Assay (LiPA). Serum HCV RNA was quantitated by bDNA assay, and clinical and histological response was defined according to standard criteria.

Infection with multiple HCV genotypes was detected in 7 patients (5 before therapy, 2 after). HCV RNA was undetectable 1 year following cessation of IFN in 8 cases. Treatment with IFN (but not ribavirin) resulted in suppression of one genotype in all 5 multiply infected cases, wheras emergence of multiple genotypes was seen in 2 IFN treated cases following unsuccesful (non/partial responders) therapy. Neither emergence nor suppression of genotypes was predicted by viral levels, histology, initial genotype or presumed source of infection.

In stable, chronic HCV infected patients presence of multiple HCV genotypes is more common than may be apparent from genotyping assays performed at one timepoint. Suppression of viral replication by IFN in patients infected with multiple types does not appear to be genotype specific.

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