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.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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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