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- Title
Kinetic response of wild and mutant core codon 70 strains of HCV genotype 1b to pegylated interferon-α and ribavirin therapy.
- Authors
Zhongjie Hu; Ying Liu; Lixia Qiu; Zuopeng Fan; Wei Nie; Shan Liang; Ronghua Jin
- Abstract
Background: Amino acid (aa) 70 substitution (R70Q/H) in the core protein of hepatitis C virus (HCV) genotype 1b has been shown to be one of the key factors in determining resistance for pegylated interferon-α plus ribavirin combination therapy (PEG-IFNα/RBV). But the exact mechanisms remain unclear. The aim of this study was to investigate the dynamic response of wild and mutant core codon 70 strains to PEG-IFNα/RBV treatment. Methods: One hundred twelve Chinese patients with chronic HCV 1b infection were enrolled and received a standard protocol of 48 weeks of PEG-IFNα/RBV therapy and 24 consecutive weeks of follow-up. Serial blood samples were obtained at pretreatment baseline, and again at weeks 2, 4, 8, 12, and 24 during therapy for the quantification of 70R and 70Q/H strains. Dynamic characteristics and association with early virological response (EVR), sustained virological response (SVR) and IL28B genotypes were analyzed. Results: Of the 112 patients enrolled in this study, 93.8 % (105/112) were infected with mixture of 70R and 70Q/H strains before treatment. The 70Q/H strain was dominant in 20.5 % of patients. 42.9 % of patients with dominant 70Q/H exhibited EVR versus 88.6 % of patients with dominant 70R (P < 0.001). Furthermore, 35.0 % of patients with dominant 70Q/H exhibited SVR versus 77.4 % with dominant 70R (P < 0.001). However, regardless of the dominant strain, virological response types or the IL28B SNP genotypes, 70Q/H strains always exhibited the same response to treatment as the 70R strains and the percentage of HCV harboring the 70Q/H substitution did not change significantly during treatment. Conclusions: Although the ratio of 70Q/H to 70R is related to the virological response, 70Q/H strains always exhibited the same response as the 70R strains during PEG-IFNα/RBV treatment. Substitution of R70Q/H alone is not enough to lead to resistance to therapy. Positive selection for 70Q/H induced by IFNα was not observed.
- Subjects
PHENOTYPES; GENOMES; HEPATITIS C virus; GENETIC code; INFECTION
- Publication
Virology Journal, 2015, Vol 12, Issue 1, p1
- ISSN
1743-422X
- Publication type
Article
- DOI
10.1186/s12985-015-0451-9