Hepatitis C virus kinetics by administration of pegylated interferon-α in human and chimeric mice carrying human hepatocytes with variants of the IL28B gene
نویسندگان
چکیده
OBJECTIVE Recent studies have demonstrated that genetic polymorphisms near the IL28B gene are associated with the clinical outcome of pegylated interferon α (peg-IFN-α) plus ribavirin therapy for patients with chronic hepatitis C virus (HCV). However, it is unclear whether genetic variations near the IL28B gene influence hepatic interferon (IFN)-stimulated gene (ISG) induction or cellular immune responses, lead to the viral reduction during IFN treatment. DESIGN Changes in HCV-RNA levels before therapy, at day 1 and weeks 1, 2, 4, 8 and 12 after administering peg-IFN-α plus ribavirin were measured in 54 patients infected with HCV genotype 1. Furthermore, we prepared four lines of chimeric mice having four different lots of human hepatocytes containing various single nucleotide polymorphisms (SNP) around the IL28B gene. HCV infecting chimeric mice were subcutaneously administered with peg-IFN-α for 2 weeks. RESULTS There were significant differences in the reduction of HCV-RNA levels after peg-IFN-α plus ribavirin therapy based on the IL28B SNP rs8099917 between TT (favourable) and TG/GG (unfavourable) genotypes in patients; the first-phase viral decline slope per day and second-phase slope per week in TT genotype were significantly higher than in TG/GG genotype. On peg-IFN-α administration to chimeric mice, however, no significant difference in the median reduction of HCV-RNA levels and the induction of antiviral ISG was observed between favourable and unfavourable human hepatocyte genotypes. CONCLUSIONS As chimeric mice have the characteristic of immunodeficiency, the response to peg-IFN-α associated with the variation in IL28B alleles in chronic HCV patients would be composed of the intact immune system.
منابع مشابه
Association of IL28B Genotypes and Baseline Serum Interferon-γ-Inducible-Protein-10 Levels with Treatment Response in Hepatitis C Virus Patients in China
BACKGROUND/AIMS Several studies have demonstrated that serum interferon-γ-inducible-protein-10 (IP-10) levels at baseline and single nucleotide polymorphisms (SNPs) near the IL28B gene were associated with viral response and treatment outcomes. Our purpose was to assess the combination of pretreatment IP-10 levels with IL28B SNPs as predictors of treatment response to pegylated interferon α-2a ...
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