Association of interleukin 28B and mutations in the core and NS5A region of hepatitis C virus with response to peg-interferon and ribavirin therapy

Kazuhiko Hayashi, Yoshiaki Katano, Takashi Honda, Masatoshi Ishigami, Akihiro Itoh, Yoshiki Hirooka, Tetsuya Ishikawa, Isao Nakano, Kentaro Yoshioka, Hidenori Toyoda, Takashi Kumada, Hidemi Goto
Liver International: Official Journal of the International Association for the Study of the Liver 2011, 31 (9): 1359-65

BACKGROUND AND AIMS: Mutations in the core and NS5A region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. Genome-wide association studies have revealed that the single-nucleotide polymorphism (SNP) of interleukin 28B (IL28B) contributes to IFN response. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the core and NS5A region affect the response to IFN therapy.

METHODS: A total of 299 patients (157 men, 142 women; mean age, 55.9 ± 10.3 years) infected with HCV genotype 1b were studied. The fibrosis stage was diagnosed as F0 (n=23), F1 (n=121), F2 (n=62), F3 (n=32) and F4 (n=7) by liver biopsy.

RESULTS: Of the 299 patients, 138 achieved sustained virological response (SVR). On univariate analysis, predictors of SVR were age <60 years, male gender, higher platelet count, lack of fibrosis, non-Q at core 70, mutant-type interferon sensitivity-determining region (ISDR) and IL28B genotype TT. The factors related to SVR on multivariate analysis were IL28B (P=0.0001), fibrosis (P=0.0111) and mutations in the core region70 (P=0.0267) and ISDR (P=0.0408). The best SVR was achieved in patients with non-Q70, mutant-type ISDR and T allele (74.5%), and the worst was achieved in patients with Q70, wild-type ISDR and G allele (8.1%).

CONCLUSIONS: The SNP of IL28B and mutations in the core region and NS5A are associated with IFN responsiveness. Both host and viral factors might be useful for predicting IFN response.

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