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Amino Acid Substitution in HCV Core/NS5A Region and Genetic Variation Near IL28B Gene Affect Treatment Efficacy to Interferon plus Ribavirin Combination Therapy

Authors
  • Akuta, Norio
  • Suzuki, Fumitaka
  • Hirakawa, Miharu
  • Kawamura, Yusuke
  • Sezaki, Hitomi
  • Suzuki, Yoshiyuki
  • Hosaka, Tetsuya
  • Kobayashi, Masahiro
  • Kobayashi, Mariko
  • Saitoh, Satoshi
  • Arase, Yasuji
  • Ikeda, Kenji
  • Chayama, Kazuaki
  • Nakamura, Yusuke
  • Kumada, Hiromitsu
Type
Published Article
Journal
Intervirology
Publisher
S. Karger AG
Publication Date
Jul 05, 2011
Volume
55
Issue
3
Pages
231–241
Identifiers
DOI: 10.1159/000328327
PMID: 21734353
Source
Karger
Keywords
License
Green
External links

Abstract

Objective: To evaluate predictive factors of treatment efficacy to interferon (IFN)/ribavirin in patients infected with HCV genotype 1b (HCV-1b). Methods: This study investigated pretreatment predictors, including viral- (aa substitutions in core aa 70/91 and NS5A-ISDR/IRRDR) and host-related factors (genetic variation near IL28B gene), to 48-week IFN/ribavirin in 490 Japanese adults infected with HCV-1b. Results: The proportion of patients who showed end-of-treatment response (ETR), sustained virological response (SVR), and SVR after ETR was 76, 54, and 76%, respectively. There was a significant positive correlation between the number of aa substitutions in ISDR and those in IRRDR. Concerning the substitution of core aa 91, the number of aa substitutions in ISDR/IRRDR of patients with Leu91 was significantly higher than that of patients with Met91. Furthermore, levels of viremia were influenced by aa substitutions in core aa 91 and ISDR/IRRDR. By multivariate analysis, rs8099917 genotype was an important predictor of ETR and SVR. With regard to viral factors, core aa 70/91 was an important predictor of ETR, and SVR after ETR. ISDR was an important predictor of SVR, and SVR after ETR. Conclusion: aa substitution in core/NS5A region and genetic variation near IL28B were important predictors of treatment efficacy to IFN/ribavirin.

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