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Amino Acid Substitution in HCV Core Region and Genetic Variation near the IL28B Gene Affect Viral Dynamics during Telaprevir, Peginterferon and Ribavirin Treatment

Authors
  • Akuta, Norio
  • Suzuki, Fumitaka
  • Hirakawa, Miharu
  • Kawamura, Yusuke
  • Yatsuji, Hiromi
  • 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
Jun 08, 2012
Volume
55
Issue
6
Pages
417–425
Identifiers
DOI: 10.1159/000323526
PMID: 21325786
Source
Karger
Keywords
License
Green
External links

Abstract

Objectives: Genetic variation near the IL28B gene and substitution of aa 70 and 91 in the core region of HCV-1b are useful as predictors of treatment efficacy to telaprevir/pegylated interferon (PEG-IFN)/ribavirin, but its impact on viral dynamics is not clear. Methods: This study investigated predictive factors of viral dynamics during 12- or 24-week regimen of triple therapy in 80 Japanese adults infected with HCV-1b. Results: After 24 h of commencement of treatment, the proportion of patients with Arg70 and Leu91 substitutions in the core region who showed ≥3.0 log drop in HCV RNA level was significantly higher than that of patients with Gln70 (His70) and/or Met91. At 8 and 12 weeks, HCV RNA loss rate of patients with rs8099917 genotype TT near IL28B gene was significantly higher than that of patients with non-TT. Multivariate analysis identified substitution of aa 70 and 91 as a predictor of ≥3.0 log fall in HCV RNA level at 24 h (Arg70 and Leu91) and SVR (Arg70), and rs8099917 (TT) as a predictor of HCV RNA loss at 12 weeks and SVR. Conclusions: This study identified genetic variation near IL28B gene and aa substitution of the core region as predictors of viral dynamics during triple therapy.

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