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

作者: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
来源:Intervirology, 2012, 55(3): 231-241.
DOI:10.1159/000328327

摘要

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.