Amino Acid Substitution in the Core Protein has no Impact on Relapse in Hepatitis C Genotype 1 Patients Treated With Peginterferon and Ribavirin

作者：Inoue Yuko; Hiramatsu Naoki^*; Oze Tsugiko; Yakushijin Takayuki; Mochizuki Kiyoshi; Fukuda Kazuto; Mita Eiji; Haruna Yoshimichi; Inoue Atsuo; Imai Yasuharu; Hosui Atsushi; Miyagi Takuya; Yoshida Yuichi; Tatsumi Tomohide; Kiso Shinichi; Kanto Tatsuya; Kasahara Akinori; Takehara Tetsuo; Hayashi Norio

来源：Journal of Medical Virology, 2011, 83(3): 419-427.

DOI：10.1002/jmv.21975

• amino acid substitution
• core protein
• hepatitis C virus
• peginterferon and ribavirin combination therapy
• relapse

Previous reports demonstrated that amino acid (aa) substitutions in the hepatitis C virus (HCV) core protein are predictors of non-virological responses to pegylated interferon (Peg-IFN) and ribavirin combination therapy. The aim of this study was to investigate the impact of core aa substitutions on viral kinetics during the treatment and relapse after the treatment. The 187 patients with HCV genotype 1 enrolled in this study were categorized into four groups according to core aa substitution patterns: double-wild group (n=92), Arg70/Leu91; 70-mutant group (n=42), GIn70/Leu91; 91-mutant group (n = 31), Arg70/Met91; and double-mutant group (n = 22), GIn70/Met91. The relationship between the core aa substitutions and the virological response was examined. Multivariate logistic regression analyses showed that substitution at aa 70 was significantly associated with a poor virological response during the first 12 weeks (decline of <1 log from baseline at week 4, <2 log at week 12), and substitution at aa 91 was significantly associated with detectable HCV RNA at week 24. With respect to relapse, only the ribavirin exposure (odds ratio (OR), 0.77; 95% confidence interval (Cl), 0.60-0.98) and HCV RNA disappearance between weeks 13 and 24 (OR, 23.69; 95% Cl, 5.44-103.08) were associated independently with relapse, with no correlation being found with the core aa substitutions and relapse. In conclusion, the results showed that core aa substitutions can be strong predictive factors at pretreatment of the non-response, but not for relapse, for virological responders with HCV RNA disappearance during treatment. J. Med. ViroL 83:419-427, 2011.

• 出版日期2011-3