Association between HCV amino acid substitutions and outcome of peginterferon and ribavirin combination therapy in HCV genotype 1b and high viral load

作者：Toyoda Hidenori^*; Kumada Takashi; Tada Toshifumi; Arakawa Takahiro; Hayashi Kazuhiko; Honda Takashi; Katano Yoshiaki; Goto Hidemi

来源：Journal of Gastroenterology and Hepatology, 2010, 25(6): 1072-1078.

DOI：10.1111/j.1440-1746.2010.06240.x

• amino acid substitution
• chronic hepatitis C
• hepatitis C virus
• peginterferon and ribavirin therapy
• resistance to interferon

Background and Aim:
We prospectively compared the sensitivity to interferon (IFN) and the efficacy of antiviral combination therapy with peginterferon (PEG-IFN) and ribavirin for chronic hepatitis C virus (HCV) genotype 1b infection according to the amino acid sequences of the HCV core, E1, and NS5A regions reported to be associated with the outcome of antiviral therapy.
Methods:
A total of 107 patients with HCV genotype 1b were investigated. All patients received combination therapy with PEG-IFN alpha-2b and ribavirin. Amino acids 70 and 91 (core), 139 (E1), and 2209-2248 (NS5A) of HCV were analyzed by direct nucleotide sequencing.
Results:
The reduction in HCV RNA concentration at 24 h after a single administration of conventional IFN-alpha and after the start of combination therapy was significantly less marked, and rates of complete early virologic response, end-of-treatment response, and sustained virologic response (SVR) were significantly lower (all P < 0.0001) in patients with glutamine at amino acid 70 (n = 29) than in those with arginine at that position (n = 70). We found no differences associated with the other amino acid positions. Amino acid 70 was an independent factor for the responses to the therapy in multivariate analysis.
Conclusion:
The identity of amino acid 70 of the HCV core region affected the sensitivity to IFN; patients with glutamine at amino acid 70 of HCV showed resistance to IFN. Consequently, it strongly affected the outcome of combination therapy with PEG-IFN and ribavirin in Japanese patients with HCV genotype 1b.

• 出版日期2010-6