Mutations in non-structural 5A and rapid viral response to pegylated interferon-α-2b plus ribavirin therapy are associated with therapeutic efficacy in patients with genotype 1b chronic hepatitis C

  • Authors: Yoshihiko Yano, Yasushi Seo, Akira Miki, Masaya Saito, Hirotaka Kato, Ken-Ichi Hamano, Manabu Oya, Sachiko Ouchi, Takashi Fujisawa, Hajime Yamada, Yukimasa Yamashita, Satoshi Tani, Shigeya Hirohata, Seitetsu Yoon, Naoto Kitajima, Kazunari Kitagaki, Akira Kawara, Takatoshi Nakashima, Hosai Yu, Tetsuo Maeda, Takeshi Azuma, Ahmed El-Shamy, Hak Hotta, Yoshitake Hayashi, Kobe Hepatitis Therapeutic Group
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  • Published online on: Thursday, August 9, 2012
  • Pages: 1048-1052
  • DOI: 10.3892/ijmm.2012.1093

Abstract

For patients chronically infected with hepatitis C virus (HCV), mutations in the non-structural 5A (NS5A) gene are important predictive factors for the response to interferon (IFN) therapy. In the present study, factor analysis of the therapeutic response of patients following pegylated IFN and ribavirin combination therapy was assessed in a multicenter study. Chronic HCV-infected patients with genotype 1b and high viral load (n=96, mean age 56.5 years; 59 males, 68 females) treated with pegylated IFN-α-2b and ribavirin combination therapy were enrolled. This study was conducted at Kobe University Hospital and 25 affiliated hospitals in Hyogo prefecture. Sixty-five patients (68%) completed treatment with both pegylated IFN and ribavirin at >80% of the weight-based scheduled dosages. Patients who reduced or terminated therapy were frequently aged women (mean age 60.8 years; 11 males, 17 females). Overall, a sustained viral response (SVR) was achieved in 42 (44%) patients out of 96. Based on per-protocol-based (PPB) analysis, the SVR rate in patients with ≥6 amino acid (aa) mutations in the IFN resistance-determining region (IRRDR) (75%) or ≥1 aa mutation in the IFN sensitivity-determining region (ISDR) (61%) was significantly higher than that in patients with <5 aa mutations in IRRDR (30%) or no mutation in ISDR (29%). Multivariate analysis revealed that rapid viral response (RVR) (odds ratio, 18.1) and mutations of ≥6 in IRRDR (odds ratio, 15.5) were significantly associated with SVR. In conclusion, mutations in the NS5A region, particularly in patients with ≥6 aa mutations in IRRDR were strongly associated with a therapeutic response to pegylated IFN and ribavirin combination therapy.
Journal Cover

November 2012
Volume 30 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

2012 Impact Factor: 1.957
Ranked #26/121 Medicine Research and Experimental
(total number of cites)

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APA
Yano, Y., Seo, Y., Miki, A., Saito, M., Kato, H., Hamano, K., Oya, M., Ouchi, S., Fujisawa, T., Yamada, H., Yamashita, Y., Tani, S., Hirohata, S., Yoon, S., Kitajima, N., Kitagaki, K., Kawara, A., Nakashima, T., Yu, H., Maeda, T., Azuma, T., El-Shamy, A., Hotta, H., Hayashi, Y., & Hepatitis Therapeutic Group, K. (2012). Mutations in non-structural 5A and rapid viral response to pegylated interferon-α-2b plus ribavirin therapy are associated with therapeutic efficacy in patients with genotype 1b chronic hepatitis C. International Journal of Molecular Medicine, 30(5), 1048-1052.
MLA
Yano, Seo, Miki, Saito, Kato, Hamano, Oya, Ouchi, Fujisawa, Yamada, Yamashita, Tani, Hirohata, Yoon, Kitajima, Kitagaki, Kawara, Nakashima, Yu, Maeda, Azuma, El-Shamy, Hotta, Hayashi, and Kobe Hepatitis Therapeutic Group. "Mutations in non-structural 5A and rapid viral response to pegylated interferon-α-2b plus ribavirin therapy are associated with therapeutic efficacy in patients with genotype 1b chronic hepatitis C." International Journal of Molecular Medicine International Journal of Molecular Medicine 30.5 (2012): 1048-1052.
Chicago
Yano, Seo, Miki, Saito, Kato, Hamano, Oya, Ouchi, Fujisawa, Yamada, Yamashita, Tani, Hirohata, Yoon, Kitajima, Kitagaki, Kawara, Nakashima, Yu, Maeda, Azuma, El-Shamy, Hotta, Hayashi, and Kobe Hepatitis Therapeutic Group. "Mutations in non-structural 5A and rapid viral response to pegylated interferon-α-2b plus ribavirin therapy are associated with therapeutic efficacy in patients with genotype 1b chronic hepatitis C." International Journal of Molecular Medicine International Journal of Molecular Medicine 30 no. 5 (2012): 1048-1052.