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

Yano,Yoshihiko; Seo,Yasushi; Miki,Akira; Saito,Masaya; Kato,Hirotaka; Hamano,Ken-Ichi; Oya,Manabu; Ouchi,Sachiko; Fujisawa,Takashi; Yamada,Hajime; Yamashita,Yukimasa; Tani,Satoshi; Hirohata,Shigeya; Yoon,Seitetsu; Kitajima,Naoto; Kitagaki,Kazunari; Kawara,Akira; Nakashima,Takatoshi; Yu,Hosai; Maeda,Tetsuo; Azuma,Takeshi; El-Shamy,Ahmed; Hotta,Hak; Hayashi,Yoshitake; Hepatitis Therapeutic Group,Kobe

doi:10.3892/ijmm.2012.1093

November 2012 Volume 30 Issue 5

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November 2012 Volume 30 Issue 5

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Article

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
View Affiliations / Copyright

Affiliations: Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan, Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan, Kato Clinic, Kobe, Japan, Hamano Clinic, Kobe, Japan, Division of Internal Medicine, Shin-Suma Hospital, Kobe, Japan, Division of Internal Medicine, Steel Memorial Hirohata Hospital, Kobe, Japan, Division of Internal Medicine, Kakogawa West City Hospital, Kobe, Japan, Department of Gastroenterology, Shinko Hospital, Kobe, Japan, Department of Gastroenterology, Kobe City Hospital Organization, Kobe City Medical Center West Hospital, Kobe, Japan, Division of Internal Medicine, Konan Hospital, Kobe, Japan, Department of Gastroenterology, Hyogo Prefectural Kakogawa Medical Center, Kobe, Japan, Division of Internal Medicine, Kasai City Hospital, Kobe, Japan, Kawara Clinic, Kobe, Japan, Department of Gastroenterology, Akashi Medical Center, Kobe, Japan, Division of Internal Medicine, National Hospital Organization, Kobe Medical Center, Kobe, Japan, Division of Internal Medicine, Kawasaki Hospital, Kobe, Japan, Department of Microbiology, Kobe University Graduate School of Medicine, Kobe, Japan
Pages: 1048-1052
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Published online on: August 9, 2012

https://doi.org/10.3892/ijmm.2012.1093
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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