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Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: a Japanese multi-center study

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Chronic hepatitis C (CHC) genotype 1b patients with high viral load are resistant to peginterferon (PEG-IFN) and ribavirin (RBV) combination therapy, especially older and female patients.

Methods

To elucidate the factors affecting early and sustained viral responses (EVR and SVR), 409 genotype 1b patients CHC with high viral loads who had received 48 weeks of PEG-IFN/RBV therapy were enrolled. The amino acid (aa) sequences of the HCV core at positions 70 and 91 and of the interferon sensitivity determining region (ISDR) were analyzed. Host factors, viral factors, and treatment-related factors were subjected to multivariate analysis.

Results

Male gender, low HCV RNA load, high platelet count, two or more aa mutations of ISDR, and wild type of core aa 70 were independent predictive factors for SVR. In patients with over 80% adherences to both PEG-IFN and RBV, male gender, mild fibrosis stage, and wild type of core aa 70 were independent predictors for SVR.

Conclusions

Independent predictive factors for SVR were: no aa substitution at core aa 70, two or more aa mutations in the ISDR, low viral load, high values of platelet count, mild liver fibrosis and male gender.

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Abbreviations

CHC:

Chronic hepatitis C

PEG-IFN:

Peginterferon

RBV:

Ribavirin

RVR:

Rapid viral response

cEVR:

Complete early viral response

LVR:

Late viral response

ETR:

End of treatment response

NR:

Non response

SVR:

Sustained viral response

ISDR:

Interferon sensitivity determining region

Aa:

Amino acid

ALT:

Alanine aminotransferase

PLT:

Platelet

HCC:

Hepatocellular carcinoma

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Acknowledgments

We express our thanks to other members of the Study Group of Optimal Treatment of Viral Hepatitis; Hideyuki Nomura, Shin-Kokura Hospital; Yoshiyuki Ueno, University of Tohoku; Hisataka Moriwaki, Gifu University; Makoto Oketani, Kagoshima University Graduate School of Medical and Dental Sciences; Masataka Seike, Oita University; Hiroshi Yotsuyanagi, The University of Tokyo. This study was supported in part by a Grant-in-Aid from the Ministry of Health, Labor and Welfare, Japan.

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Authors and Affiliations

  1. Hepatology Center, Saiseikai Suita Hospital, 1-2 Kawazonocho, Suita, 564-0013, Japan

    Takeshi Okanoue

  2. Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji Kamigyo-Ku, Kyoto, 602-8566, Japan

    Takeshi Okanoue, Yoshito Itoh, Hiroaki Hashimoto, Kohichiroh Yasui & Masahito Minami

  3. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan

    Tetsuo Takehara

  4. Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Eiji Tanaka

  5. Department of Gastroenterology, Ehime University, 454 Shizukawa, Tohon, Ehime, 791-0295, Japan

    Morikazu Onji

  6. Departmet of Gastroenterology, Sapporo-Kosei General Hospital, Kita Sanjyo, Chuo-ku, Sapporo, 060-0033, Japan

    Joji Toyota

  7. Department of Medicine and Molecular Science, Graduate School of Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan

    Kazuaki Chayama

  8. Department of Hepato-Biliary-Pancreas, Fujita Health Science, Kutsukake-cho, Toyoake, 470-1192, Japan

    Kentaro Yoshioka

  9. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Sakaiminamimachi, Musashino, 180-8610, Japan

    Namiki Izumi

  10. Department of Hepatology, Toranomon Hospital, Kajigaya, Takatsu-ku, Kawasaki, 213-8587, Japan

    Norio Akuta & Hiromitsu Kumada

Authors
  1. Takeshi Okanoue
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  2. Yoshito Itoh
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  3. Hiroaki Hashimoto
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  8. Morikazu Onji
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  12. Namiki Izumi
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  13. Norio Akuta
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  14. Hiromitsu Kumada
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Correspondence to Takeshi Okanoue.

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Okanoue, T., Itoh, Y., Hashimoto, H. et al. Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: a Japanese multi-center study. J Gastroenterol 44, 952–963 (2009). https://doi.org/10.1007/s00535-009-0087-x

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  • DOI: https://doi.org/10.1007/s00535-009-0087-x

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