Journal of Gastroenterology

, Volume 44, Issue 9, pp 952–963 | Cite as

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

  • Takeshi OkanoueEmail author
  • Yoshito Itoh
  • Hiroaki Hashimoto
  • Kohichiroh Yasui
  • Masahito Minami
  • Tetsuo Takehara
  • Eiji Tanaka
  • Morikazu Onji
  • Joji Toyota
  • Kazuaki Chayama
  • Kentaro Yoshioka
  • Namiki Izumi
  • Norio Akuta
  • Hiromitsu Kumada
Original Article—Liver, Pancreas, and Biliary Tract



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.


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.


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.


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.


Chronic hepatitis C Peginterferon and ribavirin Core amino acid Interferon sensitivity determining region 



Chronic hepatitis C






Rapid viral response


Complete early viral response


Late viral response


End of treatment response


Non response


Sustained viral response


Interferon sensitivity determining region


Amino acid


Alanine aminotransferase




Hepatocellular carcinoma



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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Copyright information

© Springer 2009

Authors and Affiliations

  • Takeshi Okanoue
    • 1
    • 2
    Email author
  • Yoshito Itoh
    • 2
  • Hiroaki Hashimoto
    • 2
  • Kohichiroh Yasui
    • 2
  • Masahito Minami
    • 2
  • Tetsuo Takehara
    • 3
  • Eiji Tanaka
    • 4
  • Morikazu Onji
    • 5
  • Joji Toyota
    • 6
  • Kazuaki Chayama
    • 7
  • Kentaro Yoshioka
    • 8
  • Namiki Izumi
    • 9
  • Norio Akuta
    • 10
  • Hiromitsu Kumada
    • 10
  1. 1.Hepatology CenterSaiseikai Suita HospitalSuitaJapan
  2. 2.Department of Gastroenterology and HepatologyKyoto Prefectural University of MedicineKyotoJapan
  3. 3.Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
  4. 4.Department of MedicineShinshu University School of MedicineMatsumotoJapan
  5. 5.Department of GastroenterologyEhime UniversityEhimeJapan
  6. 6.Departmet of GastroenterologySapporo-Kosei General HospitalSapporoJapan
  7. 7.Department of Medicine and Molecular Science, Graduate School of ScienceHiroshima UniversityHiroshimaJapan
  8. 8.Department of Hepato-Biliary-PancreasFujita Health ScienceToyoakeJapan
  9. 9.Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashinoJapan
  10. 10.Department of Hepatology, Toranomon HospitalKawasakiJapan

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