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1995 Fiscal Year Final Research Report Summary

Interferon resistance of hepatitis C virus

Research Project

Project/Area Number 06670595
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionOkinaka Memorial Institute for Medical Study

Principal Investigator

CHAYAMA Kazuaki  Research associate Okinaka Memorial Institute for Medical Research, 研究員 (00211376)

Co-Investigator(Kenkyū-buntansha) IKEDA Kenji  Research associate Okinaka Memorial Institute for Medical Research, 研究員 (80211027)
KUMADA Hiromitsu  Research associate Okinaka Memorial Institute for Medical Research, 研究員 (20124307)
Project Period (FY) 1994 – 1995
KeywordsHepatitis C virus / amino acid sequence / ISDR / PCR
Research Abstract

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are prdictive factors of poor response to interferon therapy in patients with chronic hepatitis C.However, few patients with low virus load and genotype 1b show poor response to treatment. To further examine the factors predicting the response to interferon therapy in patients with genotype 1b infection, we analyzed entire nucleotide sequences of HCV extracted from three non-responders and one responder. We were no able to identify any single amino acid mutation which determines the resitance to interferon. We also examined 57 consecutive patients who were treated with 624 million units of lymphoblastoid alpha-interferon. Multivariate analysis showed that pretreatment virus load and multiple amino acid substitutions in the ISDR significantly correlated with failure to eliminate the virus. Our data support the hypothesis that HCV without amino acid substitution in the ISDR is resistant to interferon treatment. However, polymerase chain reaction-based analysis of two responders with multiple amino acid substitutions in the ISDR revealed the presence of a small amount of wild type strain in their serum, suggesting that the wild type HCV is not resistant to interferon. The precise mechanism of anti-viral effect of interferon and its relationship with amino acid substitutions of the ISDR should be further investigated in order to develop a more effective anti-viral strategy.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Chayama K et al.: "A pilot study of corticosteroid priming for lymphoblastoid IFN in patients with chronic hepatitis C." Hepatology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chayama K et al.: "Genotype, slow decrease in virus titer during IFN treatment and high degree of sequence variability of HVR are indicative of poor response to IFN treatment" Journal of Hepatology. 23. 648-653 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chayama K et al.: "Nucleotide sqquence of hepatitis C virus (type 3b)isolated from a Japanese patient with chronic hepatitis C" Journal of General Virology. 75. 3623-3628 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto M et al.: "Genotyping of hepatitis C virus by polymerase chain reaction : a comparison of two PCR-based methods using core or NS5 primers." International Hepatology Communications. 4. 67-71 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chayama K et al.: "High virus titer, slow virus decrease, genotype II, and sequence variability of E2/NS1 HVR predict poor response to interferon therapy in chronic hepatitis C" Viral Hepatitis and Liver Dsease. 617-620 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chayama K et al.: "A pilot study of corticosteroid priming for lymphoblastoid interferon-alpha in patients with chronic hepatitis C." Hepatology. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chayama K et al.: "Genotype, slow decrease in virus titer during interferon treatment and high degree of sequence variability of HVR are indicative of poor response interferon treatment" Journal of Hepatology. 23. 648-653 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto M et al.: "Genotyping of hepatitis C virus by polymerase chain reaction : a comparison of two PCR-based methods using core or NS5 primers" International Hepatology Communications. 4. 67-71 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chayama K et al.: "Molecular analysis of intraspousal transmission of hepatitis C virus." Journal of Hepatology. 22. 431-439 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chayama K et al.: "Nucleotide sequences of hepatitis C virus (type 3b) isolated from a Japanese patient wich chronic hepatitis C." Journal of General Virology. 75. 3623-3628 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chayama K et al.: "Antiviral effect of lymphoblastoid interferon-alpha on hepatitis C virus in patients with chronic hepatitis type C." Journal of Gastroenterology and Hepatology. 9. 128-133 (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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