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Study of the mutations in the HCV genome and human genetic variations

Research Project

Project/Area Number 15K09004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

Ochi Hidenori  広島大学, 医歯薬保健学研究科(医), 講師 (10415119)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsHCV / ウイルス変異 / 直接作用型抗ウイルス薬 / 薬剤耐性変異 / ヒトゲノム多様性 / ゲノムワイド関連解析 / 遺伝子多型
Outline of Final Research Achievements

A system to rapidly and accurately evaluate the proportion of HCV mutant strains was developed, which enabled us to further study the efficacy of various direct acting drugs regimens and their relationships with resistant associated variants (RAVs). NS5A-Y93H substitution at baseline could be frequently found and thus regarded as naturally occurring RAV. It was associated with viral titer, the number of mutations within the NS5A-ISDR, ALT levels, and IL28B variant. Association of NS5B-C316N and core 70 amino acid substitutions with human genetic variants were examined and found that there were some associations between viral mutations and human polymorphisms. These findings may provide new insights into an understanding of viral escape from the host immune system and the viral molecular evolution as well as the virological mechanisms of HCV drug resistance.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015

All Journal Article (8 results) (of which Open Access: 4 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Emergence of drug resistance-associated variants and changes in serum lipid profiles in sofosbuvir plus ledipasvir-treated chronic hepatitis C patients2017

    • Author(s)
      Kan Hiromi、Imamura Michio、Kawakami Yoshiiku、Daijo Kana、Teraoka Yuji、Honda Fumi、Nakamura Yuki、Morio Kei、Kobayashi Tomoki、Nakahara Takashi、Nagaoki Yuko、Kawaoka Tomokazu、Tsuge Masataka、Aikata Hiroshi、Hayes Clair Nelson、Miki Daiki、Ochi Hidenori、et al
    • Journal Title

      Journal of Medical Virology

      Volume: 89 Issue: 11 Pages: 1963-1972

    • DOI

      10.1002/jmv.24885

    • Related Report
      2017 Annual Research Report
    • Open Access
  • [Journal Article] Three patients treated with sofosbuvir plus ledipasvir for recurrent hepatitis C after liver transplantation2017

    • Author(s)
      Kawaoka Tomokazu、Imamura Michio、Morio Kei、Nakamura Yuki、Tsuge Masataka、Nelson Hayes Clair、Kawakami Yoshiiku、Aikata Hiroshi、Ochi Hidenori、Ishiyama Kouhei、Ohdan Hideki、Chayama Kazuaki
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 10 Issue: 2 Pages: 179-184

    • DOI

      10.1007/s12328-017-0722-7

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Efficacy and safety of ledipasvir/sofosbuvir with ribavirin in chronic hepatitis C patients who failed daclatasvir/asunaprevir therapy: pilot study2017

    • Author(s)
      Kawakami Yoshiiku、Ochi Hidenori、Hayes Clair Nelson、Imamura Michio、Tsuge Masataka、Nakahara Takashi、Katamura Yoshio、Kohno Hiroshi、Kohno Hirotaka、Tsuji Keiji、Takaki Shintaro、Mori Nami、Honda Yohji、Arataki Keiko、Takahashi Shoichi、et al
    • Journal Title

      Journal of Gastroenterology

      Volume: 53 Issue: 4 Pages: 548-556

    • DOI

      10.1007/s00535-017-1380-8

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Real-world efficacy and safety of daclatasvir and asunaprevir therapy for hepatitis C virus-infected cirrhosis patients.2017

    • Author(s)
      Morio K, Imamura M, Kawakami Y, Morio R, Kobayashi T, Yokoyama S, Nagaoki Y, Kawaoka T, Tsuge M, Hiramatsu A, Makokha GN, Hayes CN, Aikata H, Miki D, Ochi H, Honda Y, Mori N, Takaki S, Tsuji K, Chayama K.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 32 Issue: 3 Pages: 645-650

    • DOI

      10.1111/jgh.13511

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Safety and efficacy of dual therapy with daclatasvir and asunaprevir for older patients with chronic hepatitis C.2017

    • Author(s)
      Morio R, Imamura M, Kawakami Y, Morio K, Kobayashi T, Yokoyama S, Kimura Y, Nagaoki Y, Kawaoka T, Tsuge M, Hiramatsu A, Nelson Hayes C, Aikata H, Takahashi S, Miki D, Ochi H, Mori N, Takaki S, Tsuji K, Chayama K.
    • Journal Title

      J Gastroenterol.

      Volume: 52 Issue: 4 Pages: 504-511

    • DOI

      10.1007/s00535-016-1255-4

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy and safety of daclatasvir plus asunaprevir therapy for chronic hepatitis C patients with renal dysfunction.2017

    • Author(s)
      Nakamura Y, Imamura M, Kawakami Y, Teraoka Y, Daijo K, Honda F, Morio K, Kobayashi T, Nakahara T, Nagaoki Y, Kawaoka T, Tsuge M, Hiramatsu A, Aikata H, Hayes CN, Miki D, Ochi H, Chayama K.
    • Journal Title

      J Med Virol.

      Volume: 89 Issue: 4 Pages: 665-671

    • DOI

      10.1002/jmv.24679

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protease inhibitor resistance remains even after mutant strains become undetectable using deep sequencing2016

    • Author(s)
      Kan H, Imamura M, Uchida T, Hiraga N, Hayes CN, Tsuge M, Abe H, Aikata H, Makokha GN, Chowdhury S, Miki D, Ochi H, Ishida Y, Tateno C, Chayama K.
    • Journal Title

      Journal of Infectious Disease

      Volume: 214 Issue: 11 Pages: 1687-1694

    • DOI

      10.1093/infdis/jiw437

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Rapid, Sensitive, and Accurate Evaluation of Drug Resistant Mutant (NS5A-Y93H) Strain Frequency in Genotype 1b HCV by Invader Assay2015

    • Author(s)
      Satoshi Yoshimi, Hidenori Ochi, Eisuke Murakami, Takuro Uchida, Hiromi Kan, Sakura Akamatsu, C. Nelson Hayes, Hiromi Abe, Daiki Miki, Nobuhiko Hiraga, Michio Imamura, Hiroshi Aikata, Kazuaki Chayama.
    • Journal Title

      PLOS ONE

      Volume: 10 Issue: 6 Pages: e0130022-e0130022

    • DOI

      10.1371/journal.pone.0130022

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Protease inhibitor resistance remains even after mutant strains become undetectable using ultra-deep sequencing.2016

    • Author(s)
      Kan H, Imamura M, Hiraga N, Hayes CN, Uchida T, Miyaki E, Tsuge M, Abe-Chayama H, Aikata H, Miki D, Ochi H, Ishida Y, Tateno C, Chayama K.
    • Organizer
      67th AASLD
    • Place of Presentation
      Boston MA, USA
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 代償性肝硬変患者に対するDaclatasvir/Asunaprevir併用療法の有効性および安全性の検討2016

    • Author(s)
      盛生慶, 今村道雄, 川上由育, 中村有希, 本田芙美, 小林知樹, 長沖祐子, 河岡友和, 柘植雅貴, 平松憲, 相方浩, 越智秀典, 茶山一彰,森奈美, 高木慎太郎, 辻恵二
    • Organizer
      第20回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] 腎機能障害を有するC型慢性肝炎におけるダクラタスビル・アスナプレビル療法の有効性と安全性の検討2016

    • Author(s)
      中村有希, 今村道雄, 川上由育, 盛生慶, 盛生玲央奈, 本田芙美, 小林知樹, 中原隆志, 長沖祐子, 河岡友和, 柘植雅貴, 平松憲, 相方浩, 越智秀典, 茶山一彰, 森奈美, 高木慎太郎, 辻恵二
    • Organizer
      第20回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] Rapid, sensitive, and accurate evaluation system for drug resistant strain (NS5A-Y93H) frequency in genotype 1b HCV2015

    • Author(s)
      Hidenori Ochi, Satoshi Yoshimi, Eisuke Murakami, Takuro Uchida, Hiromi Kan, Sakura Akamatsu, C. Nelson Hayes, Hiromi Abe, Daiki Miki, Nobuhiko Hiraga, Michio Imamura, Hiroshi Aikata, Kazuaki Chayama.
    • Organizer
      AASLD Liver Meeting 2015
    • Place of Presentation
      San Francisco (United States)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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