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Development of the treatment strategy for HCV-related diseases using ultra-deep sequencing technology.

Research Project

Project/Area Number 24590965
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionUniversity of Yamanashi

Principal Investigator

MAEKAWA Shinya  山梨大学, 総合研究部, 講師 (70397298)

Co-Investigator(Renkei-kenkyūsha) ENOMOTO Nobuyuki  山梨大学, 総合研究部, 教授 (20251530)
MIURA Mika  山梨大学, 総合研究部, 助教 (00436875)
KOMATSU Nobutoshi  山梨大学, 総合研究部, 助教 (50568003)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsHCV / Ultra-deep sequence / DAA / 耐性変異 / Quasispecies / 系統樹 / Ultra-deep sequencing / 3者併用療法
Outline of Final Research Achievements

It has been hard to predict the treatment response of HCV-infected patients to the most advanced DAA-included therapy. Using ultra-deep sequencing technology coupled with phylogenetic analysis, this study was conducted to disclose the role of viral quasispecies in determining the treatment response to DAA-included anti-HCV therapy. As a result, it was disclosed that viral quasispecies changed dynamically and certain viral isolates were selected with the introduction of DAA-based therapy. The result of the study provides better understanding of the mechanism in the appearance of DAA resistance.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (19 results)

All 2015 2014 2013 2012

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 3 results) Presentation (4 results) Book (2 results)

  • [Journal Article] Deep sequencing and phylogenetic analysis of variants resistant to interferon-based protease inhibitor therapy in chronic hepatitis induced by genotype 1b hepatitis C virus.2015

    • Author(s)
      Sato M, Maekawa S, Komatsu N, Tatsumi A, Miura M, Muraoka M, Suzuki Y, Amemiya F, Takano S, Fukasawa M, Nakayama Y, Yamaguchi T, Uetake T, Inoue T, Sato T, Sakamoto M, Yamashita A, Moriishi K, Enomoto N.
    • Journal Title

      J Virol

      Volume: 89(11) Issue: 11 Pages: 6105-16

    • DOI

      10.1128/jvi.03127-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Naturally occurring, resistance-associated hepatitis C virus NS5A variants are linked to IL28B genotype and are sensitive to interferon-based therapy.2015

    • Author(s)
      Itakura J, Kurosaki M, Takada H, Nakakuki N, Matsuda S, Gondou K, Asano Y, Hattori N, Itakura Y, Tamaki N, Yasui Y, Suzuki S, Hosokawa T, Tsuchiya K, Nakanishi H, Takahashi Y, Maekawa S, Enomoto N, Izumi N.
    • Journal Title

      Hepatol Res.

      Volume: [Epub ahead of print] Issue: 10

    • DOI

      10.1111/hepr.12474

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C.2015

    • Author(s)
      Iio E, Matsuura K, Nishida N, Maekawa S, Enomoto N, Nakagawa M, Sakamoto N, Yatsuhashi H et al.
    • Journal Title

      Hum Genet

      Volume: 134 Issue: 3 Pages: 279-289

    • DOI

      10.1007/s00439-014-1520-7

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hallmarks of hepatitis C virus in equine hepacivirus.2015

    • Author(s)
      Tanaka T, Kasai H, Yamashita A, Okuyama-Dobashi K, Yasumoto J, Maekawa S, Enomoto N, Okamoto T, Matsuura Y, Morimatsu M, Manabe N, Ochiai K, Yamashita K, Moriishi K.
    • Journal Title

      J Virol.

      Volume: 88(22) Issue: 22 Pages: 13352-66

    • DOI

      10.1128/jvi.02280-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatocellular carcinoma risk assessment using gadoxetic acid-enhanced hepatocyte phase magnetic resonance imaging.2015

    • Author(s)
      Komatsu N, Motosugi U, Maekawa S, Shindo K, Sakamoto M, Sato M, Tatsumi A, Miura M, Amemiya F, Nakayama Y, Inoue T, Fukasawa M, Uetake T, Ohtaka M, Sato T, Asahina Y, Kurosaki M, Izumi N, Ichikawa T, Araki T, Enomoto N.
    • Journal Title

      Hepatol Res

      Volume: - Issue: 13 Pages: 1339-1346

    • DOI

      10.1111/hepr.12309

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Deep sequencing analysis of variants resistant to the non-structural 5A inhibitor daclatasvir in patients with genotype 1b hepatitis C virus infection.2014

    • Author(s)
      Miura M, Maekawa S, Sato M, Komatsu N, Tatsumi A, Takano S, Amemiya F, Nakayama Y, Inoue T, Sakamoto M, Enomoto N.
    • Journal Title

      Hepatol Res.

      Volume: Feb 25 Issue: 14

    • DOI

      10.1111/hepr.12316

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Once-daily simeprevir in combination with pegylated-interferon and ribavirin: a new horizon in the era of direct-acting antiviral agent therapy for chronic hepatitis C.2014

    • Author(s)
      Maekawa S, Enomoto N
    • Journal Title

      J Gastroenterol.

      Volume: 49(1) Issue: 12 Pages: 163-164

    • DOI

      10.1371/journal.pone.0082299

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effects of caffeic Acid phenethyl ester derivatives on replication of hepatitis C virus.2013

    • Author(s)
      Shen H, Yamashita A, Nakakoshi M, Yokoe H, Sudo M, Kasai H, Tanaka T, Fujimoto Y, Ikeda M, Kato N, Sakamoto N, Shindo H, Maekawa S, Enomoto N, Tsubuki M, Moriishi K.
    • Journal Title

      PLoS One.

      Volume: 17 Issue: 1 Pages: 163-164

    • DOI

      10.1007/s00535-013-0926-7

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Deep-sequencing analysis of the association between the quasispecies nature of the hepatitis C virus core region and disease progression.2013

    • Author(s)
      Miura M, Maekawa S, Takano S, Komatsu N, Tatsumi A, Asakawa Y, Shindo K, Amemiya F, Nakayama Y, Inoue T, Sakamoto M, Yamashita A, Moriishi K, Enomoto N.
    • Journal Title

      J Virol.

      Volume: 87(23) Issue: 23 Pages: 12541-12551

    • DOI

      10.1128/jvi.00826-13

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] IL-28B (IFN-λ3) and IFN-α synergistically inhibit HCV replication.2013

    • Author(s)
      Shindo H
    • Journal Title

      J Viral Hepat.

      Volume: 20 Issue: 4 Pages: 281-289

    • DOI

      10.1111/j.1365-2893.2012.01649.x

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum RANTES level influences the response to pegylated interferon and ribavirin therapy in chronic hepatitis C.2013

    • Author(s)
      Komase K, Maekawa S, Miura M, Sueki R, Kadokura M, Shindo H, Shindo K, Amemiya F, Nakayama Y, Inoue T, Sakamoto M, Yamashita A, Moriishi K, Enomoto N
    • Journal Title

      Hepatol Res.

      Volume: 43(8) Issue: 8 Pages: 865-875

    • DOI

      10.1111/hepr.12032

    • NAID

      10031194591

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Correlation between pretreatment viral sequences and the emergence of lamivudine resistance in hepatitis B virus infection.2012

    • Author(s)
      Sueki R
    • Journal Title

      J Med Virol.

      Volume: 84(9) Issue: 9 Pages: 1360-1368

    • DOI

      10.1002/jmv.23314

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comprehensive analysis for viral elements and interleukin-28B polymorphisms in response to pegylated interferon plus ribavirin therapy in hepatitis C virus 1B infection.2012

    • Author(s)
      Maekawa S
    • Journal Title

      Hepatology.

      Volume: 56(5) Issue: 5 Pages: 1611-1621

    • DOI

      10.1002/hep.25826

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Deep Sequencing Analysis Of Variants Resistant To Ns5a Inhibitors In Patients With Genotype 1b Hepatitis C Virus Infection.2014

    • Author(s)
      S. Maekawa, M. Miura, M. Sato, N. Komatsu, Y. Nakayama, T. Inoue, M. Sakamoto, N.
    • Organizer
      AASLD Liver Meeting
    • Place of Presentation
      ボストン(米国、マサチューセッツ)
    • Year and Date
      2014-11-08 – 2014-11-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Deep-sequenceを用いたnaturally-occurring DAA resistant HCVの検討2014

    • Author(s)
      前川伸哉、三浦美香、辰巳明久、小松信俊、佐藤光明、鈴木雄一朗、雨宮史武、中山康弘、井上泰輔、坂本穣、榎本信幸
    • Organizer
      第50回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ(東京都千代田区)
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 次世代sequencerによるtelaprevir耐性変異の解析2014

    • Author(s)
      佐藤光明、三浦美香、前川伸哉、小松信俊、辰巳明久、中山康弘、井上泰輔、坂本穣、榎本信幸
    • Organizer
      第50回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ(東京都千代田区
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 発癌リスクと治療反応性、薬剤耐性変異を考慮した難治性C型肝炎治療2014

    • Author(s)
      坂本穣、前川伸哉、榎本信幸
    • Organizer
      第50回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ(東京都千代田区
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Book] HEPATOLOGY PRACTICE C型肝炎の診療を極める2014

    • Author(s)
      前川伸哉、榎本信幸
    • Publisher
      文光堂
    • Related Report
      2014 Annual Research Report
  • [Book] 臨床消化器内科 6月増刊号 C型肝炎のすべて2014

    • Author(s)
      前川伸哉、榎本信幸
    • Publisher
      診断と治療社
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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