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Mechanism of drug resistance among HBV genotypes

Research Project

Project/Area Number 20390213
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNagoya City University

Principal Investigator

MIZOKAMI Masashi  Nagoya City University, 大学院・医学研究科, 客員教授 (40166038)

Co-Investigator(Kenkyū-buntansha) TANAKA Yasuhito  名古屋市立大学, 大学院・医学研究科, 教授 (90336694)
SUGAUCHI Fuminaka  名古屋市立大学, 大学院・医学研究科, 研究員 (20405161)
FUAT Kurbanov  名古屋市立大学, 大学院・医学研究科, 特任助教 (10444978)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
KeywordsB型肝炎ウイルス / エンテカビル / ラミブジン / 薬剤耐性 / キメラマウス / HBV / HBV遺伝子型
Research Abstract

1. Randomized controlled trial evidenced that switching treatment to ETV was recommended during at least 2 years' follow-up period in patients treated with LAM for more than 3 years maintaining HBV DNA less than 2.6 log copies/m. 2. Using chimeric mice model, we found new small compounds to inhibit ETV resistant. 3. We found that the low binding affinity for ETV to the DNA binding domains, involving conformationalchange of the binding pocket of HBV RT by the ETVr substitutions, could induce BT. ETV should be considered as a first-line option for nucleoside-naive patients ; however, it is not an optimal therapy for patients with LVDr.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (41 results)

All 2011 2010 2009 2008

All Journal Article (21 results) (of which Peer Reviewed: 19 results) Presentation (20 results)

  • [Journal Article] Evolution of hepatitis B genotype C viral quasi-species during hepatitis B e antigen seroconversion.2011

    • Author(s)
      Wu S, Tanaka Y, Mizokami M. et al.
    • Journal Title

      J Hepatol 54(1)

      Pages: 19-25

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A population-based cohort study for the risk factors of HCC among hepatitis B virus mono-infected subjects in Japan.2011

    • Author(s)
      Kusakabe A, Tanaka Y, Mizokami M. et al.
    • Journal Title

      J Gastroenterol 46(1)

      Pages: 117-124

    • NAID

      10029026880

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transmissibility of Hepatitis B Virus (HBV) Infection through Blood Transfusion from Blood Donors with Occult HBV Infection.2011

    • Author(s)
      Yuen MF, Tanaka Y, Sugauchi F, Mizokami M. et al.
    • Journal Title

      Clin Infect Dis 52(5)

      Pages: 624-632

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Virological and clinical characteristics on reactivation of occult hepatitis B in patients with hematological malignancy.2011

    • Author(s)
      Sugauchi F, Tanaka Y, Mizokami M. et al.
    • Journal Title

      J Med Virol 83(3)

      Pages: 412-418

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reactivation of hepatitis B virus following rituximab-plus-steroid combination chemotherapy.2011

    • Author(s)
      Kusumoto S, Tanaka Y, Mizokami M.
    • Journal Title

      J Gastroenterol.

      Volume: 46(1) Pages: 9-16

    • NAID

      10029026408

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A population-based cohort study for the risk factors of HCC among hepatitis B virus mono-infected subjects in Japan.2011

    • Author(s)
      Kusakabe A, Tanaka Y, Mizokami M.
    • Journal Title

      J Gastroenterol.

      Volume: 46(1) Pages: 117-124

    • NAID

      10029026880

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transmissibility of Hepatitis B Virus (HBV) Infection through Blood Transfusion from Blood Donors with Occult HBV Infection.2011

    • Author(s)
      Yuen MF, Tanaka Y, Sugauchi F, Mizokami M.
    • Journal Title

      Clin Infect Dis.

      Volume: 52(5) Pages: 624-632

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Virological and clinical characteristics on reactivation of occult hepatitis B in patients with hematological malignancy.2011

    • Author(s)
      Sugauchi F, Tanaka Y, Mizokami M.
    • Journal Title

      J Med Virol.

      Volume: 83(3) Pages: 412-418

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recommendation of Lamivudine-to-Entecavir switching treatment in chronic hepatitis B responders : Randomized controlled trial2011

    • Author(s)
      Matsuura K, Tanaka Y, Mizokami M.
    • Journal Title

      Hepatol Res.

      Volume: (印刷中)

    • NAID

      10031144118

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Occult hepatitis B in the genotype H-infected Nahuas and Huichol native Mexican population.2010

    • Author(s)
      Roman S, Tanaka Y, Mizokami M. et al.
    • Journal Title

      J Med Virol 82(9)

      Pages: 1527-1536

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Occult hepatitis B in the genotype H-infected Nahuas and Huichol native Mexican population.2010

    • Author(s)
      Roman S, Tanaka Y, Mizokami M.
    • Journal Title

      J Med Virol.

      Volume: 82(9) Pages: 1527-1536

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evolution of hepatitis B genotype C viral quasi-species during hepatitis B e antigen seroconversion.2010

    • Author(s)
      Wu S, Tanaka Y, Mizokami M.
    • Journal Title

      J Hepatol.

      Volume: 54(1) Pages: 19-25

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of entecavir resistance of hepatitis B virus with viral breakthrough as determined by long-term clinical assessment and molecular docking simulation2010

    • Author(s)
      Mukaide M
    • Journal Title

      Antimicrob Agents Chemother. 54(2)

      Pages: 882-889

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distribution of Hepatitis B Virus Genotypes among Patients with Chronic Infection in Japan Shifting toward an Increase of Genotype A.2009

    • Author(s)
      Matsuura K, Tanaka Y, Mizokami M. et al.
    • Journal Title

      J Clin Microbiol 47(5)

      Pages: 1476-1483

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 【性感染症への対応と治療】肝炎ウイルス2009

    • Author(s)
      菅内文中
    • Journal Title

      臨床婦人科産科 63(2)

      Pages: 157-161

    • Related Report
      2009 Annual Research Report
  • [Journal Article] B型肝炎の治療最前線 B型慢性肝炎に対するエンテカビル治療2009

    • Author(s)
      田中靖人
    • Journal Title

      臨床消化器内科 24

      Pages: 691-699

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 「イムニスHBVゲノタイプEIA」の基礎的・臨床的検討2009

    • Author(s)
      田中靖人
    • Journal Title

      臨床病理 57(1)

      Pages: 42-47

    • NAID

      10025224164

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A2009

    • Author(s)
      Matsuura K
    • Journal Title

      J Clin Microbiol. 47

      Pages: 1476-1483

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Case-control study for the identification of virological factors associated with fulminant hepatitis B2009

    • Author(s)
      Kusakabe A
    • Journal Title

      Hepatol Res. 24

      Pages: 691-699

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characteristics of hepatitis B virus genotype G coinfected with genotype H in Chimeric Mice Carrying Human Hepatocytes.2008

    • Author(s)
      Tanaka Y, Mizokami M. et al.
    • Journal Title

      Virology 376(2)

      Pages: 408-415

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characteristics of hepatitis B virus genotype G coinfected with genotype H in Chimeric Mice Carrying Human Hepatocytes2008

    • Author(s)
      Tanaka Yasuhito
    • Journal Title

      Virology 376(2)

      Pages: 408-415

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] IN VIVO MODEL USING UPA/SCID MICE WITH HUMAN HEPATOCYTES TO STUDY CROSS-GENOTYPE PROTECTIONS OF HBV AND A ROLE OF HBS ANTIGEN MUTATION IN IMMUNITY ESCAPE.2010

    • Author(s)
      菅内文中
    • Organizer
      The 61^<st> annual meeting of the AASLD
    • Place of Presentation
      The Hynes Convention Center (Boston USA)
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] A POPULATION-BASED COHORT STUDY FOR THE RISK FACTORS OF HCC AMONG HEPATITIS B VIRUS MONOINFECTED SUBJECT IN JAPAN.2010

    • Author(s)
      Kusakabe A. Mizokami M.
    • Place of Presentation
      The Hynes Convention Center (Boston USA)
    • Related Report
      2010 Final Research Report
  • [Presentation] ラミブジン投与例におけるエンテカビル切り替え無作為割り付け試験2010

    • Author(s)
      松浦健太郎, 溝上雅史
    • Organizer
      第46回日本肝臓学会総
    • Place of Presentation
      ホテルメトロポリタン山形(山形市)
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト肝細胞キメラマウスにおけるB型肝炎ウイルス感染防御の試み2010

    • Author(s)
      菅内文中、田中靖人、溝上雅史
    • Organizer
      第46回日本肝臓学会総
    • Place of Presentation
      ホテルメトロポリタン山形 (山形市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒト肝細胞置換キメラマウスでのHBV感染による酸化傷害と線維化2010

    • Author(s)
      杉山真也、田中靖人、溝上雅史
    • Organizer
      第46回日本肝臓学会総
    • Place of Presentation
      ホテルメトロポリタン山形 (山形市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] ラミブジン投与例におけるエンテカビル切り替え無作為割り付け試験2010

    • Author(s)
      松浦健太郎、田中靖人、溝上雅史
    • Organizer
      第46回日本肝臓学会総
    • Place of Presentation
      ホテルメトロポリタン山形 (山形市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] A POPULATION-BASEDM COHORT STUDY FOR THE RISK FACTORS OF HCC AMONG HEPATITIS B VIRUS MONOINFECTED SUBJECT IN JAPAN.2010

    • Author(s)
      Kusakabe A, Tanaka Y, Mizokami M.
    • Organizer
      The 61^<st> annual meeting of the AASLD
    • Place of Presentation
      The Hynes Convention Center (Boston USA)
    • Related Report
      2010 Annual Research Report
  • [Presentation] B型慢性肝炎難治例への対策B型肝炎に対するAdefovir、Entecavirの治療成績と多剤耐性HBV 変異株に対するTenofovir の有効性2009

    • Author(s)
      菅内文中
    • Organizer
      第13回日本肝臓学会大会
    • Place of Presentation
      京都国際会館(京都市)
    • Related Report
      2010 Final Research Report
  • [Presentation] コンセンサスミーティング:HBV遺伝子型と病態・予後2009

    • Author(s)
      田中靖人
    • Organizer
      第45回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Related Report
      2009 Annual Research Report
  • [Presentation] HBV genotype A, B, C, DにおけるHBs抗原定量の臨床的意義2009

    • Author(s)
      木村達治
    • Organizer
      第45回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Related Report
      2009 Annual Research Report
  • [Presentation] B型慢性肝炎難治例への対策 B型肝炎に対する Adefovir、 Entecavir の治療成績と多剤耐性HBV変異株に対する Tenofovir の有効性2009

    • Author(s)
      菅内文中
    • Organizer
      第13回日本肝臓学会大会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] B型肝炎に対する Entecavir の治療成績と各種血清マーカーの推移2009

    • Author(s)
      松浦健太郎
    • Organizer
      第38回日本肝臓学会西部会
    • Place of Presentation
      米子
    • Related Report
      2009 Annual Research Report
  • [Presentation] Clinical significance of a novel high-sensitivity hepatitis B surface antigen immunoassay in patients with hepatitis B virus infection2009

    • Author(s)
      菅内文中
    • Organizer
      60th American Association for the Study of Liver Disease(AASLD)
    • Place of Presentation
      Boston MA, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Identification of genetic variants associated with chronic hepatitis B or C in a genome-wide association2009

    • Author(s)
      松浦健太郎
    • Organizer
      The 8^<th> JSH Single Topic Conference
    • Place of Presentation
      Tokyo
    • Related Report
      2009 Annual Research Report
  • [Presentation] A genome-wide association study identifies genetic variants in the HLA-DP associated with chronic hepatitis B2009

    • Author(s)
      松浦健太郎
    • Organizer
      60th American Association for the Study of Liver Disease(AASLD)
    • Place of Presentation
      Boston MA, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Three-year assessment of entecavir resistance in chronic hepatitis B patients and the mechanism of viral breakthrough by the resistance substitutions.2008

    • Author(s)
      Tanaka Y.
    • Organizer
      The 59st Annual Meeting of the American Association for the Study of Liver Diseases.
    • Place of Presentation
      Moscone West Convention Center (San Francisco USA)
    • Year and Date
      2008-11-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Three-year assessment of entecavir resistance in chronic hepatitis B patients and the mechanism of viral breakthrough by the resistance substitutions2008

    • Author(s)
      Tanaka Yasuhito
    • Organizer
      59th Annual Meeting of the American Associa tion for the study of Liver Diseases
    • Place of Presentation
      San Francisco
    • Year and Date
      2008-11-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] Early Detection of Nucleotide Analogue-Resistant Mutations of Hepatitis B Virus by Novel Sensitive Methods for Prediction of Viral Breakthrough2008

    • Author(s)
      Mukaide Motokazu
    • Organizer
      59th Annual Meeting of the American Associa tion for the study of Liver Diseases
    • Place of Presentation
      San Francisco
    • Year and Date
      2008-11-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] B型肝炎ウイルスの治療. B型慢性肝炎に対するエンテカビル長期投与の有用性2008

    • Author(s)
      田中 靖人
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      愛媛
    • Year and Date
      2008-06-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] エンテカビル長期投与による治療効果及び耐性変異出現パターン2008

    • Author(s)
      田中 靖人
    • Organizer
      第94回日本消化器病学会総
    • Place of Presentation
      福岡
    • Year and Date
      2008-05-08
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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