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Mechanisms for hepatitis B virus replication and mutagenesis : investigations using virus-expressing mouse system.

Research Project

Project/Area Number 20590776
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

OHKAWA Kazuyoshi  Osaka University, 肝胆膵内科, 副部長 (80432540)

Co-Investigator(Kenkyū-buntansha) TATSUMI Tomohide  大阪大学, 大学院・医学系研究科・消化器内科学, 助教 (20397699)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肝臓学 / B型肝炎 / B型肝炎ウイルス複製 / B型肝炎ウイルス変異 / 無症候性HBVキャリア / 活動性B型肝炎発症 / HBV増殖活性 / インターフェロン-γ / 核酸アナログ / 薬剤耐性変異ウイルス / B型劇症肝疾患
Research Abstract

We studied hepatitis B virus (HBV) replication and mutagenesis using in vitro and in vivo HBV-expressing systems. The findings showed that 1) HBV preS/S protein may not affect HBV replication in a single HBV-infected cell, that 2) interferon-γ may not play a role on the initial eradication of HBV, that 3) the novel type of HBV mutation associated with fulminant hepatic failure was identified, that 4) HBV mutations occurring from immunotolerant phase to immunoactive phase may reduce HBV replication, that 5) precore and preS2 mutations may support replication of lamivudine-resistant HBV, that 6) V1753 and C2189 mutations may result in the improved antiviral efficacy against adefovir, and that 7) the novel HBV mutation that confer resistance to multiple nucleos(t)ide analogs was identified.

Report

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

    (29 results)

All 2010 2009 2008

All Journal Article (20 results) (of which Peer Reviewed: 9 results) Presentation (9 results)

  • [Journal Article] Prior splenic irradiation reduces hematologic adverse events during chemotherapy in pancreatic tail cancer : a report of a patient with liver cirrhosis.2010

    • Author(s)
      Ohkawa K, et al.
    • Journal Title

      Clin J Gasroenterol 3

      Pages: 337-42

    • Related Report
      2010 Final Research Report
  • [Journal Article] Improved diagnosis of well-differentiated hepatocellular carcinoma with Gd-EOB-DTPA-enhanced MRI and Sonazoid contrast-enhanced ultrasonography.2010

    • Author(s)
      Kawada N, Ohkawa K, et al.
    • Journal Title

      Hepatol Res 40

      Pages: 930-6

    • Related Report
      2010 Final Research Report
  • [Journal Article] Alterations in hepatitis B virus nucleotide sequences in a chronic virus carrier from immunotolerant to immunoactive phase.2010

    • Author(s)
      Ohkawa K, et al.
    • Journal Title

      Biochem Biophys Res Commun 394

      Pages: 574-80

    • Related Report
      2010 Final Research Report
  • [Journal Article] Fatal exacerbation of type B chronic hepatitis triggered by changes in relaxed circular viral DNA synthesis and virion secretion.2010

    • Author(s)
      Ohkawa K, et al.
    • Journal Title

      Biochem Biophys Res Commun 394

      Pages: 87-93

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Journal Article] Alterations in hepatitis B virus nucleotide sequences in a chronic virus carrier from immunotolerant to immunoactive phase.2010

    • Author(s)
      Ohkawa K, et al.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 394 Pages: 574-80

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improved diagnosis of well-differentiated hepatocellular carcinoma with Gd-EOB-DTPA-enhanced MRI and Sonazoid contrast-enhanced ultrasonography.2010

    • Author(s)
      Kawada N, Ohkawa K, et al.
    • Journal Title

      Hepatol Res

      Volume: 40 Pages: 930-6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prior splenic irradiation reduces hematologic adverse events during chemotherapy in pancreatic tail cancer : a report of a patient with liver cirrhosis.2010

    • Author(s)
      Ohkawa K, et al.
    • Journal Title

      Clin J Gasroenterol

      Volume: 3 Pages: 337-42

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two kinds of drug-resistant hepatitis B viral strains emerging alternately and their susceptibility to combination therapy with entecavir and adefovir.2009

    • Author(s)
      Kurashige N, Ohkawa K, et al.
    • Journal Title

      Antivir Ther 14

      Pages: 873-7

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Journal Article] Lamivudine-to-entecavir switching treatment in type B chronic hepatitis patients without evidence of lamivudine resistance.2009

    • Author(s)
      Kurashige N, Ohkawa K, et al.
    • Journal Title

      J Gastroenterol 44

      Pages: 864-70

    • Related Report
      2010 Final Research Report
  • [Journal Article] Factors contributing to antiviral effect of adefovir dipivoxil therapy added to ongoing lamivudine treatment in patients with lamivudine-resistant chronic hepatitis2009

    • Author(s)
      Kurashige N, Hiramatsu N, Ohkawa K, et al.
    • Journal Title

      B.J Gastroenterol 44

      Pages: 601-7

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mutations associated with the therapeutic efficacy of adefovir dipivoxil added to lamivudine in patients resistant to lamivudine with type B chronic hepatitis.2009

    • Author(s)
      Ohkawa K, et al.
    • Journal Title

      J Med Virol 81

      Pages: 798-806

    • Related Report
      2010 Final Research Report
  • [Journal Article] Factors contributing to antiviral effect of adefovir dipivoxil therapy added to ongoing lamivudine treatment in patients with lamivudine-resistant chronic hepatitis B.2009

    • Author(s)
      Kurashige N, Hiramatsu N, Ohkawa K, et al.
    • Journal Title

      Journal of Gastroenterology 44

      Pages: 601-7

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lamivudine-to-entecavir switching treatment in type B chronic hepatitis patients without evidence of lamivudine resistance.2009

    • Author(s)
      Kurashige N, Ohkawa K, et al.
    • Journal Title

      Journal of Gastroenterology 44

      Pages: 864-70

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations associated with the therapeutic efficacy of adefovir dipivoxiladded to lamivudine in patients with type B chronic hepatitis.2009

    • Author(s)
      Ohkawa K, et al.
    • Journal Title

      Journal of Medical Virology (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Supportive role played by precore and preS2 genomic changes in the establishment of lamivudine-resistant hepatitis B virus.2008

    • Author(s)
      Ohkawa K, et al.
    • Journal Title

      J Infect Dis 198

      Pages: 1150-8

    • Related Report
      2010 Final Research Report
  • [Journal Article] Early emergence of entecavir-resistant hepatitis B virus in a patient with hepatitis B virus/human immunodeficiency virus coinfection.2008

    • Author(s)
      Kanada A, Takehara T, Ohkawa K, et al.
    • Journal Title

      Hepatol Res 38

      Pages: 622-8

    • Related Report
      2010 Final Research Report
  • [Journal Article] Initial viral response is the most powerful predictor of the emergence of YMDD mutant virus in chronic hepatitis B patients treated with lamivudine.2008

    • Author(s)
      Kurashige N, Hiramatsu N, Ohkawa K, et al.
    • Journal Title

      Hepatol Res 38

      Pages: 450-6

    • Related Report
      2010 Final Research Report
  • [Journal Article] Early emergence of entecavir-resistant hepatitis B virus in a patientwith hepatitis B virus/human immunodeficiency virus coinfection.2008

    • Author(s)
      Kanada A, Takehara T, Ohkawa K, et al.
    • Journal Title

      Hepatology Research 38

      Pages: 622-8

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Initial viral response is the most powerful predictor of the emergenceof YMDD mutant virus in chronic hepatitis B patients treated withlamivudine.2008

    • Author(s)
      Kurashige N, Hiramatsu N, Ohkawa K, et al.
    • Journal Title

      Hepatology Research 38

      Pages: 450-6

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Supportive role played by precore and preS2 genomic changes in the establishment of lamivudine-resistant hepatitis B virus.2008

    • Author(s)
      Ohkawa K, et al.
    • Journal Title

      The Journal of Infectious Diseases 198

      Pages: 1150-8

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 長期経過観察を経て肝炎を発症したHBe抗原陽性無症候性HBVキャリアの1症例におけるHBV全塩基配列の経時的変化とその病態的意義についての検討2010

    • Author(s)
      大川和良, ら
    • Organizer
      第46回日本肝臓学会総会
    • Place of Presentation
      山形
    • Year and Date
      2010-05-27
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] エンテカビル治療を施行したB型慢性肝疾患症例における薬剤耐性についての検討2009

    • Author(s)
      大川和良, ら
    • Organizer
      第13回日本肝臓学会大会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-15
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 9年間の経過観察を経て肝炎を発症したHBe抗原陽性無症候性HBVキャリアの1症例における各種HBVマーカーならびにHBV全塩基配列の経時的検討2009

    • Author(s)
      大川和良, ら
    • Organizer
      第45回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2009-06-05
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] ラミブジンからエンテカビルへの切替症例におけるラミブジン非耐性B型慢性肝疾患の治療成績-OLF多施設共同研究2009

    • Author(s)
      倉繁奈緒、平松直樹、大川和良, ら
    • Organizer
      第45回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2009-06-04
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Supportive activity of precore and preS2 viral genomic changes against replication of lamivudine-resistant hepatitis B virus.2008

    • Author(s)
      大川和良, et al.
    • Organizer
      The 59th Annual Meeting of the American Association for the Study of Liver Diseases.
    • Place of Presentation
      San Francisco
    • Year and Date
      2008-11-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Supportive activity of precore and preS2 viral genomic changes against replication of lamivudine-resistant hepatitis B virus.2008

    • Author(s)
      Ohkawa K, et al.
    • Organizer
      The 59th Annual Meeting of the AmericanAssociation for the Study of Liver Diseases
    • Place of Presentation
      San Francisco
    • Year and Date
      2008-11-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] OLF参加施設におけるB型慢性肝疾患に対するエンテカビルの治療成績2008

    • Author(s)
      倉繁奈緒、平松直樹、大川和良, ら
    • Organizer
      第12回日本肝臓学会大会
    • Place of Presentation
      東京
    • Year and Date
      2008-10-01
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] OLF参加施設におけるB型慢性肝疾患に対する核酸アナログ療法の治療成績2008

    • Author(s)
      倉繁奈緒、平松直樹、大川和良, ら
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山
    • Year and Date
      2008-06-06
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] ラミブジン耐性B型肝炎ウイルス成立機転に対するprecoreならびにpreS2変異の補助的役割2008

    • Author(s)
      大川和良, ら
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山
    • Year and Date
      2008-06-05
    • Related Report
      2010 Final Research Report 2008 Annual Research Report

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

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