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2007 Fiscal Year Final Research Report Summary

Influence of hepatitis B virus core promoter mutations on hepatocellular carcinoma among Japanese patients

Research Project

Project/Area Number 18590741
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TANAKA Yasuhito  Nagoya City University, Graduate School of Medical Sciences, Associate Professor (90336694)

Co-Investigator(Kenkyū-buntansha) KONDA Yutaka  Aichi Cancer Center, Division of Molecular Oncology, Chief (00419897)
YOSHIZAWA Hiroshi  Hiroshima University, Graduate School of Biomedical Sciences, Professor (30109954)
MIZOKAMI Masashi  Nagoya City University, Graduate School of Medical Sciences, Professor (40166038)
Project Period (FY) 2006 – 2007
KeywordsHepatitis B virus (HBV) / HBV genotype / core promoter Mutation / Hepatocellular carcinoma / Hepatitis B Viral replication / Chimeric mice
Research Abstract

Viral differences in enhancer II/core promoter and precore regions between the subgenotypes and their association with hepatocellular carcinoma (HCC) were assessed in 3 independent studies; 1)a matched cross-sectional control study of 118 carriers with HBV/C1/Cs and 210 HBV/C2/Ce; 2) a control study among 8 IC and 8 HCC patients infected with HBV genotype C before and after seroconversion; 3)an age, sex, and HBeAg status matched cross-sectional control study between 80 Japanese patients infected with HBV/C2 with HCC and 80 without HCC. Our data indicate that T1653 and/or V1753 mutations in addition to T1762/A1764 are strongly associated with HCC in context of HBeAg status among HBV/C-carriers. HBV/C subgenotypes have specific mutation patterns, which is probably responsible for increased carcinogenesis of HBV/C2/Ce.
HBV of various genotypes may induce liver disease of distinct severity, but the underlying virological differences are not well defined. Huh7 cells were transfected with plasmids carrying 1.24-fold the HBV genome of different genotypes/subgenotypes (2 strains each for Aa/A1, Ae/A2, Ba/B2 and D; 3 each for Bj/B1 and C). uPA/SCID mice with human hepatocytes were inoculated with mouse passages of virions recovered from culture supernatants. Serum levels of HBV DNA in these mice were higher for C than Ae by 2 logs during 4-7 weeks post-inoculation. In conclusion, virological differences among HBV genotypes were demonstrated both in tissue culture and chimeric mice. These differences may influence HBV infections with distinct genotypes in clinical and epidemiological settings.

  • Research Products

    (39 results)

All 2008 2007 2006

All Journal Article (18 results) (of which Peer Reviewed: 9 results) Presentation (21 results)

  • [Journal Article] Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C,specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels2008

    • Author(s)
      Yuen MF.
    • Journal Title

      Gut. 57(1)

      Pages: 98-102

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/ C, specific mutations of enhancer II/ core promoter/precore regions and HBV DNA levels2008

    • Author(s)
      Yuen, MF
    • Journal Title

      Gut 57(1)

      Pages: 98-102

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genetic diversity of hepatitis B virus as an important factor associated with differences in clinical outcomes2007

    • Author(s)
      Tanaka Y.
    • Journal Title

      J Infect Dis. 195(1)

      Pages: 1-4

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Comparison of Complete Sequences of Hepatitis B Virus Genotype Cbetween Inactive Carriers and Hepatocellular Carcinoma Patients before and after Seroconversion2007

    • Author(s)
      Ito K.
    • Journal Title

      J astoroenterol. 42(10)

      Pages: 837-844

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Influence of hepatitis B virus X,core promote mutations on hepatocellular carcinoma among patients with subgenotype C2007

    • Author(s)
      Shinkai N.
    • Journal Title

      J CIin Microbiol. 45(10)

      Pages: 3191-3197

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Variations in the core promoter/pre-core region in HBV genotype Cin Japanese and Northern Vietnamese patients2007

    • Author(s)
      Truong BX.
    • Journal Title

      J Med Virol. 79(9)

      Pages: 1293-1304

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Clinical and Virological characteristics of hepatitis B virus subgenotypes Ba,C1 and C2 in China2007

    • Author(s)
      Wang Z.
    • Journal Title

      J CIin Microbiol. 45(5)

      Pages: 1491-1496

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Early Dynamics of Hepatitis B Virus in Chimeric Mice Carrying Human Hepatocytes Mono- or Coinfected with Genotype G2007

    • Author(s)
      Sugiyama M.
    • Journal Title

      Hepatology 45(4)

      Pages: 929-937

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Genetic diversity of hepatitis B virus as an important factor associated with differences in clinical outcomes2007

    • Author(s)
      Tanaka, Y
    • Journal Title

      J Infect Dis 195(1)

      Pages: 1-4

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Comparison of Complete Sequences of Hepatitis B Virus Genotype Cbetween Inactive Carriers and Hepatocellular Carcinoma Patients before and after Seroconversion2007

    • Author(s)
      Ito, K
    • Journal Title

      J Gastoroenterol 42(10)

      Pages: 837-844

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Influence of hepatitis B virus X, core promote mutations on hepatocellular carcinoma among patients with subgenotype C2007

    • Author(s)
      Shinkai, N
    • Journal Title

      J Clin Microbiol 45(10)

      Pages: 3191-3197

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Variations in the core promoter/pre-core region in HBV genotype C in Japanese and Northern Vietnamese patients2007

    • Author(s)
      Truong, BX
    • Journal Title

      J Med Virol 79(9)

      Pages: 1293-1304

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinical and Virological characteristics of hepatitis B virus subgenotypes Ba, C1 and C2 in China2007

    • Author(s)
      Wang, Z
    • Journal Title

      J Clin Microbiol 45(5)

      Pages: 1491-1496

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Early Dynamics of Hepatitis B Virus in Chimeric Mice Carrying Human Hepatocytes Mono- or Coinfected with Genotype G2007

    • Author(s)
      Sugiyama, M
    • Journal Title

      Hepatology 45(4)

      Pages: 929-937

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Influences of Hepatitis B Virus Genotypes on the Intra- and Extracellular Expression of Viral DNA and Antigens2006

    • Author(s)
      Sugiyama M.
    • Journal Title

      Hepatology 44(4)

      Pages: 915-924

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Specific Mutations in Enhancer II/Core Promoter of Hepatitis B Virus Subgenotypes C1/C2 Increase the Risk of Hepatocellular Carcinoma2006

    • Author(s)
      Tanaka Y.
    • Journal Title

      J Hepatol. 45(5)

      Pages: 646-653

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Influences of Hepatitis B Virus Genotypes on the Intra- and Extracellular Expression of Viral DNA and Antigens2006

    • Author(s)
      Sugiyama, M
    • Journal Title

      Hepatology 44(4)

      Pages: 915-924

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Specific Mutations in Enhancer II/Core Promoter of Hepatitis B Virus Subgenotypes C1/C2 Increase the Risk of Hepatocellular Carcinoma2006

    • Author(s)
      Tanaka, Y
    • Journal Title

      J Hepatol. 45(5)

      Pages: 646-653

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Identification of Virological Factors Differentiating Fulminant from Acute Self-Limited Hepatitis B2007

    • Author(s)
      Kusakabe, A
    • Organizer
      The 37th Annual Meeting of Japanese Society
    • Place of Presentation
      Nagasaki
    • Year and Date
      20071202-07
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Hepatitis B virus reactivation during and after chemotherapy2007

    • Author(s)
      Sugauchi, F
    • Organizer
      The 37th Annual Meeting of Japanese Society
    • Place of Presentation
      Nagasaki
    • Year and Date
      20071202-07
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Differences of early dynamics and liver damage among hepatitis B virus genotypes in uPA/SCID mice with human hepatocytes2007

    • Author(s)
      Sugiyama, M
    • Organizer
      58th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Year and Date
      20071102-1206
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] In vitro in fection of immortalized human hepatocytes by hepatitis Bvirus and its application to anti-viral treatment2007

    • Author(s)
      Tanaka Y.
    • Organizer
      58th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Year and Date
      20071102-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Differences of early dynamics and liver damage among hepatitis Bvirus genotypes in uPA/SLID mice with human hepatocytes2007

    • Author(s)
      Sugiyama M.
    • Organizer
      58th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Year and Date
      20071102-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] In vitro infection of immortalized human hepatocytes by hepatitis B virus and its application to and-viral treatment2007

    • Author(s)
      Tanaka, Y
    • Organizer
      58th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Year and Date
      20071102-06
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] エンテカビル治療効果及び耐駐変異に関する検討2007

    • Author(s)
      田中 靖人
    • Organizer
      第11回日本肝臓学会大会
    • Place of Presentation
      神戸
    • Year and Date
      20071018-19
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Efficiency and resistance of entecavir therapy in Japanese patients2007

    • Author(s)
      Tanaka, Y
    • Organizer
      The 11th Annual Meeting of Japan Society of Hepatology
    • Place of Presentation
      Kobe
    • Year and Date
      20071018-19
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Application of chimeric mice with human hepatocytes in hepatitis B virus research2007

    • Author(s)
      Tanaka Y.
    • Organizer
      APDW2007 Asian Pacific Digestive Week 2007
    • Place of Presentation
      Kobe
    • Year and Date
      20071015-18
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] A novel three-dimensional long-term culture system of human hepatocytes for hepatitis B virus infection2007

    • Author(s)
      Tanaka Y.
    • Organizer
      2007 International HBV meeting:The Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Italy
    • Year and Date
      20070916-20
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] A novel three-dimensional long-term culture system of human hepatocytes for hepatitis B virus infection2007

    • Author(s)
      Tanaka, Y
    • Organizer
      2007 International HBV meeting: The Molecular Biology of Hepatitis B B Viruses
    • Place of Presentation
      Italy
    • Year and Date
      20070916-20
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 肝炎ウイルス研究の進歩。ヒト肝細胞置換キメラマウスでのHBV遺伝子型による複製効率の違い2007

    • Author(s)
      杉山 真也
    • Organizer
      第43回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      20070531-0601
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Difference of viral replication of hepatitis B virus genotypes using chimeric mice2007

    • Author(s)
      Sugiyama, M
    • Organizer
      The 43rd Annual Meeting of Japan Society of Japan Society of Hepatology
    • Place of Presentation
      Tokyo
    • Year and Date
      20070531-0601
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] B型肝炎急性増悪に対する方策.早期治療介入を目指したB型劇症肝炎予測ウイルス因子の検討2007

    • Author(s)
      日下 部篤宣
    • Organizer
      第37回日本肝臓学会西部会
    • Place of Presentation
      長崎
    • Year and Date
      2007-12-07
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] B型肝炎急性増悪に対する方策.免疫抑制・化学療法後に発生するB型肝炎ウイルス再活性化に対する方策2007

    • Author(s)
      菅内 文中
    • Organizer
      第37回日本肝臓学会西部会
    • Place of Presentation
      長崎
    • Year and Date
      2007-12-07
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Development of novel tree-dementional long-term culture system of human hepatocytes for hepatitis B virus infection2006

    • Author(s)
      Tanaka Y.
    • Organizer
      57th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Year and Date
      20061027-31
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Replication of hepatitis B virus genotype G requiresco-infection with other genotypes in uPA/SCID mice carrying human hepatocytes2006

    • Author(s)
      Sakamoto T.
    • Organizer
      57th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Year and Date
      20061027-31
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Influence of hepatitis B virus genotypes on liver injury in vitro and in vivo2006

    • Author(s)
      Sugiyama M.
    • Organizer
      57th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Year and Date
      20061027-31
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Replication of hepatitis B virus genotype G requires co-infection with other genotypes in uPA/SCID mice carrying human hepatocytes2006

    • Author(s)
      Sakamoto, T
    • Organizer
      57th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Year and Date
      20061027-31
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 肝炎ウイルスによる肝障害機序と肝発癌機序の解明HBV core promoter変異と肝発癌機序の解明2006

    • Author(s)
      伊藤 清顕
    • Organizer
      第92回日本消化器病学会総会
    • Place of Presentation
      小倉
    • Year and Date
      20060420-21
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Core promoter mutations increase the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Genotype C2006

    • Author(s)
      Ito, K
    • Organizer
      The 92nd Annual Meeting of the Japanese Society of Gastroenterology
    • Place of Presentation
      Kokura
    • Year and Date
      20060420-21
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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