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Diversity of viral genome mutations during clinical feature of hepatitis B virus infection

Research Project

Project/Area Number 16K09379
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Watanabe Tsunamasa  聖マリアンナ医科大学, 医学部, 講師 (20338528)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsB型肝炎ウイルス / ウイルス遺伝子変異 / 急性肝炎 / 肝細胞癌 / 次世代シークエンス解析 / ウイルス遺伝子多型 / APOBEC / 肝臓学
Outline of Final Research Achievements

Nucleot(s)ide analogues therapy cannot completely eliminate and inhibit the development of hepatocellular carcinoma (HCC). We investigated diversity of viral genome mutations during clinical feature of hepatitis B virus infection. A total of 20 acute hepatitis B (AH-B) cases were collected. For applying next-generation sequencing platform, we prepared pan-genotypic primers and have been working. Next, we investigated the presence of viral genome mutations representing important predictive markers for HCC in patients with chronic HBV infection. In the cross-sectional analysis, 445 patients were divided according to HCC history and the influence of the viral protein markers. Patients with a history of HCC were found frequently in the low HBsAg group and high HBcrAg group, indicating that preS/S mutants could cause an imbalance of surface protein synthesis resulting in intracellular accumulation and extracellular decrease of HBsAg proteins, and leading to hepatocyte carcinogenesis.

Academic Significance and Societal Importance of the Research Achievements

現在の治療戦略では、B型肝炎ウイルス(HBV)根絶に不可欠なcccDNAを制御することはできず、HBV関連肝細胞癌(HCC)発症も制御できず、HCC早期発見の手段も限定的である。本研究は、細胞内におけるHBVゲノム変異ないし組み換えに着目した治療戦略の可能性を模索し、その結果としてHBs抗原タンパクの変異がHCC発症と関連する可能性を見出した。従来から提唱されていたHCCリスク集団とは異なり、新たなHCCリスクのサロゲートマーカーに繋がる可能性があり、社会的意義は大きく、さらに宿主ゲノムへのHBVインテグレーション解析の重要性が再認識されたことから、学術的意義も高いと考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2019 2017 2016

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] 首都圏におけるB型急性肝炎の変遷:Genotype Aの急増から10年を経て2019

    • Author(s)
      山田典栄,平石哲也,池田裕喜,渡邊綱正,奥瀬千晃, 今井康晴,四柳宏,加藤孝宣,鈴木通博,安田清美
    • Journal Title

      肝臓

      Volume: 印刷中

    • NAID

      130007650443

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship of hepatitis B virus infection to the recurrence of hepatocellular carcinoma after direct acting antivirals.2017

    • Author(s)
      Shimizu H, Matsui K, Iwabuchi S, Fujikawa T, Nagata M, Takatsuka K, Tanemura H, Nakazaki H, Nakano M, Watanabe T.
    • Journal Title

      Indian J Gastroenterol.

      Volume: 36 Issue: 3 Pages: 235-238

    • DOI

      10.1007/s12664-017-0755-3

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 先行する核酸アナログ製剤からテノホビルへの変更が HBs 抗原量に及ぼす影響2017

    • Author(s)
      奥瀬千晃, 平石哲也, 石井俊哉, 森田望, 末谷敬吾, 石郷岡晋也, 池田裕喜, 渡邊綱正, 松永光太郎, 松本伸行, 高橋秀明, 四柳宏, 伊東文生, 鈴木通博
    • Journal Title

      肝臓

      Volume: 58 Pages: 354-356

    • NAID

      130006855887

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] アメーバ性大腸炎に続発したB 型急性肝炎の1 例2017

    • Author(s)
      薩田祐輔, 平石哲也, 奥瀬千晃, 鈴木達也, 森田望, 末谷敬吾, 中野弘康, 石郷岡晋也, 石井俊哉, 高橋秀明, 池田裕喜, 渡邊綱正, 松永光太郎, 松本伸行, 四柳宏, 伊東文生, 鈴木通博
    • Journal Title

      肝臓

      Volume: 58 Pages: 626-631

    • NAID

      130006225004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Virological characteristics of hepatitis B genotype G/A2 recombination virus in Japan.2016

    • Author(s)
      Tsuzuki Y, Watanabe T, Iio E, Fujisaki S, Ibe S, Kani S, Hamada-Tsutsumi S, Yokomaku Y, Iwatani Y, Sugiura W, Okuse C, Okumura A, Sato Y, Tanaka Y.
    • Journal Title

      Hepatol Res.

      Volume: 印刷中 Issue: 8 Pages: 75-783

    • DOI

      10.1111/hepr.12612

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of de novo hepatitis B in patient during follow-up of liver-graft-versus-host disease associated with allogeneic peripheral blood stem cell transplantation.2016

    • Author(s)
      Michikawa Y, Ikeda H, Okuse C, Okano M, Shigefuku R, Hattori N, Hatsugai M, Takahashi H, Matsunaga K, Watanabe T, Matsumoto N, Yotsuyanagi H, Suzuki M, Itoh F.
    • Journal Title

      Case Rep Inter Med.

      Volume: 3 Issue: 1 Pages: 16-20

    • DOI

      10.5430/crim.v3n1p16

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 新規核酸アナログ4’-C-cyano-2-amino-2’-deoxyadenosine, 4’-C-cyano-2’-deoxyguanosine は薬剤耐性B 型肝炎ウイルス変異株に 対して有効である2016

    • Author(s)
      林佐奈衣, 高松悠樹, 前田賢次, 村上周子, 尾曲克己, 松居剛志, 五十川正記, 渡邊綱正, 狩野吉康, 向後悟, 満屋裕明, 田中靖人
    • Journal Title

      肝臓

      Volume: 57 Pages: 299-301

    • NAID

      130005160949

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] HIV-1 感染急性期におけるサイトカインのプロファイル解析.2016

    • Author(s)
      重見麗, 蜂谷敦子, 松田昌和, 岡﨑玲子, 小川慎太郎, 伊藤恭子, 健山正男, 今村顕史, 栁澤邦雄, 矢野邦夫, 藤井輝久, 上田敦久, 今村淳治, 渡邊綱正, 田中靖人, 横幕能行, 杉浦亙, 岩谷靖雅
    • Journal Title

      日本エイズ学会誌

      Volume: 18 Pages: 154-162

    • NAID

      40020856373

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] HBs 抗原消失を目標とした治療法の試み~肝炎応答と HBs 抗原減少の関連~2016

    • Author(s)
      渡邊綱正, 山田典栄, 奥瀬千晃, 池田裕喜, 松本伸行, 中野弘康, 平石哲也, 重福隆太, 服部伸洋, 松永光太郎, 小林稔, 安田清美, 四柳宏, 鈴木通博, 伊東文生
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ幕張(千葉県千葉市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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