Development of the method for the prevention of the chronicity of hepatitis B virus infection using two types of next generation sequencer

• Project/Area Number: 24591002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Aichi Medical University
• Principal Investigator: ITO Kiyoaki 愛知医科大学, 医学部, 准教授 (50551420)
• Co-Investigator(Kenkyū-buntansha): MIZOKAMI Masashi 独立行政法人国立国際医療研究センター, その他部局等, その他 (40166038) ; SUGIYAMA Masasya 独立行政法人国立国際医療研究センター, その他部局等, その他 (20612427)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); 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)
• Keywords: B型肝炎 / 急性肝炎 / 慢性化 / 次世代シーケンサー / HLA / 遺伝子変異 / genotype A / quasispecies / SNPs / B型急性肝炎 / ジェノタイプ / B型慢性肝炎

Outline of Final Research Achievements

We have reported that the chronicity rate after acute hepatitis B (AHB) with genotype A is 7-8%. On the other hand, the chronicity rate of AHB with non-A genotypes was less than 1% (Ito K et al. Hepatology, 2014). It is important to find the method for preventing chronicity after AHB, otherwise they would be at risk for progression to severe liver diseases such as liver cirrhosis or hepatocellular carcinoma. In this research, we have found that the new insights by approaching both from the host factors and from viral factors using next generation sequencer. As a host factor, one of the HLA-DPB locus was associated with the chronicity after AHB.The temporal emergence of the specific mutation, as a viral factor, was associated with chronicity after AHB by the result of long read type next generation sequencer. Our findings should be becoming the basis for the future treatment against hepatitis B virus infection.

Research Products

• [Journal Article] Multicenter cooperative case survey of Hepatitis B virus reactivation by chemotherapeutic agents. (2015)
  • Author(s): Takahashi H, Ikeda M, Kumada T, Osaki Y, Kondo S, Kusumoto S, Ohkawa K, Nadano S, Furuse J, Kudo M, Ito K, Yokoyama M, Okusaka T, Shimoyama M, Mizokami M
  • Journal Title: Hepatol Res Volume: Jan 27 Issue: 12 Pages: 1220-1227
  • DOI: 10.1111/hepr.12496
  • Peer Reviewed
• [Journal Article] Use of nucleotide analogs in patients with chronic hepatitis B in Nepal: A prospective cohort study in a single hospital. (2015)
  • Author(s): Masaki N, Shrestha PK, Nishimura S, Ito K, Sugiyama M, Mizokami M
  • Journal Title: Hepatol Res Volume: Jan 12 Issue: 12 Pages: 1163-1169
  • DOI: 10.1111/hepr.12482
  • Peer Reviewed
• [Journal Article] Pretreatment prediction of the outcome of response-guided peginterferon-α and ribavirin therapy for chronic hepatitis C (2014)
  • Author(s): Masaki N, Sugiyama M, Shimada N, Tanaka Y, Nakamuta M, Izumi N, Watanabe S, Tsubota A, Komatsu M, Masaki T, Enomoto N, Yoneda M, Murata K, Ito K, Koike K, Mizokami M.
  • Journal Title: J Gastroenterol Hepatol Volume: 29 Issue: 12 Pages: 1996-2005
  • DOI: 10.1111/jgh.12646
  • Peer Reviewed
• [Journal Article] Risk factors for long-term persistence of serum hepatitis B surface antigen following acute hepatitis B virus infection in Japanese adults (2014)
  • Author(s): Ito K, Yotsuyanagi H, Yatsuhashi H, Karino Y, Takikawa Y, Saito T, Arase Y, Imazeki F, Kurosaki M, Umemura T, Ichida T, Toyoda H, Yoneda M, Mita E, Yamamoto K, Michitaka K, Maeshiro T, Tanuma J, Tanaka Y, Sugiyama M, Murata K, Masaki N, Mizokami M; Japanese AHB Study Group
  • Journal Title: Hepatology Volume: 59 Issue: 1 Pages: 89-97
  • DOI: 10.1002/hep.26635
  • Peer Reviewed
• [Journal Article] ウイルス学的解析が可能であったHBs抗原陰性B型急性肝不全の１例 (2014)
  • Author(s): 近藤力、伊藤清顕、中出幸臣、山本高也、小林佑次、大橋知彦、石井紀光、佐藤顕、中尾春壽、福沢嘉孝、米田政志
  • Journal Title: 肝臓 Volume: 未定
  • NAID: 130004678872
  • Peer Reviewed
• [Journal Article] High levels of hepatitis B virus after the onset of disease lead to chronic infection in patients with acute hepatitis B. (2013)
  • Author(s): Yotsuyanagi H, Ito K, Yamada N, Takahashi H, Okuse C, Yasuda K, Su¬zuki M, Moriya K, Mizokami M, Miyakawa Y, Koike K.
  • Journal Title: Clinical Infectious Diseases Volume: 57 Issue: 7 Pages: 935-942
  • DOI: 10.1093/cid/cit348
  • Peer Reviewed
• [Journal Article] A Serum A"sweet-doughnut" protein facilitates fibrosis evaluation and therapy assessment in patients with hepatitis. (2013)
  • Author(s): Kuno A, Ikehara Y, Tanaka Y, Ito K, Matsuda A, Sekiya S, Hige S, Sakamoto M, Kage M, Mizokami M, Narimatsu H
  • Journal Title: Sci Rep Volume: 3 Issue: 1 Pages: 1065-1065
  • DOI: 10.1038/srep01065
  • Peer Reviewed
• [Journal Article] No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations. (2012)
  • Author(s): Sawai H, Asahina Y, Tokunaga K et al
  • Journal Title: BMC Med Genet Volume: 13 Issue: 1 Pages: 47-47
  • DOI: 10.1186/1471-2350-13-47
  • Peer Reviewed
• [Presentation] Development of New Anti-Viral Agent Targeting Sugar Chain Synthesis System Associated with Life cycle of Hepatitis B Virus. (2014)
  • Author(s): Ito K, Yoneda M, Angata K, Tong S, Mizokami M, Narimatsu H
  • Organizer: 2014 International Meeting on Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Los Angeles, USA
  • Year and Date: 2014-09-03 – 2014-09-06
• [Presentation] B型急性肝炎の慢性化に関する検討 (2013)
  • Author(s): 伊藤清顕、四柳宏、溝上雅史
  • Organizer: 第40回日本肝臓学会西部会
  • Place of Presentation: 岐阜
• [Presentation] Risk factors for long-term persistence of serum hepatitis B surface antigen following acute hepatitis B virus infection in Japanese adults. (2013)
  • Author(s): Ito K, Yotsuyanagi H, Yatsuhashi H, Krino Y, Takikawa Y, Saito T, Arase Y, Imazeki F, Kurosaki M, Umemura T, Ichida T, Toyoda H, Yoneda M, Mita E, Yamamoto K, Michitaka K, Meshiro T, Tanuma J, Tanaka Y, Sugiyama M, Murata K, Masaki N, Mizokami M
  • Organizer: The 64th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Washington DC, USA
• [Presentation] HBVジェノタイプの最近の動向と病態との関連 (2013)
  • Author(s): 伊藤清顕、溝上雅史
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 鹿児島
• [Presentation] B型慢性肝炎に関する全国調査結果
  • Author(s): 伊藤清顕、溝上雅史
  • Organizer: 第20回日本消化器関連学会週間JDDW2012シンポジウム
  • Place of Presentation: 神戸
• [Book] MEDICAL TECHNOLOGY 肝炎ウイルスマーカーの読み方 ＜特集＞B型・C型肝炎治療における臨床検査の役割 ウイルス肝炎の診断・治療のための臨床検査 (2014)
  • Author(s): 伊藤清顕
  • Total Pages: 7
  • Publisher: 医歯薬出版
• [Book] 第29回 犬山シンポジウム記録集 B型急性肝炎および慢性肝疾患におけるHBVゲノタイプAの頻度と感染経路の検討 (2013)
  • Author(s): 鈴木一幸、滝川康裕、遠藤龍人、宮坂昭生、宮本康弘、小野寺美緒、小山富子、岡本宏明、伊藤清顕、溝上雅史
  • Total Pages: 6
  • Publisher: メディカルトリビューン
• [Book] コホート研究からみたウイルス性肝炎の解明 全国調査からみたB型慢性肝炎の病態 (2013)
  • Author(s): 伊藤清顕、溝上雅史
  • Total Pages: 9
  • Publisher: メディカルレビュー社
• [Book] 化学療法の領域増刊号 HBV遺伝子型とB型急性肝炎 (2012)
  • Author(s): 伊藤清顕、溝上雅史
  • Total Pages: 9
  • Publisher: 医薬ジャーナル社
• [Book] 医学のあゆみ B型肝炎ー最新治療コンセンサス Genotype AによるB型急性肝炎の拡大とその特徴 (2012)
  • Author(s): 伊藤清顕、溝上雅史
  • Total Pages: 6
  • Publisher: 医歯薬出版株式会社