Research on the etiology and disease progression of biliary atresia focusing on various obstructive types and gene expression

• Project/Area Number: 17K11502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Tohoku University
• Principal Investigator: Sasaki Hideyuki 東北大学, 大学病院, 講師 (40438461)
• Co-Investigator(Kenkyū-buntansha): 田中 拡 東北大学, 医学系研究科, 大学院非常勤講師 (50579448) ; 仁尾 正記 東北大学, 医学系研究科, 教授 (70228138)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 胆道閉鎖症 / 病型 / 病因 / microRNA / 予後 / 肝臓 / マイクロアレイ

Outline of Final Research Achievements

In this study, we narrowed down candidates, which may be related to the pathogenesis and pathogenesis of biliary atresia in the comprehensive analysis so far, to four microRNAs by quantitative RT-PCR. As a result of investigating factors such as the four microRNAs, the age of initial surgery, disease type, and the clinical course, we found that cases can be stratified by the prognosis and the expression of intrahepatic microRNAs.
Therefore, we confirmed that the expression of intrahepatic microRNA has important significance in various pathological conditions of biliary atresia.

Academic Significance and Societal Importance of the Research Achievements

本研究では病型以外の手術日齢などの因子や臨床経過の検討を進めた結果、予後と肝内microRNAの発現により症例を層別化できることを見いだした。すなわち胆道閉鎖症の多彩な病態において肝内microRNAの発現が重要な意義を持つことが確認された。
本研究のデータをもとにさらに研究を進めることで、胆道閉鎖症の病因を明らかにして病態を解明できる可能性ならびにmicroRNAの発現パターンの相違と病型とを総合的に評価して術後治療の反応性を予測することにより、症例に応じた適切な術後治療の確立に繋がることが期待される。

Research Products

• [Journal Article] Impacts of Early K asai Portoenterostomy on Short‐Term and Long‐Term Outcomes of Biliary Atresia (2020)
  • Author(s): Okubo Ryuji、Nio Masaki、Sasaki Hideyuki、the Japanese Biliary Atresia Society
  • Journal Title: Hepatology Communications Volume: 5 Issue: 2 Pages: 234-243
  • DOI: 10.1002/hep4.1615
  • Peer Reviewed / Open Access
• [Journal Article] Clinical practice guidelines for biliary atresia in Japan: A secondary publication of the abbreviated version translated into English (2020)
  • Author(s): Ando Hisami、Inomata Yukihiro、Iwanaka Tadashi、Kuroda Tatsuo、Nio Masaki、Matsui Akira、Yoshida Masahiro、Sasaki Hideyuki、 The Japanese Biliary Atresia Society
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 28 Issue: 1 Pages: 55-61
  • DOI: 10.1002/jhbp.816
  • Peer Reviewed
• [Presentation] 当科の胆道閉鎖症における移行期医療の現状について (2020)
  • Author(s): 佐々木 英之、大久保龍二、和田基、福澤太一、工藤博典、安藤亮、橋本昌俊、遠藤悠紀、仁尾正記
  • Organizer: 第47回日本胆道閉鎖症研究会
• [Presentation] A relationship between microRNA expression and clinical course in biliary atresia (2018)
  • Author(s): Hideyuki Sasaki
  • Organizer: 51st Annual Scientific Meeting of the Pacific Association of Pediatric Surgeons
  • Int'l Joint Research
• [Presentation] 胆道閉鎖症肝組織におけるmicroRNAの発現と臨床経過についての検討 (2017)
  • Author(s): 佐々木英之
  • Organizer: 第44回日本胆道閉鎖症研究会