New graft preservation for the improvement of donation after cardiac death liver graft function.

• Project/Area Number: 20K17580
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyoto University
• Principal Investigator: Okumura Shinya 京都大学, 医学研究科, 助教 (70830032)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 臓器保存 / 心停止肝移植

Outline of Research at the Start

心停止後ドナーからの肝移植（心停止肝移植）はドナーの不足を補う新しい肝移植医療として注目されているが、肝臓（グラフト）の虚血時間が長く、移植肝が長時間の低酸素状態にさらされる。そのため、移植後の肝障害（虚血再灌流障害）が強く、グラフトの機能不全や虚血性胆管障害を高率に発症し、予後不良である。本研究では、ラットおよびブタの心停止肝移植モデルを用いて、心停止肝グラフトの機能改善を目指した新しい臓器保存法の開発を行う。臓器摘出前後および臓器保存中に、グラフト肝に効率的な酸素化を行うことで、心停止肝グラフト機能の改善を目指す。

Outline of Final Research Achievements

The outcome of donation after cardiac death (DCD) liver transplantation is worse compared with that of donation after brain death liver transplantation due to the long hypoxic period of donor warm ischemic time. We investigated the impact of improved graft oxygenation on liver ischemia-reperfusion injury (IRI) and survival after DCD liver transplantation. Biochemical and histopathologic analysis showed that liver graft preservation with oxygenation attenuated liver IRI and improved postoperative survival.

Academic Significance and Societal Importance of the Research Achievements

心停止後ドナーからの肝移植（心停止肝移植）はドナーの不足を補う新しい肝移植医療として注目されているが、肝臓（グラフト）の虚血時間が長くなることから、移植肝が長時間の低酸素状態にさらされる。
臓器保存液の酸素化を行う新規臓器保存法を取り入れることで、心停止肝移植の問題点である肝グラフトの虚血再灌流障害を軽減することができ、将来的に救命できる患者数を増加させることができる。

Research Products

• [Journal Article] Venous outflow reconstruction in living‐donor liver transplantation for Budd?Chiari syndrome involving vena cava (2024)
  • Author(s): Hata Koichiro、Nishio Takahiro、Kumagai Motoyuki、Masano Yuki、Kageyama Shoichi、Okumura Shinya、Ito Takashi、Yamazaki Kazuhiro、Minatoya Kenji、Hatano Etsuro
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: Online ahead of print Issue: 8
  • DOI: 10.1002/jhbp.1430
• [Journal Article] Left-sided major hepatectomy with en bloc resection of the hepatoduodenal ligament utilizing a liver-transection first approach: A video vignette (2024)
  • Author(s): Ishii Takamichi、Ito Takashi、Okumura Shinya、Hatano Etsuro
  • Journal Title: Asian Journal of Surgery Volume: 47 Issue: 1 Pages: 497-498
  • DOI: 10.1016/j.asjsur.2023.04.071
• [Journal Article] Impact of thoracic shape on the surgical outcomes of laparoscopic‐assisted living donor hepatectomy (2023)
  • Author(s): Tanaka Kosuke、Ogiso Satoshi、Yoh Tomoaki、Abdelhafez Ahmed Hussein、Masano Yuki、Okumura Shinya、Kageyama Shoichi、Ito Takashi、Hata Koichiro、Hatano Etsuro
  • Journal Title: Annals of Gastroenterological Surgery Volume: 8 Issue: 3 Pages: 490-497
  • DOI: 10.1002/ags3.12755
• [Journal Article] Effects of Adding Congested Segment IV to the Left Lateral Graft on Short-term Outcomes in Pediatric Living-donor Liver-transplant Recipients (2023)
  • Author(s): Aoki Hikaru、Ito Takashi、Hirata Masaaki、Kadohisa Masashi、Yamamoto Miki、Uebayashi Elena Yukie、Shirai Hisaya、Okumura Shinya、Masano Yuki、Ogawa Eri、Okamoto Tatsuya、Okajima Hideaki、Hatano Etsuro
  • Journal Title: Transplantation Direct Volume: 9 Issue: 11 Pages: e1551-e1551
  • DOI: 10.1097/txd.0000000000001551
• [Journal Article] A circulating subset of iNKT cells mediates antitumor and antiviral immunity (2022)
  • Author(s): Cui G, Shimba A, et.al
  • Journal Title: Science Immunology Volume: 7 Issue: 76 Pages: 8760-8760
  • DOI: 10.1126/sciimmunol.abj8760
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Stepwise approach for acquisition of microsurgical skills through rat orthotopic liver transplantation experiments (2022)
  • Author(s): Hirata Masaaki、Yagi Shintaro、Ito Takashi、Masano Yuki、Okumura Shinya、Yao Siyuan、Miyachi Yosuke、Aoki Hikaru、Katano Kaoru、Hatano Etsuro
  • Journal Title: European Surgical Research Volume: - Issue: 2 Pages: 310-314
  • DOI: 10.1159/000528092
  • Peer Reviewed
• [Journal Article] 肝動脈塞栓症（HAT） (2022)
  • Author(s): 奧村晋也、伊藤孝司、小川絵里、波多野悦朗
  • Journal Title: 臨床外科 Volume: 77 Pages: 268-275
• [Journal Article] Pretransplant Body Composition Abnormality Has a Negative Impact Especially on Living Donor Liver Transplantation (2021)
  • Author(s): Shinya Okumura, Shintaro Yagi, Yuhei Hamaguchi, Yuji Yoshioka, Siyuan Yao, Naoko Kamo, Kojiro Taura, Toshimi Kaido, Shinji Uemoto
  • Journal Title: Transplantation Volume: 105 Issue: 3 Pages: e37-e38
  • DOI: 10.1097/tp.0000000000003562
  • Peer Reviewed
• [Journal Article] Etiology of Liver Steatosis Influences the Severity of Ischemia/Reperfusion Injury and Survival After Liver Transplantation in Rats (2020)
  • Author(s): Miyachi Yosuke、Yagi Shintaro、Hirata Masaaki、Iwamura Sena、Yao Siyuan、Shirai Hisaya、Okumura Shinya、Iida Taku、Ito Takashi、Uozumi Ryuji、Kaido Toshimi、Uemoto Shinji
  • Journal Title: Liver Transplantation Volume: 26 Issue: 11 Pages: 1504-1515
  • DOI: 10.1002/lt.25814
  • Peer Reviewed
• [Journal Article] Including body composition in MELD scores improves mortality prediction among patients awaiting liver transplantation. (2019)
  • Author(s): Hamaguchi Y, Kaido T, Okumura S, Kobayashi A, Shirai H, Yao S, Yagi S, Kamo N, Uemoto S
  • Journal Title: Clin Nutr Volume: in press Issue: 6 Pages: 1885-1892
  • DOI: 10.1016/j.clnu.2019.08.012
  • Peer Reviewed