Innovative Preservation of Steatotic Liver Grafts using Carbon Monoxide

• Project/Area Number: 15H04919
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Kyoto University
• Principal Investigator: Uemoto Shinji 京都大学, 医学研究科, 教授 (40252449)
• Co-Investigator(Kenkyū-buntansha): 秦 浩一郎 京都大学, 医学研究科, 助教 (90523118)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 臓器保存 / 脂肪肝 / 一酸化炭素 / 水素 / 虚血再灌流傷害 / Medical Gas / 灌流保存 / 肝移植 / 虚血再灌流 / 高圧気相保存 / 虚血再灌流障害 / 高圧気相保存法

Outline of Final Research Achievements

Due to the toxicity of carbon monoxide (CO), the research was not permitted in our animal center, we tried to get our own laboratory, obtained, and started the research. However, we’re supposed to equip a powerful draft chamber with exhaust duct to the top of the building, so that the circumstances were ready in the last year of the study period. We obtained promising results in fatty liver preservation by hyperbaric CO+O2, however, the time was over before getting significant results. During the preparation of laboratory/ equipments, subnormothermic machine perfusion (SMP) preservation, as well as non-toxic materials were investigated, including hydrogen gas (H2), human atrial natriuretic peptide (hANP) and recombinant AT-III. We already published significant protection in preservation of severe steatotic livers by SMP. We also demonstrated the efficacy of H2 against hepatic ischemia/reperfusion, hANP, and rAT-III in DCD liver grafts, all of which are now ready to publication.

Research Products

• [Int'l Joint Research] Institute for Laboratory Animal Science/RWTH Aachen University/Germany(ドイツ)
• [Int'l Joint Research]
• [Journal Article] Impact of Donor Age on Recipient Survival in Adult-to-adult Living-donor Liver Transplantation. (2017)
  • Author(s): Kubota T, Hata K, Sozu T, Ueda Y, Hirao H, Okamura Y, Tamaki I, Yoshikawa J, Kusakabe J, Uemoto S, et al.
  • Journal Title: Annals of Surgery Volume: In Press Issue: 6 Pages: 1126-1133
  • DOI: 10.1097/sla.0000000000002194
  • Peer Reviewed
• [Journal Article] Reply to "Representing Subnormothermic Machine Perfusion in Fatty Livers: The Complete Picture?" (2017)
  • Author(s): Okamura Y, Hata K, Uemoto S.
  • Journal Title: American Journal of Transplantation Volume: In Press Issue: 5 Pages: 1423-1424
  • DOI: 10.1111/ajt.14254
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting. (2017)
  • Author(s): Okamura Y, Hata K, Tanaka H, Hirao H, Kubota T, Inamoto O, Kageyama S, Tamaki I, Yermek N, Yoshikawa J, Uemoto S.
  • Journal Title: American Journal of Transplantation Volume: In Press Issue: 5 Pages: 1204-1215
  • DOI: 10.1111/ajt.14110
  • Peer Reviewed / Open Access
• [Journal Article] 境界グラフトの健常性維持と機能再生を目指した移植肝臓器保存戦略 (2017)
  • Author(s): 秦浩一郎, 岡村裕輔, 玉木一路, 後藤徹, Yermek Nigmet, 日下部治郎, 吉川潤一, 田嶋哲也, 稲本道, 久保田豊成, 平尾浩史, 影山詔一, 田中宏和, 上本伸二
  • Journal Title: Organ Biology Volume: 24巻2号
  • Peer Reviewed
• [Journal Article] Portal vein reconstruction using vein grafts in pediatric living donor liver transplantation: Current status. (2017)
  • Author(s): Sabra TA, Okajima H, Yoshizawa A, Okamoto T, Anazawa T, Ygi S, Hata K, Yasuchika K, Taura K, Hatano E, Kaido T, Uemoto S.
  • Journal Title: Pediatric Transplantation Volume: In Press Issue: 3
  • DOI: 10.1111/petr.12888
  • Peer Reviewed
• [Journal Article] Influence of hepatorenal syndrome on outcome of living donor liver transplantation: A single-center experience in 357 patients. (2017)
  • Author(s): Okamura Y, Hata K, Inamoto O, Kubota T, Hirao H, Tanaka H, Fujimoto Y, Ogawa K, Mori A, Okajima H, Kaido T, Uemoto S.
  • Journal Title: Hepatology Research Volume: 47 Issue: 5 Pages: 425-434
  • DOI: 10.1111/hepr.12764
  • Peer Reviewed
• [Presentation] Postoperative Thrombocytopenia (< 2 weeks) Determines the Fate of Adult LDLT: Proposal of “LTx-TMA”. (2017)
  • Author(s): Koichiro Hata, Hirokazu Tanaka, Kayoko Endo, Jiro Kusakabe, Ichiro Tamaki, Tetsuya Tajima, Toru Goto, Junichi Yoshikawa, Takashi Ito, Atsushi Yoshizawa, Shintaro Yagi, Hideaki Okajima, Toshimi Kaido, Akira Shimizu, and Shinji Uemoto.
  • Organizer: The 9th Meeting of 5 Asian LDLT Centers, 21st Oct. 2017, Kyoto, Japan.
  • Int'l Joint Research
• [Presentation] Hydrogen Perfusion after Cold Storage; A New, Simple, and Non-invasive Graft Conditioning for Ameliorating Hepatic Ischemia/Reperfusion Injury? (2017)
  • Author(s): Ichiro Tamaki, Koichiro Hata, Yusuke Okamura, Nigmet Yermek, Hirofumi Hirao, Toyonari Kubota, Osamu Inamoto, Jiro Kusakabe, Junichi Yoshikawa, Tetsuya Tajima, Toru Goto, and Shinji Uemoto.
  • Organizer: The 18th Congress of the European Society for Organ Transplantation (ESOT), 24-27 Sep. 2017, Barcelona, Spain.
  • Int'l Joint Research
• [Presentation] Hydrogen Perfusion after Cold Storage; A New, Simple, and Non-invasive Post-Conditioning for Ameliorating Hepatic Ischemia/Reperfusion Injury? (2017)
  • Author(s): Ichiro Tamaki, Koichiro Hata, Yusuke Okamura, Nigmet Yermek, Hirofumi Hirao, Toyonari Kubota, Osamu Inamoto, Jiro Kusakabe, Junichi Yoshikawa, Hirokazu Tanaka, Shoichi Kageyama, Tetsuya Tajima, Toru Goto, and Shinji Uemoto.
  • Organizer: The 52nd meeting of the European Society for Surgical Research (ESSR), 14-17 June 2017, Amsterdam, the Netherlands.
  • Int'l Joint Research
• [Presentation] Efficacy of the novel Preservation Solution, Ecosol, in a rat liver transplantation model. (2017)
  • Author(s): TANAKA Hirokazu, Doorschodt BMD, Fukushima FK, Assar AMAM, Kadaba Srinivasan, Pawlowsky KP, Hata KH, Tolba RT.
  • Organizer: The 52nd meeting of the European Society for Surgical Research (ESSR), 14-17 June 2017, Amsterdam, the Netherlands.
  • Int'l Joint Research
• [Presentation] V5 & V8 Reconstruction in Right-lobe Living-Donor Liver Transplantation; Our Standardized Procedures and Recent Modification of “half-circumferential anastomosis”. (2017)
  • Author(s): Koichiro Hata, Tetsuya Tajima, Takayuki Anazawa, Atsushi Yoshizawa, Shintaro Yagi, Hideaki Okajima, Toshimi Kaido, and Shinji Uemoto.
  • Organizer: The 6th Biennial Congress of the Asian-Pacific Hepato-Pancreato-Biliary Association, 7-10, June 2017, Yokohama, Japan.
  • Int'l Joint Research
• [Presentation] Postoperative Low Platelet Count and Elevated Total Bilirubin Impact the Mortality and Morbidity in Living-donor Liver Transplantation. (2017)
  • Author(s): Jiro Kusakabe, Koichiro Hata, Yusuke Okamura, Ichiro Tamaki, Nigmet Yermek, Junichi Yoshikawa, Tetsuya Tajima, Toru Goto, Hirokazu Tanaka, Hideaki Okajima, Toshimi Kaido, and Shinji Uemoto.
  • Organizer: 15th Congress of the Asian Society of Transplantation (CAST), 27-30 November 2017, Cebu, Philippines
  • Int'l Joint Research
• [Presentation] Bortezomib against Post-operative Antibody-Mediated Rejection in ABO-incompatible Living-Donor Liver Transplantation: Report of a Successful Case. (2017)
  • Author(s): Tetsuya Tajima, Koichiro Hata, Hideaki Okajima, Ken Fukumitsu, Atsushi Yoshizawa, Ichiro Tamaki, Nigmet Yermek, Jiro Kusakabe, Junichi Yoshikawa, Toru Goto and Shinji Uemoto
  • Organizer: 15th Congress of the Asian Society of Transplantation (CAST), 27-30 November 2017, Cebu, Philippines.
  • Int'l Joint Research
• [Presentation] 境界グラフトの健常性維持と機能再生を目指した移植肝臓器保存戦略 ～京都大学の取り組み～ (2016)
  • Author(s): 秦浩一郎，岡村裕輔，玉木一路，Nigmet Yermek, 田中宏和，平尾浩史，久保田豊成，稲本道，吉川潤一，上本伸二
  • Organizer: 第43回 臓器保存生物医学会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-26
  • Invited
• [Presentation] 移植肝冷保存後の経門脈的水素灌流は、冷虚血/温再灌流障害を軽減する (2016)
  • Author(s): 玉木 一路（1，秦 浩一郎（1，岡村 裕輔（1，Nigmet Ermek（1,平尾 浩史（1，久保田 豊成（1，稲本 道（1,吉川 潤一（1上本 伸二（1
  • Organizer: 第43回 臓器保存生物医学会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-26
  • Invited
• [Presentation] Protection of Donation after Cardiac Death Livers during Cold Storage with Human Atrial Natriuretic Peptide (ANP) (2016)
  • Author(s): Nigmet Yermek, Koichiro Hata, Yusuke Okamura, Ichiro Tamaki, Shinji Uemoto,, et al.
  • Organizer: 第43回 臓器保存生物医学会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-26
  • Invited
• [Presentation] 再（再々）肝移植例に対する脳死ドナー肝の配分の是非 ～自験110例の解析から～ (2016)
  • Author(s): 秦浩一郎、田嶋哲也、穴澤貴行、八木真太郎、吉澤淳、山敷宣代、岡島英明、海道利実、上本伸二
  • Organizer: 第 52回 日本移植学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-09-30
  • Invited
• [Presentation] Impact of Hepatorenal Syndrome on Outcome of Living Donor Liver Transplantation: A Single-Center Experience in 357 Patients (2016)
  • Author(s): Yusuke Okamura, Koichiro Hata, Ichiro Tamaki, Nigmet Yermek, and Shinji Uemoto, et al.
  • Organizer: TTS 2016（国際移植学会）
  • Place of Presentation: Hong Kong（香港）
  • Year and Date: 2016-08-21
  • Int'l Joint Research / Invited
• [Presentation] Post-operative thrombocytopenia determines the fate of adult-to-adult living donor partial liver transplantation; Proposal of “Thrombotic Microangiopathy (LTx-TMA) Score” (2016)
  • Author(s): Koichiro Hata, Hirokazu Tanaka, Kayoko Endo, Hirofumi Hirao, Yusuke Okamura, Akira Shimizu, and Shinji Uemoto, et al.
  • Organizer: TTS 2016（国際移植学会）
  • Place of Presentation: Hong Kong（香港）
  • Year and Date: 2016-08-20
  • Int'l Joint Research / Invited
• [Presentation] 肝移植後早期の血小板減少は肝移植予後を規定する ～”LTx-TMA Scoring”の提唱～ (2016)
  • Author(s): 秦浩一郎、田中宏和、平尾浩史、久保田豊成、岡村裕輔、稲本道、玉木一路、Nigmet Yermek, 吉川潤一、岡島英明、海道利実、上本伸二
  • Organizer: 第34回 肝移植研究会
  • Place of Presentation: 旭川市
  • Year and Date: 2016-07-07
  • Invited
• [Presentation] 室温灌流保存-同所性ラット肝移植モデルの作成 (2016)
  • Author(s): 岡村裕輔，秦浩一郎，吉川潤一，Nigmet Yermek，玉木一路，稲本道，久保田豊成，平尾浩史，上本伸二
  • Organizer: 第34回 肝移植研究会
  • Place of Presentation: 旭川市
  • Year and Date: 2016-07-07
  • Invited
• [Presentation] 肝移植後C型肝炎に対するソホスブビル＋レジパスビル治療の効果と安全性 (2016)
  • Author(s): 上田 佳秀、秦 浩一郎、八木 真太郎、穴澤 貴行、吉澤 淳、山敷 宣代、海道 利実、岡島 英明、宮川 文、羽賀 博典、丸澤 宏之、妹尾 浩、上本 伸二
  • Organizer: 第34回 肝移植研究会
  • Place of Presentation: 旭川市
  • Year and Date: 2016-07-07
  • Invited
• [Presentation] 急性肝不全に対する肝移植周術期管理 ～高容量血液浄化法の役割と今後の課題～ (2016)
  • Author(s): 秦 浩一郎1)、塚本 達雄2)、山田 博之2)、宮田 仁美3)、八木 真太郎1)、山敷 宣代3)、岡島 英明1)、海道 利実1, 3)、柳田 素子2)、上本 伸二1)
  • Organizer: 第42回日本急性肝不全研究会
  • Place of Presentation: 千葉市
  • Year and Date: 2016-05-18
  • Invited
• [Presentation] 「肝摘出後、体外での健常性維持と機能再生を目指した肝灌流保存法の開発」 (2016)
  • Author(s): 秦浩一郎1、岡村裕輔1、田中宏和1, 2、玉木一路1、Nigmet Yermek1、平尾浩史1、久保田豊成1、稲本道1、岡島英明1、海道利実1、上本伸二1
  • Organizer: 第55回 日本生体医工学会
  • Place of Presentation: 富山市
  • Year and Date: 2016-04-26
  • Invited
• [Presentation] 室温灌流保存-同所性ラット全肝移植モデルの作成 (2015)
  • Author(s): 岡村 裕輔（1，秦 浩一郎（1，田中 宏和（1，玉木 一路（1，稲本 道（1,門野 賢太郎（1，久保田 豊成（1，平尾 浩史（1，上本 伸二（1
  • Organizer: 第42回 臓器保存生物医学会総会
  • Place of Presentation: 盛岡市
  • Year and Date: 2015-11-13
• [Presentation] 部分肝移植におけるADAMTS13の保護効果 ～ラット20%部分肝移植モデルを用いた検討～ (2015)
  • Author(s): 久保田 豊成（1，秦 浩一郎（1，田中 宏和（1，玉木 一路（1，稲本 道（1, 門野 賢太郎（1，岡村 裕輔（1，平尾 浩史（1，上本 伸二（1
  • Organizer: 第42回 臓器保存生物医学会総会
  • Place of Presentation: 盛岡市
  • Year and Date: 2015-11-13
• [Presentation] 常温/室温灌流保存による移植肝の健常性維持と機能再生 (2015)
  • Author(s): 秦浩一郎，岡村裕輔，田中宏和，平尾浩史，久保田豊成，稲本道，玉木一路、岡島英明、海道利実、上本伸二
  • Organizer: 第42回 臓器保存生物医学会総会
  • Place of Presentation: 盛岡市
  • Year and Date: 2015-11-13
  • Invited
• [Presentation] 当院における急性肝不全に対する初期治療アルゴリズム (2015)
  • Author(s): 秦 浩一郎、海道 利実、上本 伸二
  • Organizer: 第23回 JDDW
  • Place of Presentation: 東京
  • Year and Date: 2015-10-08
• [Presentation] 臓器移植法改正前後で再肝移植成績は変化したか？ 自験108例の解析から (2015)
  • Author(s): 秦浩一郎、久保田豊成、小川絵里、飯田拓、八木真太郎、吉澤淳、岡島英明、海道利実、上本伸二
  • Organizer: 第51回日本移植学会総会
  • Place of Presentation: 熊本市
  • Year and Date: 2015-10-01
• [Presentation] Subnormothermic Machine Perfusion Preservation of >30% Macro-steatotic Livers; (2015)
  • Author(s): Yusuke OKAMURA1, Koichiro HATA1, Hirokazu TANAKA1, Hirofumi HIRAO1, Toyonari KUBOTA1, Osamu INAMOTO1, Kentaro KADONO1, Shoichi KAGEYAMA1, Benedict M Doorschodt2, Rene H Tolba2, ,and Shinji UEMOTO1
  • Organizer: The 17th Congress of the European Society for Organ Transplantation
  • Place of Presentation: Brussels, Belgium
  • Year and Date: 2015-09-13
  • Int'l Joint Research
• [Presentation] Impact of Donor Age on the Outcome of Adult Living Donor Partial Liver Transplantation: Single-Center Experience in 316 Patients (2015)
  • Author(s): Toyonari Kubota1, Koichiro Hata1, Takashi Sozu2, Hirokazu Tanaka1, Hirofumi Hirao1, Yusuke Okamura1, Osamu Inamoto1, Kohei Ogawa1, Yasuhiro Fujimoto1, Akira Mori1, Hideaki Okajima1, Toshimi Kaido1, and Shinji Uemoto1
  • Organizer: The 17th Congress of the European Society for Organ Transplantation
  • Place of Presentation: Brussels, Belgium
  • Year and Date: 2015-09-13
  • Int'l Joint Research
• [Presentation] Impact of ADAMTS13, von Willebrand factor-cleaving protease, on hepatic ischemia/reperfusion injury (2015)
  • Author(s): Hirofumi Hirao, Koichiro Hata, Hirokazu Tanaka, Shoichi Kageyama, Yusuke Okamura, Toyonari Kubota, Osamu Inamoto, Kentaro Kadono, and Shinji Uemoto
  • Organizer: The 17th Congress of the European Society for Organ Transplantation
  • Place of Presentation: Brussels, Belgium
  • Year and Date: 2015-09-13
  • Int'l Joint Research
• [Presentation] Post-operative thrombocytopenia may determine the fate of adult-to-adult living donor partial liver transplantation; Proposal of “Thrombotic Microangiopathy (LTx-TMA) Score”. (2015)
  • Author(s): Hirokazu Tanaka, Koichiro Hata, Hirofumi Hirao, Yusuke Okamura, Toyonari Kubota, Osamu Inamoto, Shoichi Kageyama, Kohei Ogawa, Yasuhiro Fujimoto, Akira Mori, Hideaki Okajima, Toshimi Kaido, and Shinji Uemoto
  • Organizer: The 17th Congress of the European Society for Organ Transplantation
  • Place of Presentation: The 17th Congress of the European Society for Organ Transplantation
  • Year and Date: 2015-09-13
  • Int'l Joint Research
• [Presentation] 室温潅流保存は＞30%大滴性脂肪肝グラフトのPNFを抑制し、移植可能肝へと変貌させる (2015)
  • Author(s): 岡村裕輔，秦浩一郎，田中宏和，平尾浩史，久保田豊成，稲本道，門野賢太郎，影山詔一，上本伸二
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: 浜松市
  • Year and Date: 2015-07-15
• [Presentation] 臓器移植法改正がもたらした 急性肝不全に対する治療アルゴリズムの変化 (2015)
  • Author(s): 秦 浩一郎1)、宮田 仁美2)、山田 博之2)、八木 真太郎1)、藤本 康弘1)、小川 晃平1)、森 章1)、岡島 英明1)、海道 利実1)、塚本 達雄2)、柳田 素子2)、上本 伸二1)
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: 浜松市
  • Year and Date: 2015-07-15
• [Presentation] Subnormothermic Machine Perfusion Preservation of >30% Macro-steatotic Livers; (2015)
  • Author(s): Yusuke OKAMURA1, Koichiro HATA1, Hirokazu TANAKA1, Hirofumi HIRAO1, Toyonari KUBOTA1, Osamu INAMOTO1, Kentaro KADONO1, Shoichi KAGEYAMA1, Benedict M Doorschodt2, Rene H Tolba2, ,and Shinji UEMOTO1
  • Organizer: The ESSR (European Society for Surgical Research) 2015
  • Place of Presentation: Liverpool, UK
  • Year and Date: 2015-06-10
  • Int'l Joint Research
• [Presentation] 急性肝不全に対する初期治療アルゴリズムはどう変化したか？ (2015)
  • Author(s): 秦 浩一郎1)、塚本 達雄2)、山田 博之2)、宮田 仁美2)、八木 真太郎1)、飯田 拓1)、山敷宣代1)、藤本 康弘1)、小川 晃平1)、森 章1)、岡島 英明1)、海道 利実1)、柳田 素子2)、上本 伸二1)
  • Organizer: 第41回 急性肝不全研究会
  • Place of Presentation: 熊本市
  • Year and Date: 2015-05-20
• [Book] 「京大式肝臓外科のすべて」 (2015)
  • Author(s): 「京大式肝臓外科のすべて」作成委員会 （編集）, 上本 伸二 （監修）
  • Total Pages: 277
  • Publisher: 最新医学社