Ischaemia-free liver transplantation in humans: a first-in-human trial
Summary: Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences.Methods Ischaemia-free liver tra...
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2021-11-01
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Series: | The Lancet Regional Health. Western Pacific |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2666606521001693 |
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Zhiyong Guo, M.D., Ph.D. Qiang Zhao, M.D., Ph.D. Shanzhou Huang, M.D., Ph.D. Changjun Huang, M.D. Dongping Wang, M.D., Ph.D. Lu Yang, M.D., Ph.D. Jian Zhang, M.Sc. Maogen Chen, M.D., Ph.D. Linwei Wu, M.D., Ph.D. Zhiheng Zhang, M.D. Zebin Zhu, M.D., Ph.D. Linhe Wang, M.D. Caihui Zhu, M.D. Yixi Zhang, M.D., Ph.D. Yunhua Tang, M.D., Ph.D. Chengjun Sun, M.D. Wei Xiong, M.D. Yuekun Shen, M.D., Ph.D. Xiaoxiang Chen, M.D. Jinghong Xu, M.D. Tielong Wang, M.D. Yi Ma, M.D., Ph.D. Anbin Hu, M.D., Ph.D. Yinghua Chen, M.D., Ph.D. Xiaofeng Zhu, M.D., Ph.D. Jian Rong, M.D., Ph.D. Changjie Cai, M.D., Ph.D. Fengqiu Gong, M.P.H. Xiangdong Guan, M.D., Ph.D. Wenqi Huang, M.D., Ph.D. Dicken Shiu-Chung Ko, M.D., Ph.D. Xianchang Li, M.D., Ph.D. Stefan G Tullius, M.D., Ph.D. Jiefu Huang, M.D., Ph.D. Weiqiang Ju, M.D., Ph.D. Xiaoshun He, M.D., Ph.D. |
spellingShingle |
Zhiyong Guo, M.D., Ph.D. Qiang Zhao, M.D., Ph.D. Shanzhou Huang, M.D., Ph.D. Changjun Huang, M.D. Dongping Wang, M.D., Ph.D. Lu Yang, M.D., Ph.D. Jian Zhang, M.Sc. Maogen Chen, M.D., Ph.D. Linwei Wu, M.D., Ph.D. Zhiheng Zhang, M.D. Zebin Zhu, M.D., Ph.D. Linhe Wang, M.D. Caihui Zhu, M.D. Yixi Zhang, M.D., Ph.D. Yunhua Tang, M.D., Ph.D. Chengjun Sun, M.D. Wei Xiong, M.D. Yuekun Shen, M.D., Ph.D. Xiaoxiang Chen, M.D. Jinghong Xu, M.D. Tielong Wang, M.D. Yi Ma, M.D., Ph.D. Anbin Hu, M.D., Ph.D. Yinghua Chen, M.D., Ph.D. Xiaofeng Zhu, M.D., Ph.D. Jian Rong, M.D., Ph.D. Changjie Cai, M.D., Ph.D. Fengqiu Gong, M.P.H. Xiangdong Guan, M.D., Ph.D. Wenqi Huang, M.D., Ph.D. Dicken Shiu-Chung Ko, M.D., Ph.D. Xianchang Li, M.D., Ph.D. Stefan G Tullius, M.D., Ph.D. Jiefu Huang, M.D., Ph.D. Weiqiang Ju, M.D., Ph.D. Xiaoshun He, M.D., Ph.D. Ischaemia-free liver transplantation in humans: a first-in-human trial The Lancet Regional Health. Western Pacific |
author_facet |
Zhiyong Guo, M.D., Ph.D. Qiang Zhao, M.D., Ph.D. Shanzhou Huang, M.D., Ph.D. Changjun Huang, M.D. Dongping Wang, M.D., Ph.D. Lu Yang, M.D., Ph.D. Jian Zhang, M.Sc. Maogen Chen, M.D., Ph.D. Linwei Wu, M.D., Ph.D. Zhiheng Zhang, M.D. Zebin Zhu, M.D., Ph.D. Linhe Wang, M.D. Caihui Zhu, M.D. Yixi Zhang, M.D., Ph.D. Yunhua Tang, M.D., Ph.D. Chengjun Sun, M.D. Wei Xiong, M.D. Yuekun Shen, M.D., Ph.D. Xiaoxiang Chen, M.D. Jinghong Xu, M.D. Tielong Wang, M.D. Yi Ma, M.D., Ph.D. Anbin Hu, M.D., Ph.D. Yinghua Chen, M.D., Ph.D. Xiaofeng Zhu, M.D., Ph.D. Jian Rong, M.D., Ph.D. Changjie Cai, M.D., Ph.D. Fengqiu Gong, M.P.H. Xiangdong Guan, M.D., Ph.D. Wenqi Huang, M.D., Ph.D. Dicken Shiu-Chung Ko, M.D., Ph.D. Xianchang Li, M.D., Ph.D. Stefan G Tullius, M.D., Ph.D. Jiefu Huang, M.D., Ph.D. Weiqiang Ju, M.D., Ph.D. Xiaoshun He, M.D., Ph.D. |
author_sort |
Zhiyong Guo, M.D., Ph.D. |
title |
Ischaemia-free liver transplantation in humans: a first-in-human trial |
title_short |
Ischaemia-free liver transplantation in humans: a first-in-human trial |
title_full |
Ischaemia-free liver transplantation in humans: a first-in-human trial |
title_fullStr |
Ischaemia-free liver transplantation in humans: a first-in-human trial |
title_full_unstemmed |
Ischaemia-free liver transplantation in humans: a first-in-human trial |
title_sort |
ischaemia-free liver transplantation in humans: a first-in-human trial |
publisher |
Elsevier |
series |
The Lancet Regional Health. Western Pacific |
issn |
2666-6065 |
publishDate |
2021-11-01 |
description |
Summary: Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences.Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT).Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach.Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers.Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology.Panel: Research in context |
url |
http://www.sciencedirect.com/science/article/pii/S2666606521001693 |
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doaj-0d55f75fdf2c4f79ae6d5716985bf8c42021-08-28T04:48:54ZengElsevierThe Lancet Regional Health. Western Pacific2666-60652021-11-0116100260Ischaemia-free liver transplantation in humans: a first-in-human trialZhiyong Guo, M.D., Ph.D.0Qiang Zhao, M.D., Ph.D.1Shanzhou Huang, M.D., Ph.D.2Changjun Huang, M.D.3Dongping Wang, M.D., Ph.D.4Lu Yang, M.D., Ph.D.5Jian Zhang, M.Sc.6Maogen Chen, M.D., Ph.D.7Linwei Wu, M.D., Ph.D.8Zhiheng Zhang, M.D.9Zebin Zhu, M.D., Ph.D.10Linhe Wang, M.D.11Caihui Zhu, M.D.12Yixi Zhang, M.D., Ph.D.13Yunhua Tang, M.D., Ph.D.14Chengjun Sun, M.D.15Wei Xiong, M.D.16Yuekun Shen, M.D., Ph.D.17Xiaoxiang Chen, M.D.18Jinghong Xu, M.D.19Tielong Wang, M.D.20Yi Ma, M.D., Ph.D.21Anbin Hu, M.D., Ph.D.22Yinghua Chen, M.D., Ph.D.23Xiaofeng Zhu, M.D., Ph.D.24Jian Rong, M.D., Ph.D.25Changjie Cai, M.D., Ph.D.26Fengqiu Gong, M.P.H.27Xiangdong Guan, M.D., Ph.D.28Wenqi Huang, M.D., Ph.D.29Dicken Shiu-Chung Ko, M.D., Ph.D.30Xianchang Li, M.D., Ph.D.31Stefan G Tullius, M.D., Ph.D.32Jiefu Huang, M.D., Ph.D.33Weiqiang Ju, M.D., Ph.D.34Xiaoshun He, M.D., Ph.D.35Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, China; Corresponding authors at: Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, NO. 58 Zhongshan Er Road, Guangzhou 510080, China; Tel: 86-20-87306082; Fax: 86-20-87306082.Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaDepartment of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaDepartment of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, ChinaDepartment of Cardiopulmonary Bypass, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaSurgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaOperating Room and Anaesthesia Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaSurgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Surgery, Steward St. Elizabeth's Medical Centre, Tufts University School of Medicine, Boston, MA 02115, USAOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, China; Immunobiology and Transplant Science Centre, Houston Methodist Research Institute, Houston, Texas 77030, USADivision of Transplant Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Department of Surgery, Peking Union Medical College Hospital, Beijing 100032, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, China; Corresponding authors at: Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, NO. 58 Zhongshan Er Road, Guangzhou 510080, China; Tel: 86-20-87306082; Fax: 86-20-87306082.Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou 510080, China; Corresponding authors at: Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, NO. 58 Zhongshan Er Road, Guangzhou 510080, China; Tel: 86-20-87306082; Fax: 86-20-87306082.Summary: Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences.Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT).Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach.Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers.Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology.Panel: Research in contexthttp://www.sciencedirect.com/science/article/pii/S2666606521001693 |