A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease

Zhiyong Guo; Qiang Zhao; Zehua Jia; Changjun Huang; Dongping Wang; Weiqiang Ju; Jian Zhang; Lu Yang; Shanzhou Huang; Maogen Chen; Xiaofeng Zhu; Anbin Hu; Yi Ma; Linwei Wu; Yinghua Chen; Ming Han; Yunhua Tang; Guodong Wang; Linhe Wang; Lifen Li; Wei Xiong; Zhiheng Zhang; Yuekun Shen; Zhaoxia Tang; Caihui Zhu; Xiaoxiang Chen; Xiaoguang Hu; Yiwen Guo; Honghui Chen; Yihao Ma; Tao Zhang; Shunwei Huang; Ping Zeng; Simei Lai; Tielong Wang; Zhitao Chen; Jinlong Gong; Jia Yu; Canhui Sun; Chang Li; Haiyi Tan; Yao Liu; Yuqi Dong; Chengjun Sun; Bing Liao; Jun Ren; Zhenhai Zhou; Schlegel Andrea; Nashan Björn; Changjie Cai; Fengqiu Gong; Jian Rong; Wenqi Huang; Xiangdong Guan; Pierre Alain Clavien; Tullius G. Stefan; Jiefu Huang; Xiaoshun He

doi:10.1016/j.jhep.2023.04.010

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease

Zhiyong Guo, Qiang Zhao, Zehua Jia, Changjun Huang, Dongping Wang, Weiqiang Ju, Jian Zhang, Lu Yang, Shanzhou Huang, Maogen Chen, Xiaofeng Zhu, Anbin Hu, Yi Ma, Linwei Wu, Yinghua Chen, Ming Han, Yunhua Tang, Guodong Wang, Linhe Wang, Lifen LiWei Xiong, Zhiheng Zhang, Yuekun Shen, Zhaoxia Tang, Caihui Zhu, Xiaoxiang Chen, Xiaoguang Hu, Yiwen Guo, Honghui Chen, Yihao Ma, Tao Zhang, Shunwei Huang, Ping Zeng, Simei Lai, Tielong Wang, Zhitao Chen, Jinlong Gong, Jia Yu, Canhui Sun, Chang Li, Haiyi Tan, Yao Liu, Yuqi Dong, Chengjun Sun, Bing Liao, Jun Ren, Zhenhai Zhou, Schlegel Andrea, Nashan Björn, Changjie Cai, Fengqiu Gong, Jian Rong, Wenqi Huang, Xiangdong Guan, Pierre Alain Clavien, Tullius G. Stefan, Jiefu Huang, Xiaoshun He

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes.

METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI.

RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025).

CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.

CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158.

IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Original language	English (US)
Pages (from-to)	394-402
Number of pages	9
Journal	Journal of Hepatology
Volume	79
Issue number	2
DOIs	https://doi.org/10.1016/j.jhep.2023.04.010
State	Published - Aug 2023

Keywords

Early allograft dysfunction
End stage liver diseases
Ischemia reperfusion injury
Ischemia-free organ transplantation
Liver transplantation
Normothermic machine perfusion
Ischemia/pathology
Humans
End Stage Liver Disease/complications
Reperfusion Injury/etiology
Liver/pathology
Organ Preservation/methods
Perfusion/methods
Liver Transplantation/adverse effects

ASJC Scopus subject areas

Hepatology

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10.1016/j.jhep.2023.04.010

Cite this

Guo, Z., Zhao, Q., Jia, Z., Huang, C., Wang, D., Ju, W., Zhang, J., Yang, L., Huang, S., Chen, M., Zhu, X., Hu, A., Ma, Y., Wu, L., Chen, Y., Han, M., Tang, Y., Wang, G., Wang, L., ... He, X. (2023). A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease. Journal of Hepatology, 79(2), 394-402. https://doi.org/10.1016/j.jhep.2023.04.010

Guo, Z, Zhao, Q, Jia, Z, Huang, C, Wang, D, Ju, W, Zhang, J, Yang, L, Huang, S, Chen, M, Zhu, X, Hu, A, Ma, Y, Wu, L, Chen, Y, Han, M, Tang, Y, Wang, G, Wang, L, Li, L, Xiong, W, Zhang, Z, Shen, Y, Tang, Z, Zhu, C, Chen, X, Hu, X, Guo, Y, Chen, H, Ma, Y, Zhang, T, Huang, S, Zeng, P, Lai, S, Wang, T, Chen, Z, Gong, J, Yu, J, Sun, C, Li, C, Tan, H, Liu, Y, Dong, Y, Sun, C, Liao, B, Ren, J, Zhou, Z, Andrea, S, Björn, N, Cai, C, Gong, F, Rong, J, Huang, W, Guan, X, Clavien, PA, Stefan, TG, Huang, J & He, X 2023, 'A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease', Journal of Hepatology, vol. 79, no. 2, pp. 394-402. https://doi.org/10.1016/j.jhep.2023.04.010

@article{6e472e91b9be48c59c01aa26f0a6d795,

title = "A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease",

abstract = "BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes.METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI.RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025).CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158.IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.",

keywords = "Early allograft dysfunction, End stage liver diseases, Ischemia reperfusion injury, Ischemia-free organ transplantation, Liver transplantation, Normothermic machine perfusion, Ischemia/pathology, Humans, End Stage Liver Disease/complications, Reperfusion Injury/etiology, Liver/pathology, Organ Preservation/methods, Perfusion/methods, Liver Transplantation/adverse effects",

author = "Zhiyong Guo and Qiang Zhao and Zehua Jia and Changjun Huang and Dongping Wang and Weiqiang Ju and Jian Zhang and Lu Yang and Shanzhou Huang and Maogen Chen and Xiaofeng Zhu and Anbin Hu and Yi Ma and Linwei Wu and Yinghua Chen and Ming Han and Yunhua Tang and Guodong Wang and Linhe Wang and Lifen Li and Wei Xiong and Zhiheng Zhang and Yuekun Shen and Zhaoxia Tang and Caihui Zhu and Xiaoxiang Chen and Xiaoguang Hu and Yiwen Guo and Honghui Chen and Yihao Ma and Tao Zhang and Shunwei Huang and Ping Zeng and Simei Lai and Tielong Wang and Zhitao Chen and Jinlong Gong and Jia Yu and Canhui Sun and Chang Li and Haiyi Tan and Yao Liu and Yuqi Dong and Chengjun Sun and Bing Liao and Jun Ren and Zhenhai Zhou and Schlegel Andrea and Nashan Bj{\"o}rn and Changjie Cai and Fengqiu Gong and Jian Rong and Wenqi Huang and Xiangdong Guan and Clavien, {Pierre Alain} and Stefan, {Tullius G.} and Jiefu Huang and Xiaoshun He",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

doi = "10.1016/j.jhep.2023.04.010",

language = "English (US)",

volume = "79",

pages = "394--402",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "Elsevier",

number = "2",

}

TY - JOUR

T1 - A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease

AU - Guo, Zhiyong

AU - Zhao, Qiang

AU - Jia, Zehua

AU - Huang, Changjun

AU - Wang, Dongping

AU - Ju, Weiqiang

AU - Zhang, Jian

AU - Yang, Lu

AU - Huang, Shanzhou

AU - Chen, Maogen

AU - Zhu, Xiaofeng

AU - Hu, Anbin

AU - Ma, Yi

AU - Wu, Linwei

AU - Chen, Yinghua

AU - Han, Ming

AU - Tang, Yunhua

AU - Wang, Guodong

AU - Wang, Linhe

AU - Li, Lifen

AU - Xiong, Wei

AU - Zhang, Zhiheng

AU - Shen, Yuekun

AU - Tang, Zhaoxia

AU - Zhu, Caihui

AU - Chen, Xiaoxiang

AU - Hu, Xiaoguang

AU - Guo, Yiwen

AU - Chen, Honghui

AU - Ma, Yihao

AU - Zhang, Tao

AU - Huang, Shunwei

AU - Zeng, Ping

AU - Lai, Simei

AU - Wang, Tielong

AU - Chen, Zhitao

AU - Gong, Jinlong

AU - Yu, Jia

AU - Sun, Canhui

AU - Li, Chang

AU - Tan, Haiyi

AU - Liu, Yao

AU - Dong, Yuqi

AU - Sun, Chengjun

AU - Liao, Bing

AU - Ren, Jun

AU - Zhou, Zhenhai

AU - Andrea, Schlegel

AU - Björn, Nashan

AU - Cai, Changjie

AU - Gong, Fengqiu

AU - Rong, Jian

AU - Huang, Wenqi

AU - Guan, Xiangdong

AU - Clavien, Pierre Alain

AU - Stefan, Tullius G.

AU - Huang, Jiefu

AU - He, Xiaoshun

PY - 2023/8

Y1 - 2023/8

N2 - BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes.METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI.RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025).CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158.IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

AB - BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes.METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI.RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025).CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158.IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

KW - Early allograft dysfunction

KW - End stage liver diseases

KW - Ischemia reperfusion injury

KW - Ischemia-free organ transplantation

KW - Liver transplantation

KW - Normothermic machine perfusion

KW - Ischemia/pathology

KW - Humans

KW - End Stage Liver Disease/complications

KW - Reperfusion Injury/etiology

KW - Liver/pathology

KW - Organ Preservation/methods

KW - Perfusion/methods

KW - Liver Transplantation/adverse effects

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UR - http://www.scopus.com/inward/citedby.url?scp=85159281384&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2023.04.010

DO - 10.1016/j.jhep.2023.04.010

M3 - Article

C2 - 37086919

AN - SCOPUS:85159281384

SN - 0168-8278

VL - 79

SP - 394

EP - 402

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 2

ER -

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease

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