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

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

doi:10.1016/j.jhep.2023.04.010

Cited by 28 publications

(21 citation statements)

References 46 publications

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“…In addition, logistical reasons preventing immediate transplantation are also a reason for using the IFLT technique. Furthermore, based on the results of the randomized controlled trial, we have reason to believe that IFLT could significantly improve the outcomes and reduce complications such as biliary complications of patients undergone LT. 15 Additionally, IRI can also lead to late graft loss by contributing to ischemia-type biliary lesions (ITBL). 20 ITBL is the major reason for late graft loss in liver transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…14 In particular, in a recent randomized controlled trial, we demonstrated that IFLT significantly reduced complications related to IRI. 15 Therefore, here we share our experience on large animals of IFLT in pigs for investigating the protective mechanisms of IFLT in IRI, hepatocellular carcinoma recurrence, immune rejection, and the promotion and potential for application of IFLT at other centers.…”

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confidence: 95%

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Development of a Large Animal Model of Ischemia-free Liver Transplantation in Pigs

Tang,

Li,

Wang

et al. 2024

Transplantation Direct

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Background. In organ transplantation, ischemia, and reperfusion injury (IRI) is considered as an inevitable event and the major contributor to graft failure. Ischemia-free liver transplantation (IFLT) is a novel transplant procedure that can prevent IRI and provide better transplant outcomes. However, a large animal model of IFLT has not been reported. Therefore, we develop a new, reproducible, and stable model of IFLT in pigs for investigating mechanisms of IFLT in IRI. Methods. Ten pigs were subjected to IFLT or conventional liver transplantation (CLT). Donor livers in IFLT underwent 6-h continuous normothermic machine perfusion (NMP) throughout graft procurement, preservation, and implantation, whereas livers in CLT were subjected to 6-h cold storage before implantation. The early reperfusion injury was compared between the 2 groups. Results. Continuous bile production, low lactate, and liver enzyme levels were observed during NMP in IFLT. All animals survived after liver transplantation. The posttransplant graft function was improved with IFLT when compared with CLT. Minimal histologic changes, fewer apoptotic hepatocytes, less sinusoidal endothelial cell injury, and proinflammatory cytokine (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) release after graft revascularization were documented in the IFLT group versus the CLT group. Conclusions. We report that the concept of IFLT is achievable in pigs. This innovation provides a potential strategy to investigate the mechanisms of IRI and provide better transplant outcomes for clinical practice.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

Development of a Large Animal Model of Ischemia-free Liver Transplantation in Pigs

Tang,

Li,

Wang

et al. 2024

Transplantation Direct

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“…Guo et al performed an RCT to investigate whether ischemia-free liver transplantation (IFLT) under normothermic machine perfusion can reduce complications related to graft IRI compared to conventional LT (CLT) using static cold storage. 57 Sixty-five patients were included in the analysis: 32 received IFLT and 33 received CLT. EAD occurred in 2 recipients (6%) randomized to IFLT and in 8 (24%) randomized to CLT (P = .044).…”

Section: Organ Perfusionmentioning

confidence: 99%

Abdominal Organ Transplantation: Noteworthy Literature in 2023

Katayama,

Maffucci,

Domanski

et al. 2024

Semin Cardiothorac Vasc Anesth

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This review highlights noteworthy literature published in 2023 and pertinent to anesthesiologists and critical care physicians caring for patients undergoing abdominal organ transplantation. We feature 9 studies from 593 peer-reviewed papers on pancreatic transplantation, 3 from 194 on intestinal transplantation, and 28 from over 4513 on kidney transplantation. The liver transplantation section includes a special focus on 20 studies from 5666 clinical trial publications. We explore a broad range of topics, including donor management, perioperative recipient management, and innovative pharmacologic and mechanical interventions tested for the improvement of patient and graft outcomes and survival.

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“…Other strategies are also being employed to prevent IRI and reduce graft rejection rates. Guo et al 87 conducted a randomized controlled trial of the ischemia-free liver transplant technique, in which livers are procured and preserved without interruption of normothermic oxygenated blood supply, and subsequently implanted. Therefore, the role of IRI in both early and late graft dysfunction and rejection has been demonstrated.…”

Section: Main Factors Contributing To Irimentioning

confidence: 99%

Liver ischemia-reperfusion injury: From trigger loading to shot firing

Felli,

Muttillo

et al. 2023

Liver Transplantation

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An ischemia-reperfusion injury (IRI) results from a prolonged ischemic insult followed by the restoration of blood perfusion, being a common cause of morbidity and mortality, especially in liver transplantation. At the maximum of the potential damage, IRI is characterized by 2 main phases. The first is the ischemic phase, where the hypoxia and vascular stasis induces cell damage and the accumulation of damage-associated molecular patterns and cytokines. The second is the reperfusion phase, where the local sterile inflammatory response driven by innate immunity leads to a massive cell death and impaired liver functionality. The ischemic time becomes crucial in patients with underlying pathophysiological conditions. It is possible to compare this process to a shooting gun, where the loading trigger is the ischemia period and the firing shot is the reperfusion phase. In this optic, this article aims at reviewing the main ischemic events following the phases of the surgical timeline, considering the consequent reperfusion damage.

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

Cited by 28 publications

References 46 publications

Development of a Large Animal Model of Ischemia-free Liver Transplantation in Pigs

Development of a Large Animal Model of Ischemia-free Liver Transplantation in Pigs

Abdominal Organ Transplantation: Noteworthy Literature in 2023

Liver ischemia-reperfusion injury: From trigger loading to shot firing

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