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

Abstract

•IFLT is a unique transplant procedure developed to avoid graft ischemia reperfusion injury.•This study represents the first randomized trial comparing IFLT and conventional liver transplantation.•IFLT can significantly reduce the incidence of almost all complications related to ischemia reperfusion injury. Background & AimsIschemia-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.MethodsIn 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.ResultsOut 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).ConclusionsAmong patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.Clinical trial registrationchictr.org. ChiCTR1900021158.Impact and implicationsIschemia-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. 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. 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. 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). Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.