Machine perfusion of liver grafts: hypothermic versus normothermic versus normothermic regional perfusion

Abstract

Machine perfusion (MP) techniques, including hypothermic oxygenated perfusion (HOPE), normothermic perfusion (NMP), and normothermic regional perfusion (NRP), have emerged as strategies to optimize outcomes of extended criteria donor (ECD) livers. Despite increasing adoption, clinical indications remain uncertain. To assist transplant professionals in clinical decision making, a systematic review and meta-analysis was conducted according to PRISMA guidelines, including randomized controlled trials (RCT) and cohort studies. Outcomes of interest were ischemic cholangiopathy (IC) and graft survival. Moderator analyses explored the influence of donor, recipient, and procedural factors. Studies comparing different MP techniques and sequential approached were also reviewed qualitatively. HOPE was associated with a significant reduction in IC (RR 0.50; CI 0.31, 0.79; P = 0.003) and improved graft survival (RR 1.08; CI 1.05, 1.08; P < 0.001), with evidence supported by RCT. NMP did not significantly influence IC or graft survival. Based on retrospective studies, NRP significantly improved IC (RR 0.1, CI 0.05, 0.21; P < 0.0001) and graft survival (RR 1.11; CI 1.05, 1.17; P = 0.0001) as compared to super-rapid recovery in controlled donation after circulatory death (DCD). Sequential approaches showed promise in high-risk grafts but require further validation. Studies comparing different MP approaches are still limited. Available literature is largely heterogeneous regarding risk profile and characteristic on included donors, study designs and considered endpoints, limiting the possibility to provide clear recommendation about clinical indications. Further comparative trials and studies focusing on specific donor-recipient scenarios are necessary to refine MP utilization and optimize LT outcomes.

Keywords: ischemic cholangiopathy; machine perfusion; machine perfusion indications; normothermic regional perfusion; sequential machine perfusion.

Figure 1.

Foster plots illustrating the effect of hypothermic oxygenated machine perfusion (HOPE) on the incidence of ischemic cholangiopathy and graft survival in liver transplantation.

Figure 2.

Foster plots illustrating the effect of normothermic machine perfusion (NMP) on the incidence of ischemic cholangiopathy and graft survival in liver transplantation.

Figure 3.

Foster plots illustrating the effect of normothermic regional perfusion (NRP) on the incidence of ischemic cholangiopathy and graft survival in liver transplantation.