Machine perfusion strategies in Liver Transplantation: A systematic review, pairwise, and network meta-analysis of randomized controlled trials

Background : Machine perfusion (MP), including hypothermic oxygenated machine perfusion (HOPE), dual HOPE, normothermic machine perfusion (NMP), NMP ischemia-free liver transplantation (NMP-ILT), and controlled oxygenated rewarming (COR), is increasingly being investigated to improve liver graft quality from extended criteria donors and donors after circulatory death and expand the donor pool. This network meta-analysis investigates the comparative efficacy and safety of various liver MP strategies versus traditional static cold storage (SCS). Methods: We searched PubMed, Scopus, Web of Science, and Cochrane Controlled Register of Trials for randomized controlled trials (RCTs) comparing liver transplantation (LT) outcomes between SCS and MP techniques. The primary outcome was the incidence of early allograft dysfunction (EAD). Secondary endpoints included 1-year graft survival, the incidence of graft failure/loss, post-reperfusion syndrome, biliary complications, the need for renal replacement therapy (RRT), graft-related patient mortality, and the length of intensive care unit (ICU) and hospital stay. R-software was used to conduct a network meta-analysis using a frequentist framework. PROSPERO ID: CRD42024549254. Results: We included 12 RCTs involving 1,628 patients undergoing LT (801 in the liver MP groups and 832 in the SCS group). Compared to SCS, HOPE/dHOPE, but not other MP strategies, was associated with a significantly lower risk of EAD (RR: 0.53, 95% CI [0.37, 0.74], p =0.0002), improved 1-year graft survival rate (RR: 1.07, 95% CI [1.01, 1.14], p =0.02), decreased graft failure/loss (RR: 0.38, 95% CI [0.16, 0.90], p =0.03), and reduced the risk of biliary complications (RR: 0.52, 95% CI [0.43, 0.75], p < 0.0001). Compared to SCS, NMP (RR: 0.49, 95% CI [0.24, 0.96] and NMP-ILT (RR: 0.15, 95% CI [0.04, 0.57], both significantly reduced the risk of post-perfusion syndrome. There is no difference between SCS and MP groups in the risk of RRT, graft-related patient mortality, and ICU and hospital stay length. Conclusion: Our meta-analysis showed that HOPE/dual-HOPE is a promising alternative to SCS for donor liver preservation. These new techniques can help expand the donor pool with similar or even better post-LT outcomes.