Machine Perfusion in Liver Transplantation: A Systematic Review and Meta-Analysis Comparing Outcomes with Conventional Static Cold Storage

Background: Static cold storage (SCS) remains the conventional standard for liver graft preservation; however, ischemia–reperfusion injury during storage may contribute to graft dysfunction, particularly with extended criteria and marginal donors. Machine perfusion (MP) has emerged as a promising alternative, yet existing systematic reviews are limited by their focus on individual perfusion modalities or selected donor populations. We performed a comprehensive systematic review and meta-analysis with pre-specified modality-specific subgroup analyses comparing all MP strategies with SCS in adult liver transplantation. Methods: This study was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420261355605). MEDLINE, Embase, and PubMed were systematically searched for comparative studies published between 2015 and 2025. Primary outcomes were early allograft dysfunction (EAD), primary non-function (PNF), and 1-year graft survival. Secondary outcomes included biliary complications, hepatic artery thrombosis (HAT), and postoperative transaminase levels. Pre-specified subgroup analyses were performed according to perfusion modality (NMP versus HMP/HOPE). Results: A total of 1448 records were identified. After removal of 309 duplicates and screening, 21 studies comprising 3665 patients were included. Compared with SCS, MP was associated with a significantly lower risk of EAD (RR 0.67, 95% CI 0.48–0.94; p = 0.020), PNF (RR 0.31, 95% CI 0.11–0.84; p = 0.020), and graft loss at one year (RR 0.54, 95% CI 0.36–0.81; p = 0.003; I² = 0%). Subgroup analysis demonstrated that reductions in EAD and PNF were driven by HMP/HOPE strategies (EAD: RR 0.66, 95% CI 0.45–0.98; PNF: RR 0.23, 95% CI 0.07–0.79), whereas NMP did not achieve statistical significance for these endpoints. No significant differences were observed in biliary complications or HAT. Conclusions: Machine perfusion is associated with improved early graft function, reduced primary non-function, and superior 1-year graft survival compared with static cold storage. The benefit for early graft outcomes is driven by hypothermic strategies. These findings provide modality-specific evidence to guide preservation strategy selection in clinical practice.