The role of machine perfusion in preventing recurrence after liver transplant for hepatocellular carcinoma: a systematic review and meta-analysis

Background: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT), but post-transplant recurrence remains a major cause of treatment failure. Ischemia-reperfusion injury (IRI) has been implicated in tumor recurrence through modulation of the hepatic microenvironment. Machine perfusion (MP) techniques reduce IRI and may improve oncologic outcomes. This systematic review and meta-analysis evaluated the impact of MP versus static cold storage (SCS) on HCC recurrence following LT. Methods: A systematic search of PubMed, CENTRAL, Scopus, Google Scholar and ClinicalTrials.gov was conducted from database inception to January 31, 2026. Studies comparing HCC recurrence after LT using MP or SCS graft preservation were included. The primary outcome was post-transplant HCC recurrence. Secondary outcomes included microvascular invasion (MVI), pre-transplant alpha-fetoprotein (AFP), Milan criteria status, and neoadjuvant therapies. Pooled odds ratios (ORs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using RevMan 5.4.1. Results: Ten studies involving 6,652 patients (4,944 SCS and 1,708 MP) were included. Nine studies evaluated hypothermic oxygenated perfusion and one assessed ischemia-free liver transplantation. Meta-analysis demonstrated a significantly higher risk of HCC recurrence in the SCS group compared with the MP group (OR 2.34, 95% CI 1.40–3.91; p = 0.001; I²=53%). Sensitivity analysis confirmed the robustness of the finding (OR 2.26, 95% CI 1.48–3.45; p = 0.0002; I²=22%). Subgroup analysis restricted to hypothermic oxygenated perfusion also favored MP (OR 1.97, 95% CI 1.25–3.10; p = 0.003). No significant differences were observed between groups regarding pre-transplant AFP levels (SMD 0.02, 95% CI − 0.09 to 0.13; p = 0.68), Milan criteria status (OR 0.83, 95% CI 0.59–1.19; p = 0.32), use of neoadjuvant therapies, or MVI. Conclusions: Machine perfusion for liver graft preservation is associated with a lower risk of HCC recurrence after liver transplantation compared with static cold storage. This benefit appears independent of baseline tumor characteristics and pre-transplant treatments. Given the predominance of retrospective studies, further prospective multicenter studies and randomized controlled trials are needed to confirm these findings and define the oncologic role of machine perfusion in liver transplantation for HCC.