DCD liver transplantation has expanded worldwide but remains associated with an increased risk of complications. Sequential use of normothermic regional perfusion (NRP) followed by ex-situ machine perfusion (MP) is increasingly adopted but the choice of MP technique remains controversial. This randomized controlled trial compares outcomes of dual-hypothermic oxygenated perfusion (D-HOPE) versus normothermic machine perfusion (NMP) following NRP in DCD liver transplantation. After NRP, 50 grafts (44 controlled and 6 uncontrolled DCD) were randomized 1:1 to D-HOPE or NMP using concealed allocation with sequentially numbered sealed envelopes. Ex-situ perfusion was not performed for additional assessment. The primary endpoint was 1-year incidence of serious adverse events (SAE), including graft or patient loss and biliary or vascular complications. Secondary endpoint included other perioperative outcomes. We have also performed an exploratory analysis to identify predictive factors of graft loss and SAE. No case of primary non-function or vascular complication occurred. One-year graft and patient survival were both 88% in the D-HOPE group and 100% in the NMP group ( p =0.07). One-year SAE rate was similar (16%vs.20%, p =0.31). Biliary leakage and postoperative dialysis rate were comparable between the two groups (16%vs.0%, p =0.12). Blood pH variation, lactate and IL-6 levels during NRP, perfusate lactate trend, portal flow, IL-6, IL-10 and TNF levels during D-HOPE and perfusate pH variations and IL-10 levels during NMP were related to graft loss. Conclusions: When applied after NRP, D-HOPE and NMP provide comparable mid-term clinical outcomes in DCD liver transplantation. Differences in specific complications may require individualized selection of ex-situ MP. The limited sample size and number of events preclude definitive conclusions regarding differences in individual complications or the relative efficacy of either ex-situ perfusion strategy. The observed differences in specific complications and exploratory associations with perfusion parameters warrant evaluation in larger prospective studies.

Many advantages have been reported with the use of machine perfusion (MP) to rescue extended criteria donor (ECD) grafts, improving both short- and long-term post-liver transplantation (LT) outcomes. Acute kidney injury (AKI) is a common post-LT complication associated with these grafts and may compromise patient outcomes and increase LT-related costs. The aim of the study was to analyze the incidence of AKI in recipients of MP-treated grafts compared with those receiving conventionally cold-stored (SCS) grafts, both before and after a propensity score matching (PSM). From a prospectively maintained database, LT recipients of MP-treated grafts were compared with SCS grafts transplanted in the same study period (January 2022–May 2025). PSM was performed based on donor risk index (DRI), macrosteatosis (≥ or <30%), and recipient NaMELD score using a 3:1 (MP vs. SCS) ratio. Of the 177 consecutive LTs, 30 were performed with MP-treated grafts (MP group) and 147 using SCS (SCS group). The MP group displayed more marginal characteristics: older age (72 vs. 62 years, p = 0.02), higher proportion of DCD (10% vs. 0, p = 0.04), and higher frequency of moderate steatosis (macro ≥ 30%, 10% vs. 2.7%, p = 0.09). AKI rates were similar between groups (63% vs. 45.6%, p = 0.16), as was the distribution across AKI stages. After PSM, donor and recipient characteristics were balanced, and AKI rates remained similar between groups (58.6% vs. 47.1%, p = 0.39). Donor diabetes and recipient age were independent predictors of AKI in multivariate analysis (donor diabetes OR 3.29, 95% CI 1.347–8.030; recipient age: OR 1.06, 95% CI 1.015–1.097, both p < 0.05). MCP-1 and TNF-α levels measured in the perfusate fluid within the first minutes of perfusion were positively correlated with post-LT creatinine peak (MCP-1, p = 0.00023, R = 0.58; TNF-α, p = 0.0004, R = 0.57). In conclusion, machine perfusion remains a valuable strategy for rescuing ECD liver grafts. In the current era—characterized by increasing use of machine-perfused grafts and extended criteria donors—recipients demonstrate postoperative renal outcomes comparable to those receiving conventionally preserved grafts.