A randomized controlled trial of normothermic versus dual-hypothermic oxygenated ex-situ perfusion in DCD liver transplantation

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.