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In Italy, 20 minutes of continuous, flat-line electrocardiogram are required for declaration of death. In the setting of organ donation after cardiocirculatory death (DCD), prolonged warm ischemia time prompted introduction of abdominal normothermic regional perfusion (NRP) followed by post-procurement, ex-situ machine perfusion. This was a retrospective review of DCD liver transplantations performed at two centers using sequential NRP and ex-situ machine perfusion. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, 11 (32.4%) based on NRP parameters (n=1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n=9, 26.5%), or severe macroangiopathy at back table evaluation (N=1, 3.0%). Twenty grafts (58.8%) (12 uncontrolled DCD, 8 controlled DCD) were considered eligible for LT, procured and perfused ex-situ (9 normothermic and 11 dual hypothermic machine perfusion). Eighteen (52.9%; 11 uncontrolled) were eventually transplanted. Median (IQR) no-flow time was 32.5 (30-39) minutes, while median functional-warm ischemia time was 52.5 (47-74) minutes (controlled DCD) and median low-flow time 112 (105-129) minutes (uncontrolled DCD). There was no primary non-function, while post-reperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury in 5 (28%). After a median follow up of 15.1 (9.5-22.3) months, one case of ischemic-type biliary lesion and one patient death were reported. DCD liver transplantation is feasible even with the 20-minute no-touch rule. Strict normothermic regional perfusion and ex-situ machine perfusion selection criteria are needed to optimize post-operative results.

Ex situ normothermic machine perfusion (NMP) might minimize ischemia/reperfusion injury (IRI) of liver grafts. In this study, 20 primary liver transplantation recipients of older grafts (≥70 years) were randomized 1:1 to NMP or cold storage (CS) groups. The primary study endpoint was to evaluate graft and patient survival at 6 months posttransplantation. The secondary endpoint was to evaluate liver and bile duct biopsies; IRI by means of peak transaminases within 7 days after surgery; and incidence of biliary complications at month 6. Liver and bile duct biopsies were collected at bench surgery, end of ex situ NMP, and end of transplant surgery. Interleukin (IL) 6, IL10, and tumor necrosis factor α (TNF-α) perfusate concentrations were tested during NMP. All grafts were successfully transplanted. Median (interquartile range) posttransplant aspartate aminotransferase peak was 709 (371-1575) IU/L for NMP and 574 (377-1162) IU/L for CS (P = 0.597). There was 1 hepatic artery thrombosis in the NMP group and 1 death in the CS group. In NMP, we observed high TNF-α perfusate levels, and these were inversely correlated with lactate (P < 0.001). Electron microscopy showed decreased mitochondrial volume density and steatosis and an increased volume density of autophagic vacuoles at the end of transplantation in NMP versus CS patients (P < 0.001). Use of NMP with older liver grafts is associated with histological evidence of reduced IRI, although the clinical benefit remains to be demonstrated.