The role of sequential normothermic regional perfusion and end-ischemic normothermic machine perfusion in liver transplantation from very extended uncontrolled donation after cardiocirculatory death

The use of pre-procurement normothermic regional perfusion (NRP) allowed us to implement controlled DCD liver transplantation with results comparable to brain death donors, but the use of uncontrolled DCD is declining due to logistic challenges and the high incidence of post-transplant complications. In Italy, the mandatory stand-off period of 20 min for DCD donors has driven the combined use of NRP and ex-situ machine perfusion with the intent to counterbalance the negative impact of prolonged warm ischemia. Organ viability during NRP is based on duration of warm ischemia, regional perfusion flow, lactate, transaminases values and histology, and those used in Italy are the widest worldwide. However, this evaluation can be difficult, especially when the acute damage is particularly severe. The use of ex-situ NRP could provide a safe organ evaluation. In the period from 06/2020 to 06/2022, all DCD grafts exceeding NRP viability criteria at a single center were eventually evaluated using ex-situ normothermic machine perfusion. Machine perfusion viability criteria were based on lactate clearance, irrespectively to bile production, unless 1-h transaminases perfusate level were not exceeding 5000 IU/L. Three cases of uncontrolled DCD grafts in excess of NRP viability criteria underwent ex-situ graft evaluation. Two matched ex-situ normothermic machine perfusion viability criteria and were successfully transplanted. Both recipients are doing well after 26 and 5 months after surgery with no signs of ischemic cholangiopathy. This experience suggests that the sequential use of NRP and normothermic machine perfusion may further expand the boundaries of organ viability in uncontrolled DCD liver transplantation.