Prolonged preservation of donor livers: the benefits of hypothermic machine perfusion

A major challenge in liver transplantation lies in the short time a donor liver can be kept viable outside the body. Preservation by traditional static cold storage is a simple and effective approach to preserve good quality donor livers, but is associated with a number of limitations, including inevitable ischemia-reperfusion injury and a limited preservation time. Machine perfusion as a novel method of organ preservation facilitates the preservation and optimization of donor organs at variable temperatures. It has been shown that a brief period (2 hours) of hypothermic (4-12°C) oxygenated machine perfusion (HOPE) protects livers against ischemia-reperfusion injury. In this thesis, we investigated whether HOPE could also be used to prolong preservation time. In a preclinical study, we show successful preservation of porcine donor livers up to 24 hours with equivalent hepatobiliary function and injury after reperfusion compared to livers preserved with 2 hours HOPE. The results of a multicenter, retrospective, cohort study show that outcomes after liver transplantation are not compromised when livers are preserved by prolonged (≥4 hours) HOPE with total preservation times up to 21 hours. Finally, a prospective clinical trial was initiated to investigate safety and feasibility of prolonged HOPE in liver transplantation (DHOPE-PRO trial). If the results of this trial confirm prolonged preservation of donor livers by HOPE is safe and feasible, this may have important implications for everyday transplant logistics.