Hemostatic system activation and reperfusion injury in liver machine preservation and transplantation of extended criteria donor livers

For patients with end-stage liver disease and certain types of hepatic malignancies, liver transplantation is universally accepted as the most effective and only curable treatment available. The success of liver transplantation has ironically however, become one of the greatest challenges faced by transplant health professionals worldwide as a great discrepancy continues to exist between the supply of suitable donor livers for transplantation and the demand. In an effort to tackle the donor organ scarcity, a significant proportion of additional donor organs has resulted from the increased reliance on the use of extended criteria donor (ECD) livers. Such livers include; livers from older donors, livers that exceed the traditionally accepted degree of steatosis (or in lay terms; “fatty livers”) and livers donated after circulatory death (DCD). In fact, in 2018 in the Netherlands, more than 50% of deceased donor liver transplants were derived from DCD donors. Several studies have shown that selective use of ECD livers results in successful transplantation procedures and acceptable survival rates following transplantation. Nevertheless, a higher incidence of post-transplant morbidity such as early allograft dysfunction, (severe) intraoperative bleeding and life threatening biliary complications, have been reported after transplantations with ECD livers. Studies have shown that these are largely attributed to by ischemia-reperfusion injury (IR injury) incurred by these organs during the procurement, preservation and implantation processes. Machine perfusion (MP) is a promising alternative preservation modality that allows for the storage of donor organs under conditions simulating in vivo physiology. Therefore, ischemia, and subsequently, ischemia-reperfusion injury is minimized.
In this thesis more insight is provided into (1) the incidence of bleeding and coagulation problems in DCD transplantation, (2) machine perfusion as a method to (better) preserve ECD-DCD donor livers to reduce intra- and postoperative complications and (3) the effect of machine perfusion on the coagulation system and on ischemia-reperfusion damage in ECD-DCD donor livers.