Transplantation of extended criteria donor livers: Improving outcome with optimized donor selection and machine perfusion

Due to donor organ shortage, livers procured from suboptimal donors or so-called ‘extended criteria donors’ (ECD) are increasingly used for transplantation. Examples of ECD are older donors or donors deceased after circulatory death (DCD). Transplantation of ECD livers is associated with increased rate of complications such as non-anastomotic strictures (NAS) of the donor bile ducts. In this thesis we first investigated the outcome of several subtypes of ECD liver transplantation. We found that transplantation of pediatric DCD livers resulted in good long term outcome with low incidence of NAS. Moreover, we demonstrated that transplantation of suboptimal heart-beating (brain dead) donor livers was associated with high incidence and costs of biliary complications such as NAS, but not with worse survival or higher total costs. Secondly, we investigated the application of ex situ machine perfusion preservation. We demonstrated that DCD liver transplantation following end-ischemic dual hypothermic oxygenated machine perfusion (DHOPE) was feasible and safe, liver function was better and biliary injury was less. DHOPE was performed by connecting the liver to a machine and perfusing it with cold oxygenated fluid just before transplantation in the recipient. Subsequently, we initiated a prospective, multicenter, international, randomized, controlled clinical trial to study the efficiency of DHOPE in reducing the incidence of NAS after DCD liver transplantation. The study protocol is described in this thesis. Finally, we describe the development of the first organ preservation and resuscitation (OPR) unit which is designed to facilitate clinical grade machine perfusion of lungs, livers, and kidneys.