Machine perfusion of human donor livers with a focus on the biliary tree

Machine perfusion of human donor livers offers the possibility to protect organs against damage and to select more carefully. The results of normothermic machine perfusion (NMP) based on human blood were presented. Subsequently, an NMP perfusion fluid was developed that circumvented the use of human blood products and was based on bovine hemoglobin (HBOC-201). HBOC-perfused livers showed better function than livers perfused with human blood products. HBOC-201 can also be used as an oxygen carrier at lower temperatures, allowing cold rescuscitation followed by gradual rewarming to NMP. This protocol was tested in seven livers that were initially rejected for transplantation, five of which were successfully transplanted. Subsequently, it was demonstrated that bicarbonate, pH, and glucose in bile are accurate predictors of histological biliary injury during NMP, which is important because biliary injury is correlated to biliary strictures prior to transplantation. Liver and bile duct-derived micro-RNAs in perfusate and bile were also tested. Early release of these micro-RNAs were able to predict late function and damage during NMP. Furthermore, the ability of various preservation fluids to protect against biliary injury was investigated. HTK solution led to higher biliary injury compared to UW solution, which has important clinical implications since HTK solution is used widely and livers with a high risk of biliary complications are increasingly being transplanted. Finally, the so-called ex vivo “precision-cut bile duct slices” model was developed to study human bile ducts, bypassing the use of laboratory animals. This was the first study to show that cells in peribiliary glands – niches of stem cells in the bile duct wall that play a crucial role in the development of biliary strictures - respond with proliferation, migration and differentiation to restore biliary epithelium after biliary damage.