Normothermic extracorporeal perfusion of porcine and human liver following donation after cardiac death

Michael A. Fink^1,4, Rinaldo Bellomo², Bruno Marino³, Graham Starkey⁴, Bao-Zhong Wang⁴, Nan Zhu⁴, Satoshi Suzuki², Shane Houston², Glenn Eastwood², Paolo Calzavacca², Neil Glassford, Brenton Chambers⁵, Alison Skene⁶, Antoine G. Schneider², Daryl Jones², Andrew Hilton², Helen Opdam⁷, Stephen Warrillow², Nicole Gauthier⁷, Lynne Johnson⁸, Robert M. Jones⁴

¹Department of Surgery, Austin Hospital, The University of Melbourne, Melbourne, Australia, ²Department of Intensive Care, Austin Hospital, Melbourne, Australia, ³Perfusion Services, Austin Hospital, Melbourne, Australia, ⁴Liver Transplant Unit, Austin Hospital, Melbourne, Australia, ⁵Faculty of Veterinary Science, The University of Melbourne, Melbourne, Australia, ⁶Department of Anatomical Pathology, Austin Hospital, Melbourne, Australia, ⁷DonateLife Victoria, Melbourne, Australia, ⁸Department of Radiology, Austin Hospital, Melbourne, Australia

Donation after cardiac death (DCD) has increased the pool of potential donors for liver transplantation.  However, DCD livers are at increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to protect, evaluate and transplant DCD livers.  Proof-of-concept experiments using a DCD model in the pig and in a discarded DCD human liver were performed to assess the short-term (3 - 4 hours) feasibility, histological effects and functional efficacy of NELP. Using extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion, and physiological perfusion pressures, we achieved NELP and evidence of function (bile production, paracetamol removal, maintenance of normal ammonia and lactate levels) for 4 hours in the pig livers subjected to 15 and 30 minutes of cardiac arrest before explantation and for 3 hours in the human liver.  There was essentially normal liver and biliary tract histology after 8 hours perfusion.  Our experiments justify further investigations of the feasibility and efficacy of human DCD liver preservation by ex-vivo perfusion.