A Review of Machine Perfusion Strategies in Liver Transplantation

Abstract

The acceptance of liver transplantation as the standard of care for end-stage liver diseases has led to a critical shortage of donor allografts. To expand the donor organ pool, many countries have liberalized the donor criteria including extended criteria donors and donation after circulatory death. These marginal livers are at a higher risk of injury when they are preserved using the standard static cold storage (SCS) preservation techniques. In recent years, research has focused on optimizing organ preservation techniques to protect these marginal livers. Machine perfusion (MP) of the expanded donor liver has witnessed considerable advancements in the last decade. Research has showed MP strategies to confer significant advantages over the SCS techniques, such as longer preservation times, viability assessment and the potential to recondition high risk allografts prior to implantation. In this review article, we address the topic of MP in liver allograft preservation, with emphasis on current trends in clinical application. We discuss the relevant clinical trials related to the techniques of hypothermic MP, normothermic MP, hypothermic oxygenated MP, and controlled oxygenated rewarming. We also discuss the potential applications of ex vivo therapeutics which may be relevant in the future to further optimize the allograft prior to transplantation.

Keywords: ALP, Alkaline phosphatase; ALT, Alanine transaminase; ASO, Antisense oligonucleotides; AST, Aspartate transaminase; CIT, Cold ischemia times; COPE, Consortium for Organ Preservation in Europe; COR, Controlled oxygenated rewarming; DBD, Donation after brain death; DCD, Donation after circulatory death; DHOPE, dual hypothermic oxygenated machine perfusion; EAD, Early allograft dysfunction; ECD, Extended criteria donors; ETC, Electron transport chain; GGT, Gamma glutamyl transferase; HCV, Hepatitis C virus; HMP, Hypothermic machine perfusion; HOPE, Hypothermic oxygenated machine perfusion; ICU, Intensive care unit; IGL, Institute George Lopez-1; INR, International normalized ratio; IRI, ischemia reperfusion injury; LDH, Lactate dehydrogenase; MELD, Model for end-stage liver disease; MP, Machine perfusion; NAS, Non-anastomotic biliary strictures; NMP, Normothermic machine perfusion; NO, Nitric oxide; PNF, Primary nonfunction; ROS, Reactive oxygen species; RT-PCR, Reverse transcription polymerase chain reaction; SNMP, Sub-normothermic machine perfusion; UW, University of Wisconsin; WIT, Warm ischemia times; hypothermic machine perfusion; hypothermic oxygenated machine perfusion; machine perfusion; normothermic machine perfusion; static cold storage.