Oxygenated Hypothermic Machine Perfusion After Static Cold Storage Improves Hepatobiliary Function of Extended Criteria Donor Livers

In Brief Background The mechanism through which oxygenated hypothermic machine perfusion (HMP) improves viability of human extended criteria donor (ECD) livers is not well known. Aim of this study was to examine the benefits of oxygenated HMP after static cold storage (SCS). Methods Eighteen ECD livers that were declined for transplantation underwent ex situ viability testing using normothermic (37°C) machine perfusion (NMP) after traditional SCS (0°C-4°C) for 7 to 9 hours. In the intervention group (n = 6), livers underwent 2 hours of oxygenated HMP (at 12°C) after SCS and before NMP. Twelve control livers underwent NMP without oxygenated HMP after SCS. Results During HMP, hepatic ATP content increased greater than 15-fold, and levels remained significantly higher during the first 4 hours of NMP in the HMP group, compared with controls. Cumulative bile production and biliary secretion of bilirubin and bicarbonate were significantly higher after HMP, compared with controls. In addition, the levels of lactate and glucose were less elevated after HMP compared with SCS preservation alone. In contrast, there were no differences in levels of hepatobiliary injury markers AST, ALT, LDH, and gamma-GT after 6 hours of NMP. Hepatic histology at baseline and after 6 hours of NMP revealed no differences in the amount of ischemic necrosis between both groups. Conclusions Two hours of oxygenated HMP after traditional SCS restores hepatic ATP levels and improves hepatobiliary function but does not reduce (preexisting) hepatobiliary injury in ECD livers. The authors present data in preserved human livers discarded for transplantation that oxygenated hypothermic machine perfusion restores cellular energy stores and preserves function when tested in an ex vivo system. Oxygenated end-ischemic perfusion may add a practical, new alternative to the growing field of organ restoration in deceased donor organ retrieval.