'Back-to-base' combined hypothermic and normothermic machine perfusion of human donor livers

Abstract

The shortage of suitable donor organs has resulted in the use of suboptimal, high-risk, extended-criteria donor (ECD) livers, which are at an increased risk of failure after transplantation. Compared with traditional static cold storage, dynamic preservation by ex situ machine perfusion reduces the risks associated with the transplantation of ECD organs. Ex situ machine perfusion strategies differ in timing (that is, speed of procurement and transport), perfusion duration and perfusion temperature. For 'back-to-base' protocols, the donor liver is statically cold stored during transportation to the recipient hospital (the 'base') and then perfused, instead of transporting the liver using a portable perfusion system. While dual hypothermic (8-12 °C) oxygenated machine perfusion (DHOPE) allows safe prolongation of preservation duration and reduces ischemia-reperfusion injury-related complications, including post-transplant cholangiopathy, normothermic machine perfusion (NMP) at 35-37 °C facilitates ex situ viability testing of both liver parenchyma and bile ducts. Here, we describe a clinical protocol for 'back-to-base' combined DHOPE and NMP, linked by a period of controlled oxygenated rewarming (COR), which we call the DHOPE-COR-NMP protocol. This protocol enables restoration of mitochondrial function after static ischemic preservation and minimizes both ischemia-reperfusion and temperature-shift-induced injury during the start of NMP. The NMP phase allows viability assessment before final donor liver acceptance for transplantation. Sequential DHOPE and COR-NMP may reduce the risks associated with transplantation of ECD livers and facilitate enhanced utilization, thereby helping to alleviate the organ shortage.