Return of the cold: How hypothermic oxygenated machine perfusion is changing liver transplantation

Hypothermic Oxygenated machine PErfusion (HOPE) has recently emerged as a preservation technique which can reduce ischemic injury and improve clinical outcomes following liver transplantation. First developed with the advent solid organ transplantation techniques, hypothermic machine perfusion largely fell out of favour following the development of preservation solutions which can satisfactorily preserve grafts using the cheap and simple method, static cold storage (SCS). However, with an increasing need to develop techniques to reduce graft injury and better utilise marginal and donation after circulatory death (DCD) grafts, HOPE has emerged as a relatively simple and safe technique to optimise clinical outcomes following liver transplantation. Perfusing the graft with cold, acellular, oxygenated perfusate either via the portal vein (PV) alone, or via both the PV and hepatic artery (HA), HOPE is generally commenced for a period of 1-2 h immediately prior to implantation. The technique has been validated by multiple randomised control trials, and pre-clinical evidence suggests HOPE primarily reduces graft injury by decreasing the accumulation of harmful mitochondrial intermediates, and subsequently, the severity of post-reperfusion injury. HOPE can also facilitate real time graft assessment, most notably via the measurement of flavin mononucleotide (FMN) in the perfusate, allowing transplant teams to make better informed clinical decisions prior to transplantation. HOPE may also provide a platform to administer novel therapeutic agents to ex situ organs without risk of systemic side effects. As such, HOPE is uniquely positioned to revolutionise how liver transplantation is approached and facilitate optimised clinical outcomes for liver transplant recipients.