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Advances in machine perfusion technology have significantly improved organ utilization. However, consensus regarding the best dynamic preservation modality remains elusive. In this report, we evaluate recent results of clinical studies for different perfusion modalities and review new avenues of basic science aimed at organ rehabilitation. Randomized clinical trials of normothermic and hypothermic perfusion for liver preservation have demonstrated excellent patient and graft survival. Additional strategies that combine multiple preservation modalities show promise in maximizing utilization of severely injured grafts. Studies of machine perfusion with adjunct therapeutics for organ rehabilitation are being actively explored in the pre-clinical setting with potential for rapid translation into clinical trials. As machine perfusion becomes more widely incorporated into routine clinical use, graft utilization and transplant outcomes are likely to further improve. Logistics considerations that expand the use of this technology while minimizing costs will foster its broader adoption. Therapeutic strategies that aim to rehabilitate untransplantable grafts have the potential to greatly expand the pool of donor organs for transplantation, thereby easing the organ shortage.

A limited supply of donor livers has led many centers to use marginal liver allografts for transplantation with increasing frequency. These allografts are at increased risk for both primary non-function, early allograft dysfunction, and other recipient complications following transplantation. Machine perfusion preservation is an emerging technology that limits the ischemia-reperfusion injury sustained during allograft preservation and may lead to improved outcomes following liver transplantation. While several clinical series has shown a benefit of machine perfusion in both standard and extended criteria donors, no guidelines exist on how to assess the viability high-risk organs that might otherwise be turned down for transplantation. In this review, we highlight the current state of the art in allograft preservation using machine perfusion in liver transplantation. We explore the various methods available to assess allograft viability during machine perfusion. As the transplant community continues to push the boundaries and include allografts traditionally unfit for transplantation, it will be important to establish clear criteria to distinguish transplantable from non-transplantable allografts.

Purpose of the Review Machine perfusion (MP) is a novel technology recently introduced in liver transplantation, redefining the current practice of organ preservation and pushing the limits of high-risk liver utilisation. This review highlights the key benefits of machine perfusion over conventional static cold storage (SCS), demonstrated in human liver research and clinical transplants. Recent Findings The first clinical trials have demonstrated both safety and feasibility of MP. The most recent transplant series and result from a randomised trial suggest the technology is superior to SCS. The key benefits include extended period of organ preservation, decreased incidence of early allograft dysfunction and reduction of biliary complications. Normothermic liver perfusion allows viability testing to guide transplantability of the highest-risk organs. This technology also provides opportunities for therapeutic interventions to improve liver function and quality in organs that are currently declined for clinical use. Summary Machine perfusion is likely to transform the liver preservation pathway and to improve utilisation of high-risk grafts.

Hypothermic machine preservation (HMP) remains investigational in clinical liver transplantation. It is widely used, however, to preserve kidneys for transplantation because it has demonstrated improved results over static cold storage (CS). As with other machine preservations methods, HMP provides continuous circulation of nutrients and metabolic substrates during the ex-vivo period. Over the last few years, several groups worldwide have been actively translating HMP into the clinical arena for liver transplantation. In particular, HMP has been used for livers of varying quality, including those recovered from extended criteria donors (ECD) and donation after cardiac death (DCD) donors. Reports to date have focused on recipient hospital based HMP during the latter portion of the cold ischemic period. While some variability exists in technique, all clinical series to date have reported improved outcomes with reductions in early allograft dysfunction, biliary complications and reduced hospital length of stay. These benefits, together with the development of innovative portable HMP devices and further adoption by more centers worldwide, have “broken the ice” for more widespread use of HMP and subsequent expanded elucidation of its benefits.

The ongoing shortage of donor organs for liver transplantation results in high mortality rates for those on the waiting list. This has triggered considerable interest in the use of marginal liver grafts to increase the donor pool. Unfortunately, marginal grafts poorly tolerate preservation by cold storage (CS), resulting in an increased risk of liver injury and poor graft function after transplantation. Better preservation techniques are needed to fully utilize marginal grafts and to expand the number of organ donors. Animal studies have demonstrated normothermic ex vivo liver perfusion to be superior to conventional CS. Recently, the first clinical trial of normothermic ex vivo liver perfusion was completed with promising results. Similarly, in situ recirculation after cardiac arrest as the initial preservation method before organ procurement has proven to be a valuable technique to make more liver grafts available for transplantation. Though technically more complex and economically more expensive, normothermic liver perfusion is a promising and innovative technique that is able to positively impact current transplant practice and outcomes.

Liver transplantation is the primary treatment for end-stage liver disease, but demand exceeds supply due to the shortage of available healthy donor grafts. To increase the supply of useable grafts for transplantation, innovative and better preservation methods are needed to enable the use of livers from extended criteria donors. Normothermic machine perfusion (NMP) has been extensively studied in the laboratory and holds great potential for expanding the donor pool. This review summarizes the progress that has been made in NMP over the last two decades, with emphasis on the recent studies preparing the method for clinical trials.

Dynamic preservation strategies such as hypothermic machine perfusion are increasingly discussed to improve liver graft quality before transplantation. This review summarizes current knowledge of this perfusion technique for liver preservation. We discuss optimization of perfusion conditions and current strategies to assess graft quality during cold perfusion. Next, we provide an overview of possible pathways of protection from ischemia-reperfusion injury. Finally, we report on recent clinical applications of human hypothermic machine liver perfusion.