Abstract
Although efforts have been made by transplant centers to increase the pool of available livers by extending the criteria of liver acceptance, this practice creates risks for recipients that include primary non-function of the graft, early allograft dysfunction and post-operative complications. Donor liver machine perfusion (MP) is a promising novel strategy that not only decreases cold ischemia time, but also serves as a method of assessing the viability of the graft. In this review, we summarize the data from liver machine perfusion clinical trials and discuss the various techniques available to date as well as future applications of machine perfusion. A variety of approaches have been reported including hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP); the advantages and disadvantages of each are just now beginning to be resolved. Important in this effort is developing markers of viability with lactate being the most predictive of graft functionality. The advent of machine perfusion has also permitted completely ischemia free transplantation by utilization of in situ NMP showed promising results. Animal studies that focus on defatting steatotic livers via NMP as well as groups that work on regenerating liver tissue ex vivo via MP. The broad incorporation of machine perfusion into routine clinical practice seems incredible.
Highlights
Liver transplantation (LT) is the only curative treatment for patients with end-stage liver disease and select liver cancers
Fewer biliary complications, decreased hospitalization period in treatment group 11 times increase in adenosine triphosphate (ATP), lower LFTs, total bilirubin (TBili) at 30 days post-transplantation in treatment group Fewer biliary complications and less biliary histologic damage in treatment group Lower lactate and INR levels, less fresh frozen plasma (FFP), significantly higher rate of 5 year survival in treatment group DHOPE treated livers had a smaller increase in K+ levels and decreased needs in noradrenaline No statistically significant difference in patients survival at 3, 6, and 12 months post-transplantation between the three groups
Immunofluorescence labeling showed fewer CD68 expressing cells in the hypothermic machine perfusion (HMP) group, especially in the reperfusion phase, indicating an attenuated macrophage activation. These results reveal the impact of HMP on a cellular level in reducing the oxidative stress, hypothermic shock, and ischemia-reperfusion injury that liver allografts would otherwise suffer in SCS
Summary
Liver transplantation (LT) is the only curative treatment for patients with end-stage liver disease and select liver cancers. Significant advances over the last three decades in procurement, preservation, operative technique, and post-transplant immunosuppression have enabled liver transplantation to be an effective therapeutic option throughout the United States and much of the world. Despite these advances, mortality on the waiting list remains high due to an ever-increasing shortage of suitable donor organs [1]. Extended criteria donors (ECD), live donor liver transplant, expanded organ sharing, and a variety of organ preservation techniques have been introduced as means of increasing the pool of transplantable livers and decreasing waitlist mortality. We explore the opportunities provided by these innovative and enabling technologies by review of the clinical trials that have been conducted to date as well as the prospects for novel applications in the future
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