Ex vivo machine perfusion: current applications and future directions in liver transplantation

Abstract

Background Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool. Purpose To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions. Methods A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. Results Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs. Conclusion Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.

Potential options to expand the intestinal donor pool: a comprehensive review

“…Lung and heart machine perfusion are also increasingly performed preclinically and clinically [36]. Machine perfusion is currently used to better asses the quality and function of extended-criteria donor organs and/or to safely prolong preservation time (long-distance transportation, combined organ transplantation and so on) [36,37 ▪ ,38]. However, machine perfusion is an unfinished product, and many parameters still need to be studied.…”

Comprehensive Approach to Assessment of Liver Viability During Normothermic Machine Perfusion

“…23 Transplant teams routinely inspect donor livers and make their decision about transplantation accordingly. 24 Surgeons evaluate the organ primarily based on appearance 3 and further activation of Kupffer cells and infiltration of leukocytes. 5 Activation of Kupffer cells and leukocytes worsen injury with further release of inflammatory cytokines.…”

“…2 Importantly, liver preservation using static cold storage does not allow immediate assessment of liver viability, which is essential for extended criteria donor (ECD) livers. Fortunately, there has been a recent resurgence of interest in normothermic machine perfusion (NMP), 3 which can provide nutrients and oxygen to the liver in a physiological state, minimize organ injury, and limit the damage caused by cold and warm ischemia (Figs. 1, 2).…”

The Need to Update Endpoints and Outcome Analysis in the Rapidly Changing Field of Liver Transplantation

“…23 bc have therefore gained importance as endpoint in clinical trials using DCD livers. 24 The clinical introduction of normothermic regional perfusion 25,26 for controlled and uncontrolled DCD donors (Maastricht II) in the 2000s, [27][28][29][30][31][32] followed by hypothermic machine perfusion in 2010, hypothermic oxygenated machine perfusion (HOPE) in 2014, controlled oxygenated rewarming and normothermic machine perfusion (NMP) in 2016, to ischemia-free organ transplantation in 2018 has advanced the ability to better preserve organs before, during and after retrieval 33 (Figure 2). As a result, more advanced scoring systems adopting a refined grading of the injury were developed.…”