The Use of Continuous Extended Criteria Graft Perfusion Will Lead to an Increase in Transplantable Organs

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Liver transplantation (LT) is one of the marvels of modern medicine. Over a period of 50 years, LT has gone from a procedure performed in desperate situations to one that is now almost routine. Along the way, we have developed a better understanding of liver failure physiology and made major advances in all aspects of patient care, including immunosuppression, surgical and anesthesia technique, and perioperative care. In the United States, over 7000 LT were performed in 2015. Before 2015, there was a noticeable decline in the rate of transplantation. The single most significant limitation to LT is the lack of available organs. Considering that almost 15 000 patients are currently on the waiting list, increasing the number of transplantable organs must be a priority.
To increase the number of transplantable organs, the use of discarded and extended criteria grafts (ECG), such as those obtained from donation after cardiac death (DCD), has increased. The number of discarded organs has been relatively stable for the last 15 years (8% to 11%, Organ Procurement and Transplantation Network data). Since the first DCD transplantation in 1993, the use of this type of graft has slowly increased in the United States, reaching 5.7 % in 2016 (OPTN data). The relatively low utilization of DCD organs is because of inferior outcomes in comparison to when donation after brain death (DBD) grafts are used.1 We must develop strategies to ensure these grafts are of the highest quality. Continuous graft perfusion before transplantation is one of these strategies.
In this issue, Compagnon et al2 evaluated the feasibility of using a transportable perfusion system (Airdrive) to preserve DCD liver grafts in pigs. The authors used a continuously oxygenated hypothermic pulsatile perfusion (HMP) system. This approach enables initiating graft perfusion early, subsequently shortening cold ischemia time (CIT).
Perfusing grafts to improve quality is not a new idea. Since the 1970s, HMP was used to preserve kidney grafts.3 Perfusion of the liver is much more challenging. Historically, 2 experimental perfusion paradigms were used, normothermic and hypothermic.
The advantages of normothermic preservation are that it maintains physiological conditions during preservation and has been shown to attenuate the risk of endothelial damage.4 Fondevila et al5 have demonstrated that normothermic perfusion for uncontrolled DCD human liver grafts is feasible. Patient and graft survivals were similar in comparison to a matched DBD group.
Currently, HMP is the most frequently used approach. It maintains the physiology of both endothelial cells and hepatocytes and has been shown to improve the condition of marginal grafts.6 This approach is also associated with preserved mitochondrial function and decreased release of reactive oxygen species.7 In a recent prospective evaluation, Guarrera et al8 demonstrated that patients who received an ECG, which was declined by United Network for Organ Sharing but preserved with continuous HMP, had superior outcomes in comparison to patients receiving ECGs preserved under static cold storage.
The study performed by Compagnon et al is an excellent example of a well-designed evaluation. In this prospective study, the authors chose a prolonged warm ischemia time of 60 minutes for both DCD groups and were able to demonstrate the superiority of HMP. For the control group, the authors used grafts from beating heart donors preserved under hypothermic conditions (4°C). Hemodynamic parameters after graft reperfusion in the DCD, nonperfusion group were significantly worse in comparison to those in the HMP group, as well as in controls. Animals receiving HMP, and controls, had significantly better survival than those in the DCD, nonperfusion group. After transplantation, the HMP group was associated with both decreased hepatocellular damage and sinusoidal dilatation, compared with nonperfused DCD grafts.
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