From Devices to Decisions: Strategic Integration of Complementary Perfusion Technologies

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The expanded adoption of advanced organ perfusion technologies has significantly increased the utilization of livers from donation after circulatory death (DCD) donors by enabling improved preservation, viability assessment, and mitigation of ischemia/reperfusion injury, thereby expanding the pool of transplantable organs previously considered high risk. The recent publication, “Sequential in situ normothermic regional perfusion and ex situ normothermic machine perfusion in controlled donation after circulatory death liver transplantation: a retrospective single-center experience,” details a real-world experience of a UK transplant program.1 The authors should be congratulated on their endeavor to expand the organ pool and provide details of their experience integrating perfusion technology in a complementary manner in DCD liver transplantation (LT). These data from a single center in the United Kingdom are unique in that they recount both clinical and logistical indications of livers undergoing normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP). Namely, the authors note that sequential perfusion technology was used secondary to donor reasons (n = 37; 53%) or instead to facilitate prolonged preservation for recipient reasons (n = 33; 47%). NRP was performed for 120 min and livers were declined pending liver appearance, if alanine transaminase (ALT) > 500 U/L or if ALT significantly rose between minute 60 and 120, or if lactate did not downtrend (>5 mmol/L). NMP via the OrganOx metra device (OrganOx, Oxford, United Kingdom) allowed back-to-base viability assessment via bile, ALT, and lactate assessments, and prolonged preservation if needed. Overall, a sequential approach allowed transplant of 52 of the 70 livers (74%) in the series that would otherwise have been discarded because of suboptimal NRP results or logistics. Interestingly, 65% of livers were able to be rescued when NMP was used after NRP for donor reasons. Failure to clear lactate during NRP was the most common reason for subsequent NMP use, and 19 of those 30 livers were transplanted after achieving reassuring NMP parameters. In the 15 cases (41%) that failed NRP ALT criteria, 9 were transplanted after NMP. One of these livers developed primary nonfunction and in retrospect had a 120-min NRP ALT of 1190 U/L and on NMP cleared lactate but had a 120-min ALT of 6055 U/L while not metabolizing glucose appropriately. There were 11 cases (30%) that failed both lactate and ALT on NRP, and 7 of those livers were transplanted after successful NMP. Recipient reasons for NRP-NMP included retransplant, extensive surgical history, awaiting biopsy results, simultaneous offers, bed availability, and late change in recipient; 5 livers were discarded following these scenarios due to nonreassuring NMP criteria. The data presented are encouraging; yet it should be noted that the viability assessment data are not adjusted, retrospective in nature, and the true fate of declined livers is unknown. Moreover, the viability parameters during NRP and NMP were not the same, as NMP also included assessment of biliary and glucose metabolism parameters. Although the authors recognize the limitations of lactate to guide acceptance during NRP, a nonreassuring lactate trend was the most common reason to pursue subsequent NMP. The authors challenged futility as about 20% of the cohort had a UK DCD risk score of higher than 10. However, despite opportunities to assess liver allografts with NRP and then NMP in a protocolized manner, there was still an unfortunate case of primary nonfunction and a nonanastomotic stricture rate of 6%. This nonanastomotic stricture rate may seem to have increased compared with other NRP and NMP studies; however, this rate is unadjusted and thus may not account for the high-risk donor-recipient pairs in the cohort. A comparison across clinical series is difficult, given small sample sizes and varying programmatic risk tolerance; nevertheless, these data facilitate important conversations for practice improvements. Although both NRP and NMP continue to be associated with increased utilization and improved outcomes in DCD LT, future research should aim to assess which viability criteria are optimal to guide acceptance. Importantly, markers that provide more sensitive and specific assessments of liver function are needed. The granularity of liver assessment on both NRP and NMP is a key strength of the article. Although derived from single-center data, these findings are likely generalizable across the United Kingdom, which follows standardized national protocols via the National Organ Retrieval Service.2 The United Kingdom provides 1 effective model for safeguarding quality in organ retrieval as the national system incorporates structured guidance on technical competencies, standardized organ passports for data capture, and routine debriefings to identify opportunities for continuous performance and process enhancements. Although the United Kingdom has had an established systematic approach for a decade, other countries, such as the United States, have only recently experienced a recent increase in NRP and NMP for DCD LT (Figure 1). Despite high volume and broad adoption, the US national data collection processes are still being redesigned to account for these novel technologies.FIGURE 1.: Deceased donor LT in the United States: UNOS Data 2017–2025. UNOS STAR files were queried from January 2017 to December 2025 for all adult primary deceased donor LTs and stratified by DBD and DCD. Multiorgan transplants were excluded. As a variable that does not exist in NRP was defined as DCD, with donor aortic cross clamp time to cold preservation perfusion time >40 min.3 NMP and HOPE were defined using the listed variables in the STAR files. The first FDA approval of an NMP device was in September 2021; HOPE data are captured in STAR files; however, a HOPE device is not approved in the United States as of 2025. A, Yearly increase in DCD LTs: UNOS Data 2017–2025. DCD LTs account for a larger percentage of total deceased donor LTs in the US each year from 2017 to 2025. B, Yearly increase in sequential NRP-NMP for DCD LT: UNOS Data 2017–2025. Different types of perfusion technology are accounting for a larger percentage of total deceased donor LTs in the United States each year from 2017 to 2025. Perfusion technologies used in the United States include NMP, NRP, and HOPE; the use of SCS alone for DCD LT is decreasing. DBD, donation after brain death; DCD, donation after circulatory death; FDA, Food and Drug Administration; HMP, hypothermic machine perfusion; HOPE, hypothermic oxygenated machine perfusion; LT, liver transplant; NMP, normothermic machine perfusion; NRP, normothermic regional perfusion; SCS, static cold storage; STAR, Standard Analysis And Research; UNOS, United Network for Organ Sharing.Similar to the collaborative spirit of the United Kingdom, transplant programs in the United States have formed the Consortium for Donation after Circulatory Death and Normothermic Regional Perfusion Outcomes Research and Development (CONCORD) to optimize consistency of data collection and bolster national efforts to assess outcomes. Groups such as CONCORD may be able to resolve unmet needs in US data collection—as has been done in the article by Gaurav et al—to help understand best practices for the strategic integration of perfusion technologies to achieve optimal patient outcomes. The US landscape is now recognizing sequential NRP followed by an ex situ perfusion technology as a viable approach.4 And, other technologies, such as hypothermic oxygenated machine perfusion (HOPE), may also address the needs of viability and prolonged preservation. For DCD LT, transplant teams must now establish strategies to address perfusion needs at the time of procurement at a donor hospital (NRP versus direct procurement); during transportation (automobile versus airplane); and at the recipient hosp

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