Normothermic liver perfusion: Is the juice worth the squeeze?

“I lived every day of my clinical career with the horrible reality that more than half the people awaiting organs will never get them. We all long for the day when that is no longer true.”—Author Note, Last Night in the OR, Byers W. Shaw, Jr., MD The promise of normothermic machine perfusion (NMP) to transform liver transplantation is undeniable, but its journey remains fraught with technical and financial challenges. In their effort to debunk the transformative potential of NMP and its economics, Gao et al1 present their institutional experience with NMP using the TransMedics OCS system, delivering both compelling outcomes and questions that demand further scrutiny. The authors report on increased organ utilization from deceased donors, a shift toward more daytime operations, and shorter ICU and hospital stays, juxtaposed against significantly higher index hospitalization costs (+$47,666) and total organ acquisition costs (+$85,000; largely driven by the TransMedics “service package” costs) with NMP use. We commend their work for sparking dialogue on whether the logistical and clinical benefits of adopting an NMP program are money worth spending. However, as presented, this study falls short of clearly associating NMP with many of its claimed outcomes. With over 35% of DCD livers undergoing machine perfusion (MP) in 2023 and NMP as the predominant MP technique currently in the United States,2 the transplant community—ever vigilant in allocating scarce resources—will undoubtedly scrutinize these claims through the lens of equity and efficacy. The study highlights a substantial rise in the use of donation after circulatory death (DCD) grafts—from 5 in 2021 to 43 in 2023. While this increase partly reflects the growing use of NMP, the broader context complicates this narrative. According to OPTN data, the authors’ center performed 139 transplants in 2019, predominantly from donation after brain death (DBD) donors (133 DBD and 6 DCD). In the years following, transplant volumes declined during the COVID-19 pandemic—102 in 2020 (91 DBD and 11 DCD), 113 in 2021 (108 DBD and 5 DCD), and 117 in 2022 (100 DBD and 17 DCD). Although total transplants rebounded to 158 in 2023 (108 DBD and 50 DCD) and 156 in 2024 (90 DBD and 66 DCD), DBD transplants never recovered to their pre-pandemic level (133 in 2019). Multiple factors—COVID-19, institutional constraints, and the 2020 “acuity circles” liver allocation policy—likely spurred this shift in donor usage. In a recent study examining the effects of the allocation policy change on donor use, Chan et al3 categorized donor livers as “ideal” (I), “standard” (S), or “non-ideal” (NI). After the policy change, high MELD (HM; >28) centers—like the authors’ institution (Duke University)—saw increased annual transplants per center from I (10.6 before vs. 12.5 after, p<0.0082) and S (25.7 vs. 29.7, p=0.0003) donors, with no significant change in NI (32.6 vs. 34.3, p=0.2) or DCD (3.9 vs. 4.3, p=0.3) donors. Meanwhile, organ offer acceptance ratios declined (1.2 vs. 1.0, p=0.0003). Put simply, even though HM centers capitalized on an influx of higher-quality (I and S) donor livers and increased transplant volume, their DCD donor use remained static and organ offer acceptance ratios dropped. This pattern is evident in the authors’ center-specific OPTN data before and after the policy shift (February 2020). More to the point, as transplant volume at the authors’ center rebounded in 2023, the median listing MELD score dropped to 24 in the NMP group while it remained 29 in the static cold storage (SCS) group (p<0.001), suggesting that NMP may facilitate graft use in recipients with more stable liver disease. Nonetheless, it remains unclear whether DBD volume truly stabilized or was offset by increased DCD utilization. If the latter, NMP might be shifting graft usage specifically at the authors’ center—even while expanding the donor pool nationally—directing potentially lower-quality DCD livers to recipients with lower MELD scores. These interrelated factors make it challenging to pinpoint the exact contribution of NMP, underscoring the need for a nuanced interpretation of the data. All the above will result in a domino effect down the pipeline, including time and mortality on the waitlist, as reflected by fluctuating median waitlist times throughout the study period. Examining donor characteristics reveals a preponderance of “safe” grafts or “ideal,” as Chan and colleagues termed them, in the NMP group with more DBD livers than DCD (62% vs. 38%, respectively). Notably, median donor age (42 y NMP vs. 44 y SCS) and BMI (<30) were comparable, suggesting that marginal grafts remain underrepresented. Although the median Liver Donor Risk Index (LDRI) was significantly lower in NMP (adjusted: 1.7 vs. 2; p<0.001), the level of marginality (ie, % of macrosteatosis) in the DBD cohort was not reported. This limits the generalizability of the authors’ findings to higher-risk grafts, where NMP might prove most beneficial. The authors, who represent the elite among us, have provided valuable insights. However, certain contradictions warrant closer examination. They cite an ~$48,000 increase in NMP index hospitalization costs, attributing it largely to higher organ acquisition costs ($135,930). However, this assertion appears to conflict with their own definition of index hospitalization costs, which include fixed and variable expenses but exclude organ acquisition. Specifically, the TransMedics OCS System “service package,” costing roughly $84,000, was categorized under organ acquisition costs. In contrast, variable costs encompassed surgical supplies, anesthesia, postoperative care, laboratory tests, imaging, medications, and other related services. Further analysis underscores added complexities. In the SCS group, the median total cost (fixed and variable) for index hospitalization was $126,185 (IQR: $101,853–$190,478). Notably, 25% of cases exceeded $190,478, with 6 outliers reaching the $330K–$360K range. Among SCS recipients, 17% (n=25) were already in the ICU before transplant, compared with only 10% (n=10) in the NMP group. This pretransplant ICU admission likely contributed to prolonged ICU and hospital stays after surgery, inflating costs and narrowing the median cost gap to about $48K. The multivariate analysis further confirmed that pretransplant inpatient or ICU admissions were the only 2 independent predictors of renal replacement therapy (RRT) after transplant—a key driver of hospital resource utilization. This underscores the importance of accounting for pre-existing clinical factors when interpreting cost differences and evaluating the financial implications of adopting new technologies like NMP. That said, reporting cost differences after propensity matching for MELD-score-at-transplant would have been more appropriate, especially since many outcomes initially tied to NMP (eg, ICU/hospital stays, cryoprecipitate use, blood products) lost significance or became less pronounced when adjusted. Notably, ischemic cholangiopathy rates were insignificant between groups and reported only in DCD livers, not in DBD, raising questions about the necessity of NMP use in such high-quality grafts, particularly when the added costs and resource utilization are considered. The authors highlight a dramatic reduction in post-reperfusion syndrome (adjusted: 4.6% in NMP vs. 33.6% in SCS; p<0.001). This observation is probably attributed to shorter cold ischemia times (adjusted: 137.5 min for NMP vs. 355.5 min for SCS; p<0.001) and underscores the logistical advantages of NMP. However, the lack of granular data on marginal grafts, such as the prevalence of macrosteatosis, tempers these findings. Perhaps the study’s most intriguing narrative—though secondary to patient outcomes—is the potential improvement in surgeon and team quality of life. Daytime operations and streamlined logistics are undeniably attractive and, foremost, improve patient safety, yet these benefits must be weighed against the considerable financial and operational challenges of adopting NMP. Beyond the hype, Gao and colleagues deliver a thought-provoking exploration of NMP’s integration into liver transplantation. The promise of NMP is remarkable, but its value proposition must be rigorously validated through robust, multicenter studies that account for the complexities of real-world transplantation. As we all long for the day that Dr. Shaw is still waiting for, the transplant community must resist the allure of transformative technology without critically examining its implications. Only then can we determine whether the juice is truly worth the squeeze.