Advancing Donation After Circulatory Death Liver Transplantation: National Evidence Supporting Normothermic Regional and Machine Perfusion as Standards of Care

Highlight

This national comparative analysis of 4,632 donation after circulatory death (DCD) liver transplants in the United States demonstrates that both normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) significantly improve graft survival compared to conventional super rapid recovery with static cold storage (SRR-SCS). Importantly, no significant survival differences were observed between NRP and NMP, affirming their complementary utility. This evidence supports the adoption of both techniques as new standards of care in DCD liver transplantation.

Study Background

Liver transplantation using grafts from donation after circulatory death donors has historically been limited by inferior outcomes relative to donation after brain death donors. A major challenge has been the increased incidence of ischemic-type biliary injury, leading to graft dysfunction and failure. Improved procurement and preservation strategies to mitigate ischemia-reperfusion injury have become critical to enhancing DCD liver graft viability and outcomes. Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) have emerged as promising approaches, maintaining organs at physiologic temperature with oxygenated blood or perfusate to improve viability and reduce ischemic injury.

Study Design

This retrospective cohort study analyzed national data from the United Network for Organ Sharing (UNOS) registry covering 2022 to 2024. The study population included 4,632 DCD liver transplant cases stratified by procurement and preservation methods: super rapid recovery (SRR) vs. normothermic regional perfusion (NRP) for procurement, and static cold storage (SCS) vs. normothermic machine perfusion (NMP) for preservation. NMP cases were further divided into on-site initiation and back-to-base initiation. On-site NMP was directly recorded in UNOS, while NRP and back-to-base NMP were identified using surrogate markers. Propensity score matching was applied to balance covariates and compare graft survival (GS) and overall survival (OS) across cohorts.

Key Findings

Among identified cases, the most common approach was SRR-NMP (56.9%), followed by SRR-SCS (20.2%), NRP-SCS (12.1%), and NRP-NMP (10.8%).

Comparative analyses revealed that:

• SRR-NMP was associated with significantly improved graft survival compared to SRR-SCS (hazard ratio [HR] 0.54; 95% confidence interval [CI] 0.32–0.92), highlighting the benefit of normothermic machine preservation over traditional cold storage following SRR procurement.
• NRP followed by SCS also showed a significant reduction in graft loss risk versus SRR-SCS (HR 0.42; 95% CI 0.29–0.61), underscoring the efficacy of normothermic regional reperfusion during procurement in improving graft outcomes.
• Between NRP-SCS and SRR-NMP, there were no statistically significant differences in graft survival, suggesting comparable effectiveness of these two modern approaches.
• Adding NMP to livers procured with NRP (NRP-NMP) did not further improve outcomes compared to NRP followed by SCS alone, indicating that NMP may not provide additional benefit after NRP.

Overall survival outcomes mirrored graft survival trends. These findings establish that both NRP and NMP are superior to the historical SRR-SCS approach and serve complementary roles rather than being mutually exclusive alternatives.

Expert Commentary

This pioneering national analysis in the U.S. substantiates the clinical value of normothermic perfusion strategies in overcoming the ischemic challenges inherent in DCD liver transplantation. By maintaining the organ in a physiologic state at procurement (NRP) or during preservation (NMP), these techniques mitigate ischemia-reperfusion injury, particularly to the biliary epithelium, which has resulted in historically higher rates of biliary complications and graft loss.

The comparable graft survival between NRP and NMP suggests that centers may tailor their use based on logistics and resources: NRP requires specialized surgical expertise and facilities for in situ reperfusion, while NMP offers the flexibility of ex vivo organ assessment and preservation.

However, the lack of incremental benefit from combining NRP with NMP indicates a potential ceiling effect in ameliorating ischemic injury, and that resource allocation might prioritize deploying either technique effectively rather than both in sequence.

Limitations include reliance on surrogate markers in UNOS data, potential unmeasured confounders, and variations in machine perfusion protocols across centers. Nonetheless, the large sample size and rigorous propensity matching strengthen the validity of these findings.

Conclusion

This comprehensive national comparative study confirms that both normothermic regional perfusion during procurement and normothermic machine perfusion during preservation significantly improve graft survival after DCD liver transplantation compared to the historic standard of super rapid recovery with static cold storage. Their complementary roles enable transplantation centers to adopt strategies tailored to their infrastructure to mitigate ischemic biliary injury effectively.

These results support the adoption of NRP and NMP as new standards of care in U.S. DCD liver transplantation, with significant potential to expand the donor pool and improve transplant outcomes. Future prospective trials and cost-effectiveness analyses will further guide optimized protocol selection and implementation.

Funding and ClinicalTrials.gov

The study was supported by institutional funding; no specific clinical trial registration is reported. Authors disclose no conflicts of interest.

References

1. Acuna SA, Dayala H, Jones-Carr ME, et al. Normothermic Machine and Regional Perfusion in U.S. DCD Liver Transplantation: A National Comparative Analysis Supporting Adoption as Standard of Care. Ann Surg. 2026 Jun 23. PMID: 42335023.
2. Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation. Nature. 2018;557(7703):50-56.
3. Watson CJE, Jochmans I. Normothermic Regional Perfusion: Resuscitating Graft Function and Expanding Use of Extended Criteria Donor Organs. Am J Transplant. 2020;20(12):3256-3261.
4. Czigany Z, Schlegel A, Verbeke L, et al. Continuous Normothermic Regional Perfusion Versus Abdominal Normothermic Machine Perfusion in Donation After Circulatory Death Liver Transplantation: Current Evidence and Perspectives. Transplantation. 2022;106(8):1539-1549.