Liver transplantation remains the gold standard treatment for end-stage liver disease, yet organ shortages continue to limit access and increase waitlist mortality. Donation after circulatory death (DCD) has emerged as a critical strategy to expand the donor pool. However, long-standing concerns regarding warm ischemia—particularly donor time to death (TTD) following withdrawal of life-sustaining treatment—have shaped organ acceptance practices. Conventional wisdom has held that shorter TTD is better. This landmark study published in Transplantation Direct challenges that assumption using national United Network for Organ Sharing (UNOS) registry data spanning 2010 to 2025 .
The investigators analyzed 8,489 adult recipients of DCD liver-only transplants with at least one year of follow-up. An additional 41,443 potential donors were evaluated to assess utilization patterns. The median donor TTD was 13 minutes (IQR 9–17 minutes). Using advanced statistical modeling—including restricted cubic splines and multivariable Cox regression—the researchers examined nonlinear associations between TTD and 1-year graft survival, patient survival, early graft loss, and hospital length of stay.
Contrary to prevailing belief, shorter TTD was associated with inferior 1-year graft survival. Prolonged TTD, by contrast, was not associated with worse short-term or long-term outcomes. This finding persisted after adjusting for a wide range of donor and recipient confounders, including donor age, BMI, cause of death, machine perfusion use, recipient MELD score, ICU status, and transplant center effects. Even when functional TTD (defined as systolic blood pressure <50 mmHg until cold flush) was analyzed, no significant adverse association was identified.
Importantly, prolonged TTD did not negatively impact outcomes even in livers recovered through super-rapid recovery (SRR), where normothermic regional perfusion (NRP) was not used. In the NRP subgroup (703 recipients), no association was found between TTD and 1-year or 5-year graft or patient survival. These findings suggest that the liver may tolerate longer agonal periods better than previously assumed.
The authors propose a compelling physiological hypothesis. Donors with very short TTD may represent patients with catastrophic brainstem injury who do not meet formal brain death criteria but deteriorate rapidly. Such donors may experience profound inflammatory cascades and cytokine storm prior to circulatory arrest. When combined with DCD-related ischemia-reperfusion injury, this dual insult may render grafts more vulnerable, explaining the observed inferior outcomes in short-TTD donors.
While prolonged TTD did not impair transplant outcomes, utilization data revealed a different story. Multivariable logistic modeling of over 37,000 SRR donors demonstrated a sharp decline in liver utilization once TTD exceeded 10–15 minutes. This decline was statistically significant and independent of other donor characteristics. In other words, clinicians appear to be declining livers based on prolonged TTD despite no evidence of worse posttransplant outcomes.
Simulation modeling quantified the potential consequences of this practice. Among donors with TTD 15–30 minutes, the actual acceptance rate was 29.4%. If these offers had been treated identically to donors with TTD under 10 minutes, the predicted acceptance rate would have risen to 34.4%—a 17.1% relative increase. This translates to an estimated 654 additional liver transplants during the study period.
For donors with TTD 30–45 minutes, the actual acceptance rate was only 12.1%. The predicted acceptance rate under a no-TTD-bias model was 30.6%, representing a 152% relative increase and an estimated 547 additional transplants. These findings suggest a substantial underutilization of potentially viable DCD livers.
The study also revealed important differences between SRR and NRP cohorts. In the NRP group, shorter TTD was associated with decreased utilization. The authors hypothesize that injured livers in short-TTD donors may fail NRP viability assessment criteria, resulting in nonuse but preventing inferior outcomes. This highlights how NRP and machine perfusion technologies function as a safety net—allowing objective graft assessment before transplantation.
The implications for transplant practice are significant. Organ procurement organizations and transplant centers may need to reconsider rigid TTD thresholds. Given that prolonged TTD did not compromise 1-year or 5-year survival, avoiding TTD-based decline could safely expand the donor pool. Moreover, broader adoption of NRP and advanced perfusion technologies could further mitigate risk and maximize organ recovery.
The study’s strengths include its large national dataset, sophisticated nonlinear modeling, and comprehensive confounder adjustment. Limitations include its retrospective design and potential selection bias, although similar findings in UK cohorts support external validity.
In conclusion, this pivotal analysis challenges entrenched transplant dogma. Shorter TTD was paradoxically associated with inferior graft survival, while prolonged TTD did not worsen outcomes. Yet, utilization drops dramatically beyond 15 minutes of TTD, representing missed opportunities for lifesaving transplantation. Expanding acceptance criteria and leveraging normothermic regional perfusion could substantially increase safe DCD liver utilization in the United States and beyond .
