Croome, Kristopher P.

ABSTRACT Background With increasing use of donation after circulatory death (DCD) donor grafts, the need for accurate risk‐stratification tools in liver transplantation has become critical. Machine perfusion has been shown to improve both graft and patient survival. However, existing prediction models were developed in the static cold storage (SCS) era and their accuracy when using machine perfusion remains unknown. Our study aims to study if current scoring systems can predict graft and patient survival for DCD livers preserved using normothermic machine perfusion (NMP). Methods This was a retrospective study of patient and graft survival in a two‐center U.S. DCD NMP cohort ( n = 532) between January 2022 and December 2024. Predicted graft and patient survival rates were obtained from established risk scoring systems, including the United Kingdom DCD risk score (UK‐DCD), Early Allograft Dysfunction (EAD) Olthoff score, Liver Graft Assessment Following Transplantation (L‐GrAFT 7 ) score, Donor Risk Index (DRI), Balance of Risk (BAR) score, and Survival Outcomes Following Liver Transplant (SOFT) score. Model discrimination was assessed using receiver operating characteristic (ROC) curves (C‐statistics). Survival outcomes across risk strata were estimated and compared using Kaplan‐Meier (KM) analysis. Results Across scoring systems, predicted survival consistently underestimated actual graft and patient survival in the NMP DCD cohort. The DRI, SOFT, EAD and L‐GrAFT 7 did not demonstrate predictive value. UK‐DCD predicted ≤85% and <40% 1‐year graft survival for its high‐risk and “futile” groups, whereas observed rates were 93.7% and 86.8%. BAR low‐risk predicted >60% 5‐year survival but 94.2% was observed; the high‐risk group predicted <60% and observed was 53.3%. Despite underestimations and generally poor C‐statistics, in KM stratification, high‐risk groups still showed statistical differences in the UK‐DCD categories ( p = 0.007), and in SOFT score groups ( p < 0.001). No statistical difference was seen in BAR ( p = 0.36), DRI ( p = 0.36), EAD ( p = 0.12), or L‐GrAFT 7 ( p = 0.75). Conclusion Existing liver transplant risk scores show limited predictive value for donor‐related risk factors in the NMP era, whereas recipient‐related factors remain somewhat predictive, despite overestimating risk. Early allograft dysfunction metrics were not reliable predictors of short or long‐term outcomes. Future risk models should integrate machine‐perfusion parameters and refined donor variables to reflect outcomes more accurately in contemporary DCD liver transplantation.

Normothermic Regional Perfusion (NRP) is emerging as a game-changer in enhancing outcomes for Donation after Circulatory Determination of Death (DCDD). NRP maintains physiological conditions through perfusion with oxygenated blood, outperforming conventional super-rapid recovery techniques significantly improving outcomes and organ utilization. Despite its clinical benefits, widespread adoption of NRP is impeded by heterogeneous organizational, legal, and ethical frameworks. At the ESOT Bucharest Consensus Conference, leading experts in transplantation achieved consensus on 130 relevant NRP-related open issues to facilitate its implementation and guide global practice. Key recommendations include criteria for adoption of NRP, minimal requirements, procedures to be adopted before and during NRP, donor organ evaluation criteria and sequence of organ harvesting. Consensus extends to procedural components (including the configuration of perfusion parameters and strategic team coordination), ethical integrity of NRP in the context of the dead donor rule and key unmet needs for future developments. While significant strides were made in unifying practice, unresolved issues regarding maximum warm ischemic time and variability in legal standards indicate avenues for future research. This consensus underscores the imperative for global standardization in NRP application, promising to elevate the success rates of organ transplants and establish NRP as a foundational element in the evolution of DCDD.

Donation after circulatory death (DCD) liver transplants (LTs) are associated with increased risk of post-LT acute kidney injury (AKI). This retrospective study aimed to examine the effect of continuous normothermic machine perfusion (NMP) on the incidence and stage of AKI in DCD LT. The incidence of AKI within 48 hours was compared between 507 NMP-DCD and 472 static cold storage (SCS)-DCD LT transplanted between January 1, 2016, and December 31, 2024. AKI developed in 337 (34%) patients. On univariate analysis, AKI rate was lower in NMP-DCD compared with SCS-DCD (28% vs. 41%, p <0.001). Stages 2 and 3 AKI at 48 hours and renal replacement therapy (RRT) within the first 3 weeks were also lower in NMP-DCD compared with SCS-DCD ( p <0.001). After adjusting for multiple recipient, donor, and intraoperative factors using multivariate logistic regression, NMP-DCD was independently associated with a 37% lower odds of AKI (aOR: 0.63, CI: 0.46–0.85, p =0.003) and 55% lower odds of stages 2 and 3 AKI (aOR: 0.45, CI: 0.29–0.69, p <0.001) compared with SCS-DCD. To mitigate for the era effect and other unmeasured confounders, an inverse probability of treatment weighting (IPTW) analysis was performed using a propensity score model with average treatment effect (ATE). After weighting for multiple factors, NMP-DCD was associated with lower odds of AKI at 48 hours (OR: 0.65, CI: 0.53–0.81, p =0.001), stages 2 and 3 AKI at 48 hours (OR: 0.60, CI: 0.42–0.85, p =0.02), and RRT at day 7 (OR: 0.31, CI: 0.13–0.65, p =0.003) compared with SCS-DCD. In conclusion, compared with SCS-DCD, NMP-DCD was independently associated with lower odds of AKI at 48 hours, of stages 2 and 3 AKI at 48 hours from LT, and of RRT requirement at day 7 from LT, an effect that extended for the first 3 post-LT weeks.

Abstract Background Machine perfusion represents the most significant breakthrough in liver transplantation (LT) since the discovery of cyclosporin. Yet, the optimal perfusion strategy remains unsettled. Randomized trials demonstrate that hypothermic oxygenated perfusion (HOPE) improves graft survival and function and reduces ischemic cholangiopathy, whereas normothermic machine perfusion (NMP) decreases post-transplant injury. Real-world comparisons are lacking and challenging due to heterogeneity in donor-recipient risk profiles and regional differences. Aims To compare real-world outcomes of HOPE and NMP in LT. Methods We analyzed consecutive NMP-preserved LTs from seven North American centers between 2021 and 2024. We compared NMP to the European HOPE-REAL cohort, comprising HOPE-treated LTs from 22 centers between 2012 and 2021. Analyses were stratifyied by graft type and risk category and adjusted for donor age, donor risk index, and balance of risk score using entropy balancing. Results A total of 470 NMP and 1202 HOPE-treated grafts were analyzed, revealing major differences in risk profiles (Figure 1). In NMP, death-censored graft survivals at 1, 2, and 3 years were &gt;95% in donation after brain death (DBD) and &gt;94% in donation after circulatory death (DCD) grafts. Comparable outcomes were observed in the HOPE cohort with &gt;93%, in DBD, and &gt;87% in DCD after up to 3 years, despite significantly higher donor age and longer functional warm ischemia in the HOPE DCD cohort (Figure 2). After risk adjustment, death-censored graft survival remained similar between both modalities (Table 1). Non-anastomotic biliary stricture rates after DCD-LT were comparable (8.5% vs. 12.4%), independent of whether continuous or end-ischemic NMP was performed. Conclusion This first transatlantic real-world report demonstrates excellent outcomes with both NMP and HOPE despite higher graft risk in Europe. Machine perfusion is the new standard of care in LT, while further understanding is needed regarding the distinct benefits of each modality across risk profiles.Figure 1.Graft risk in NMP and HOPE stratified by graft type. Benchmark case was defined as primary transplant with MELD &lt;20 and BAR score &lt;9, extended criteria as either BMI &gt;30kg/m2, donor age &gt;65 years, CIT &gt;12h. DCD grafts were categorized as definedFor image description, please refer to the figure legend and surrounding text. Figure 2.Death-censored graft survival in liver transplantation following NMP and HOPE stratified by graft type. Abbreviations: NMP (Normothermic Machine Perfusion), HOPE (Hypothermic Oxygenated Perfusion), DBD (Donation after Brain Death), DCD (Donation after circulatory death)For image description, please refer to the figure legend and surrounding text. Table 1.Risk-adjusted comparison of death-censored graft survival between NMP and HOPE.For image description, please refer to the figure legend and surrounding text.

Importance Ischemia-reperfusion injury contributes to graft dysfunction after liver transplant. Hypothermic oxygenated perfusion (HOPE) has been shown to improve liver function, but its benefit in extended criteria donors in a US population remains unclear. Objective To assess whether back-to-base portal-venous HOPE impacts outcomes after liver transplant in the US. Design, Setting, and Participants The Bridge to HOPE Trial is a multicenter, randomized, open-label trial with 1-year follow-up. The study took place at 15 US liver transplant centers and patients were enrolled between January 2021 and May 2023. Central assessment of complications and cholangiograms for nonanastomotic biliary strictures (NAS) was blinded to treatment arm. Participants included 219 recipients of extended-criteria donor livers after brain death (DBD) and after circulatory death (DCD) who were randomized 1:1 to HOPE after static cold storage (SCS) (n = 109) or SCS only (n = 110). Randomization was performed after liver inspection and acceptance for transplant. Data were analyzed from December 2024 to July 2025. Intervention After SCS and transport, livers underwent portal-venous HOPE until implant, using the VitaSmart HOPE System. Main Outcomes and Measures The primary efficacy end point was early allograft dysfunction (EAD). Other main outcomes included model for early allograft function (MEAF) score, hospital length of stay (LOS), patient and graft survival, and biliary complications. Additional post hoc analyses were performed. Results Overall, 219 patients (82 female [37.4%] and 137 male[62.6%]) were included (DCD, 57 of 219 [26%]) with 97% (212 of 219) completing 12-month follow-up. EAD incidence was 20.2% (22 of 109) with HOPE vs 37.3% (41 of 110) with SCS (rate difference, −17.1%; 95% CI, −27.2 to −7.0; noninferiority P &amp;lt; .001; superiority P = .005). HOPE treatment led to significantly lower MEAF mean (SD) scores (HOPE group, 4.28 [1.75]; control group, 4.82 [1.85]; mean difference, −0.54; 95% CI, −1.02 to −0.06; P = .03) and shorter median LOS (hazard ratio, 1.32; 95% CI, 1.01-1.73; P = .04). NAS on imaging and 1-year survivals were comparable between groups (patients: HOPE group, 106 of 109 [97.2%] vs SCS, 106 of 110 [96.4%]; graft: HOPE group, 104 of 109 [95.4%] vs SCS, 102 of 110 [92.7%]). Post hoc analyses showed numerically less graft loss due to NAS after HOPE (4 vs 1) and less major complications (Clavien-Dindo classification ≥IIIa) per patient, respectively. Conclusions and Relevance Back-to-base portal-venous HOPE was compared with SCS alone for extended risk DBD and DCD livers. The HOPE approach was safe and associated with reduced EAD, MEAF score, and LOS. These findings support the use of HOPE as a pragmatic strategy to improve early posttransplant outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT05045794 .

Normothermic regional perfusion (NRP) adoption for donation after circulatory death (DCD) liver transplantation in the United States has been growing, but there remains a higher rate of non-utilization of NRP DCD liver grafts as compared with donation after brain death liver grafts. Six transplant centers and 1 organ procurement organization (OPO) with substantial NRP liver procurement experience performed retrospective reviews of all NRP procurement attempts from September 1, 2021, until March 1, 2024, identifying opportunities for utilization. Five of the 6 transplant centers had prospectively collected data on all accepted livers with NRP intent. The transplant center's intention to utilize DCD donors included 329 livers accepted for transplantation before withdrawal, 252 (76.6%) potential donors expired within the hospital timeframe for donation, and 168 (66.7%) livers were transplanted. Fifty-seven opportunities for utilization were identified by transplant centers, plus 11 from the OPO: most were due to exceeding a functional warm ischemic time limit (n=26), other reasons (n=17), and functional assessment (n=16). The lessons learned by centers in this study provide guidance for newer NRP centers and for OPOs in identifying opportunities for utilization of NRP DCD grafts that have historically been declined.

Liver transplantation has emerged as a curative treatment option for selected patients with unresectable hepatic malignancies beyond hepatocellular carcinoma, marking a paradigm shift in transplant oncology. For colorectal cancer liver metastases (CRLM), prospective trials have demonstrated that highly selected patients achieve 5-year OS rates of 60–83%, with the Oslo score identifying optimal candidates for transplantation. Perihilar cholangiocarcinoma (pCCA) has been successfully treated using strict patient selection criteria combined with neoadjuvant therapy, achieving 5-year OS rates of 50–68%, though emerging data suggests chemotherapy-based approaches may be preferable to radiation in selected cases. Intrahepatic cholangiocarcinoma (iCCA), previously considered a contraindication to transplantation, can now achieve excellent long-term outcomes (79.5% 5-year OS) in patients demonstrating sustained response to neoadjuvant chemotherapy and radioembolization, with metabolic tumor volume < 70 cm3 serving as an objective prognostic marker. Across these three emerging indications, successful outcomes depend on strict patient selection based on tumor biology, intensive multimodal neoadjuvant therapy, multidisciplinary evaluation in high-volume centers, and careful observation during treatment to exclude patients with aggressive disease. This evolution in transplant practice offers curative intent therapy to patients that previously only had palliative therapeutic options, fundamentally transforming hepatobiliary and oncologic surgery.

ABSTRACT During normothermic regional perfusion (NRP), lactate is the most commonly used liver viability marker. Lactate production from pyruvate breakdown in erythrocytes is not suspended during pRBC storage. By transfusing blood at a variety of stored ages, variable amounts of lactate are added to the NRP circuit and may influence serial lactate measurements. Sixteen DCD donors undergoing NRP were enrolled in a prospective study. Samples were drawn from pRBC bags prior to use in the NRP circuit and were tested for lactate values. Lactate values of the NRP circuit perfusate were also assessed Q15 min. Lactate values of the pRBCs varied from 4.4 mmol/L to >20 mmol/L and were strongly correlated with the age of the stored blood ( r 2 = 0.74). Donors in which the pRBCs were > = 20‐days from expiration (Newer Blood group) had a significantly lower lactate at 60 min of NRP compared to donors in which pRBCs were <20 day from expiration (Older Blood group) (4.0±2.0 mg/dL vs. 6.3±2.3 mg/dL; p = 0.048). If the lactate is not decreasing as anticipated, transfusion of older pRBC should be entertained as one possible explanation. In cases where the liver seems acceptable for transplantation, additional lactate testing with longer time on NRP or sequential NRP/NMP should be considered in lieu of declining the liver outright.