Taner, C. Burcin

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.

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.

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 .

Hepatic steatosis, characterized by the accumulation of triacylglycerol in hepatocytes, complicates liver transplantation by increasing the risk of ischemia-reperfusion injury (IRI), leading to suboptimal graft outcomes. This condition has become a major cause of liver graft discarding, exacerbating the ongoing organ shortage for transplantation. Recent advances in ex vivo normothermic perfusion machines (NMPs) have provided promising solutions for reconditioning and preserving steatotic liver. NMP supports cellular metabolism and mitigates IRI by maintaining the physiological conditions. In addition, pharmacological strategies to reduce hepatic steatosis have been explored to increase graft viability. In this review, we summarize current insights into hepatic lipid metabolism and the molecular mechanisms underlying steatosis, while discussing emerging pharmacological defatting approaches. These interventions have the potential to address the challenges posed by hepatic steatosis, improve graft quality, expand the availability of transplantable livers, and enhance clinical outcomes of transplant candidates. Finally, we highlight current limitations and outline directions for future research and clinical applications.

Extracorporeal membrane oxygenation (ECMO) use during liver transplantation is a complex and evolving aspect of critical care. This retrospective analysis presents the largest North American case series to date, offering a detailed comparison of survival outcomes in liver transplant (LT) patients supported by ECMO. A total of 15 patients were supported with ECMO, eight were supported on venoarterial (VA) ECMO and the remaining seven on venovenous (VV) ECMO. The median duration of ECMO support was 10 days. Mean intensive care unit (ICU) and hospital stays were 34.8 (interquartile range [IQR]: 1–158) and 49.2 days (IQR: 1–121), respectively. Overall survival was 33.3%, comparable to published rates (20–30%). Survival was based on ECMO initiation timing: preoperative 33.3% (1/3); intraoperative 50% (3/6); postoperative, 16.6% (1/6). All the patients (five) discharged from hospital were alive at 1 year follow-up. Significant ECMO-related complications included acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) (40%, n = 6/15), neurological complications (40%, n = 6/15), and bleeding requiring transfusion (26.6%, n = 4/15). Literature review suggests better outcomes with intraoperative or postoperative ECMO. While ECMO use is increasing in LT, outcomes remain poor. Improved survival may depend on careful patient selection, optimal timing of initiation, and distinguishing reversible pathology from irreversible one.

Despite European colorectal liver metastases (CRLM) transplant trials having been performed entirely using deceased donor liver transplant (DDLT), there has been speculation about whether similar results can be achieved in the United States, given the lack of MELD score prioritization. A formal transplant protocol for unresectable CRLM was implemented in our center at the start of 2022 with the plan to utilize DDLT. Between 2022 and 2025, 86 patients with CRLM were referred to our program, and 19 patients underwent a formal transplant evaluation. Median time from listing until transplant was 31 days (range 3–115 d). Median allocation MELD was 8 (range 6–15). The donor livers were from DCDs, older donors, or National Share livers, which had been declined by all other centers. All but 2 of the cases underwent advanced perfusion. There were no cases of primary nonfunction, postreperfusion syndrome, acute kidney injury, hepatic artery thrombosis, or ischemic cholangiopathy. The length of stay for the median posttransplant was 5 days. Graft and patient survival were 100% at the time of maximal follow-up. Recurrence developed in 3 recipients (25.0%), 1 of whom was treated and has no evidence of disease. These findings support the viability of DDLT for CRLM using advanced perfusion, contingent on strict protocol adherence. Center-specific waitlist dynamics must inform the choice between DDLT and living donor liver transplant (LDLT).

ABSTRACTBackground and AimsOne strategy to minimize the risk of posttransplant lymphoproliferative disorder (PTLD) is to avoid an Epstein–Barr Virus (EBV) mismatch through kidney paired donation. We aimed to estimate the incidence of PTLD in EBV‐negative kidney transplant recipients with EBV‐positive donors (D+/R−) and evaluate the excess risk of death following the occurrence of PTLD.MethodsWe included adult patients in OPTN database who underwent kidney transplants between 2012 and 2022. Cox regression analysis was employed to evaluate the impact of EBV serostatus on the development of PTLD, and to assess mortality following PTLD diagnosis in D+/R− individuals.ResultsA total of 179 068 patients were included, with 92.8% in the R+, 6.4% in the D+/R−, and 0.8% in the D−/R− group. D+/R− exhibited a significantly higher risk of PTLD compared to R+ and D−/R− groups. D+/R− had a greater risk of PTLD when compared to D−/R− recipients (aHR: 3.82; p < 0.001). Among D+/R− recipients, those who developed PTLD had a significantly higher risk of mortality (aHR: 2.28; p < 0.001 in deceased donor kidney transplant [DDKT] and aHR: 5.22; p < 0.001 in living donor kidney transplant [LDKT]).ConclusionsD+/R− recipients have nearly a fourfold higher risk of PTLD compared to D−/R− recipients, suggesting that choosing an EBV D−/R− transplant could reduce the PTLD risk by about 73%. This data is crucial for counseling EBV‐negative patients considering kidney paired donation to avoid an EBV serostatus mismatch.

Background. The availability of in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) has revolutionized donation after circulatory death (DCD) liver transplant (LT). While some have suggested that NRP and NMP may represent competing technologies for DCD LT, there are many scenarios where these technologies can function in a complementary manner. Methods. Between January 2022 and March 2024, 83 DCD LTs were performed using NRP (62 NRP alone and 21 NRP + NMP) and were compared with 297 static cold storage (SCS) DCD LTs. NRP + NMP was used in scenarios with (1) long travel distances, (2) complicated transplant recipients, or (c) the need for additional liver graft recovery in “marginal” cases. Results. Ischemic cholangiopathy was lower in the NRP alone group (0%) and the NRP + NMP group (0%) compared with the SCS group (16.8; P < 0.001 and P = 0.04, respectively). In addition, early allograft dysfunction, number of packed red blood cells transfused, and acute kidney injury were lower in the NRP alone and NRP + NMP groups compared with the SCS group. Graft survival was higher in cases where NRP was used than in cases where SCS was used ( P = 0.016). In all the cases where lactate remained elevated at the end of NRP (mean 8.2 ± 2.0), it ultimately normalized at the end of NMP (0.92 ± 0.56). Conclusions. The present study demonstrates lower rates of ischemic cholangiopathy and improved graft survival with NRP alone or NRP + NMP compared with SCS when using liver grafts from DCD donors. It also demonstrates that excellent outcomes can be achieved with sequential NRP + NMP in cases with prolonged travel distances, complicated recipients, or when there is a need for additional liver recovery in “marginal” cases.

There is a paucity of data on the impact of cold ischemia time before the initiation of normothermic machine perfusion (NMP), particularly in more susceptible organs such as livers from donation after circulatory death (DCD) donors. The present analysis aimed to investigate the impact of prolonged time from cross-clamp until NMP start on early allograft dysfunction and other peri–liver transplant (LT) outcomes. All DCD LT performed and placed on NMP at Mayo Clinic Arizona, Florida, and Rochester from January 2022 to March 2024 were included. The decision was made a priori to divide the population into 2 groups based on terciles: typical cross-clamp to on-pump time (lower 2 terciles) versus prolonged cross-clamp to on-pump time (upper tercile; >2 h 45.6 min). Three hundred eighty-four DCD LT undergoing NMP met the inclusion criteria. The rate of early allograft dysfunction was significantly higher in the prolonged cross-clamp to on-pump group (51.2%) compared to the typical cross-clamp to on-pump group (37.6%) (p = 0.01). The prolonged cross-clamp to on-pump group also had higher rates of acute kidney injury and the number of packed red blood cells transfused during LT. No significant difference in ischemic cholangiopathy (2.4% vs. 3.1%; p = 0.68) or graft survival at 12 months was seen between the prolonged cross-clamp to on-pump and typical cross-clamp to on-pump group, respectively. Following cross-clamp, DCD liver grafts should be placed on the NMP pump as quickly as is safely and logistically possible. In cases where delays are unavoidable, such as waiting for biopsy results or liver reallocation with another center, acceptable results can still be achieved, and therefore, livers with prolonged times should still be used.

ABSTRACT The management of hepatic adenoma in transgender individuals undergoing gender-affirming hormone therapy remains unclear, especially whether treatment should be based on sex assigned at birth or therapy patient received. We presented a transgender man, female at birth, with hepatic adenomatosis with molecular profile differed from typical adenomas in cisgender males on testosterone. Discontinuing testosterone led to autoinfarction of the adenoma, allowing the avoidance of invasive treatments and resumption of gender-affirming hormone therapy. This case underscores the necessity for personalized care in the growing transgender population and challenges current consensus of treatment based on sex assigned at birth, emphasizing a tailored approach.