Due to donor liver shortage, donation after circulatory death (DCD) livers are increasingly used for liver transplantation (LT). However, non-anastomotic biliary strictures (NAS) are more often observed after DCD LT, which can cause serious morbidity. To provide early adequate NAS-treatment, reliable NAS classification is pivotal. Therefore, the current study determined the clinical applicability of two radiological NAS-classification systems, namely the system of Croome and the Groningen system. Patients included in the dual hypothermic oxygenated perfusion (DHOPE)-DCD trial (NCT02584283) who underwent LT between January 2016 and July 2019, and in whom per-protocol biliary imaging studies 6 months post-LT were available, were included in the study. NAS severity according to both scoring systems was scored by two independent radiologists, and the correlation for each system with clinical outcomes was made. In total, 133 patients were included. In our study population, both systems showed good correlation with clinical outcomes, as the highest rates of NAS-related cholangitis and biliary interventions were observed in patients with diffuse necrosis or multifocal progressive disease according to the Croome classification, and likewise in the moderate and severe NAS subgroups in the Groningen classification. Worst 5-year graft and patient survival rates were observed in the case of diffuse necrosis (77

Objective: To report real-world data on hypothermic oxygenated perfusion (HOPE) and normothermic machine perfusion (NMP) in liver transplantation (LT). Summary Background Data: Real-world comparisons between HOPE and NMP are limited and methodologically challenging due to heterogeneity in donor and recipient risk profiles and regional differences in practice patterns. Methods: This international cohort study analyzed consecutive NMP-preserved LTs performed at 15 predominantly North American centers between 2021 and 2025. Outcomes were compared with the European HOPE-REAL cohort, comprising HOPE-treated LTs from 22 centers between 2012 and 2021. Risk-adjusted analyses were performed, stratified by graft type and risk category. Imbalances in baseline characteristics were addressed using entropy balancing. Results: A total of 954 NMP-treated and 1202 HOPE-treated grafts were analyzed, revealing substantial differences in donor risk. Extended-criteria DBD grafts accounted for 30% versus 64%, and futile DCD grafts for 10% versus 30%, in the NMP and HOPE cohorts, respectively. In the NMP cohort, death-censored graft survival at 1, 2, and 3 years exceeded 96% for DBD grafts and 94% for DCD grafts. Comparable outcomes were observed in the HOPE cohort, with 93% survival in DBD and 87% in DCD grafts at up to 3 years, despite significantly higher donor risk in the HOPE-DCD cohort. After risk adjustment, death-censored graft survival remained similar between both modalities across graft types and risk categories. Conclusions: Real-world data on HOPE-treated and NMP-treated LT demonstrate excellent outcomes. Nevertheless, compared with HOPE, further high-quality evidence and longer preservation time is needed to substantiate the clinical benefits of NMP in high-risk grafts.

Sarcopenia and frailty are common in liver transplant candidates and often deteriorate early posttransplantation, negatively affecting recovery and survival. Since 5 years, we refer liver transplant recipients who, despite being medically stable, are considered unfit for safe discharge home because of physical, social, or functional limitations for continued care at an independent rehabilitation hospital. This retrospective observational study evaluated safety and functional outcomes of this rehabilitation program and explored clinical characteristics associated with referral. We reviewed all adult liver transplant recipients at University Hospitals Leuven between July 2020 and 2025. Collected data included demographics, frailty, BMI, neuropathy, laboratory model for end-stage liver disease/Stanford Integrated Psychosocial Assessment for Transplant scores, ICU/hospital length of stay, and referral for inpatient rehabilitation. For referred patients, rehabilitation duration and functional outcomes were analyzed. Of 380 liver transplant recipients, 34 (8.9%) were referred for inpatient rehabilitation. Median rehabilitation duration was 30 days [interquartile range (IQR): 21-40]. Significant functional improvements were observed, with 6-min walk distance increasing from 130 (IQR: 33-225) to 300 (IQR: 220-423; P ≤ 0.001) m, and Tinetti scores improving from 21 (IQR: 18-23) to 25 (IQR: 22-27; P = 0.001). No mortality occurred during rehabilitation. Four patients were readmitted for reasons unrelated to rehabilitation. Multivariable logistic regression identified lower pretransplant BMI and higher frailty scores as independent predictors of referral, with a trend toward an association with peroneal neuropathy. Continued inpatient rehabilitation following liver transplant is feasible, safe, and associated with clinically relevant functional improvements. Pretransplant malnutrition and frailty, as well as posttransplant peroneal neuropathy, may represent targets to facilitate posttransplant recovery.

This study is a retrospective analysis of a cohort of patients presenting with transplant renal dysfunction related to proximal aorto-iliac occlusive disease and treated with angioplasty and stenting. Primary outcomes included changes in intrarenal resistive index (RI) and laboratory and clinical data including serum creatinine level, systolic and diastolic blood pressure, and number of anti-hypertensive drugs before and after endovascular intervention. Secondary outcomes included overall patient and transplant kidney survival. Endovascular intervention was successful in all 26 included patients and associated with a significant increase in intrarenal RI in the upper pole (0.65 before vs. 0.74 after stent; P = 0.0009), in the interpolar region (0.64 before vs. 0.74 after stent; P = 0.0028), and in the lower pole (0.63 before vs. 0.76 after stent; P = 0.0002). In addition, there was a significant improvement in serum creatinine (2.29 mg/dL before vs. 1.49 mg/dL 6 weeks after stent; P < 0.0001) and systolic blood pressure (149.6 mmHg before vs. 139.8 mmHg 1 week after stent; P = 0.0233). Overall estimated transplant kidney survival was 95% at 5 and 10 years of follow-up. Endovascular intervention is a very effective and durable treatment option for the management of transplant renal dysfunction related to proximal aorto-iliac occlusive disease.

BACKGROUND:Sarcopenia and obesity are prevalent in end-stage-liver-disease (ESLD) patients undergoing Liver Transplantation (LT), contributing to morbidity and mortality. Although LT restores liver function, sarcopenia and obesity often persist. Body mass index (BMI) is unreliable in ESLD for assessing adiposity, necessitating alternative measures. Visceral-to-subcutaneous adipose tissue (VAT/SAT) ratio affects outcomes, with VAT associated with poorer cardiovascular health and survival. This study investigated long-term changes in body composition post-LT and their associations with survival and hospital/ICU stay. METHODS:A single-center retrospective cohort analyzed 81 adults undergoing LT (2009-2015). Body composition was assessed via CT/MRI at L3 level pre-LT and longitudinally up to 10y post-LT. Sarcopenia was defined using sex-specific skeletal muscle index (L3-SMI) thresholds. VAT and SAT areas quantified fat distribution. Outcomes included ICU/hospital stay and survival. Longitudinal changes were modeled using linear mixed models. Associations resulted from survival analysis and Spearman correlations. RESULTS:Pre-LT, 61% were sarcopenic, 53% had BMI ≥ 25 kg/m2, and 19% had sarcopenic obesity. Post-LT, L3-SMI declined, partially recovered, but remained below baseline. BMI decreased initially, then increased. VAT rose for 2-4y, then declined; SAT increased steadily. VAT/SAT ratio increased modestly early, then declined after ∼4.5y. Pre-LT sarcopenia predicted lower survival; post-LT didn't. Higher pre-LT VAT was associated with prolonged ICU stay. Elevated pre-LT VAT/SAT ratio correlated with longer ICU/hospital stays. CONCLUSIONS:Sarcopenia persists long after LT and is associated with reduced survival. Unfavorable fat distribution was associated with longer hospital/ICU stay. Early diagnosis and targeted management of sarcopenia and visceral adiposity seem promising to improve post-LT outcomes.

Abstract Background Ferroptosis has emerged as a promising therapeutic target in IRI. However, it remains largely unclear how and when this iron-dependent regulated cell death manifests during IRI. Therefore, we explored malondialdehyde (MDA), a byproduct of lipid peroxidation, and glutathione peroxidase 4 (GPX4), as a marker of redox capacity, in multiple IRI models. With this explorative study, we aimed to uncover MDA dynamics in renal and hepatic IRI, which could provide valuable insights for future internal studies. Methods Historical plasma and tissue samples from rat and porcine models of renal and hepatic IRI were selected based on varying conditions of ischemic injury, reperfusion and perfusion. MDA was measured using a colorimetric assay with N-methyl-2-phenylindole, methanol, acetonitrile and hydrochloric acid and quantified at 595 nm. GPX4 protein concentrations were investigated using standard western blotting. Results In rat clamping models, plasma MDA concentrations revealed no difference between control and IRI settings. However, an increasing trend could be observed in tissue samples after IRI. Similarly, a decrease in tissue GPX4 concentrations was observed after IRI. In porcine studies, MDA concentrations were increased during reperfusion of kidneys exposed to prolonged warm ischemia and livers exposed to short periods of cold ischemia. Dynamic preservation could attenuate MDA concentrations. Conclusion We found that MDA and GPX4 are affected within the first hours after reperfusion, stressing the need for early sampling in studies focusing on characterizing ferroptosis. Moreover, MDA dynamics during organ perfusion revealed an increased vulnerability of ischemic organs to lipid peroxidation and a potential protective effect of dynamic preservation. These preliminary results should be confirmed in studies focusing on ferroptosis characterization, as notable observations regarding sample age and storage conditions and experimental design limit the validity of this study.

OBJECTIVE:To report the expanding application of nonvascularized rectus fascia allotransplantation (NVRF-alloTx) in solid organ transplant (SOT) and non-SOT patients and evaluate its effectiveness, integration, and immunologic response in complex abdominal and thoracic reconstruction. SUMMARY BACKGROUND DATA:Synthetic and biological meshes are limited by infection risk, long-term failure, donor-site morbidity, and high cost. NVRF-alloTx, first applied in intestinal/multivisceral-Tx with a 5.9% herniation rate, offers a simple and promising alternative for challenging defects. METHODS:This prospective single-center study included all consecutive patients undergoing NVRF-alloTx (2020-2025). Patients were divided into 2 groups: (1) reconstruction in SOT patients (simultaneous or elective closure post-SOT) and (2) reconstruction in non-SOT patients, without immunosuppression. NVRF-allografts were procured from deceased donors, preserved at 2°C, and implanted without HLA-matching. Primary endpoints were successful closure, graft failure, and functional outcome. Clinical and radiologic follow-up was performed, with HLA donor-specific antibody (HLA-DSA) testing and histology whenever available. RESULTS:Forty-seven NVRF-Tx procedures were performed in 41 patients using grafts from 48 deceased donors: group 1 (n=17) and group 2 (n=24). In 2 patients (4.9%), the graft did not integrate due to pancreatic leakage and vasopressor therapy. Others resulted in successful functional outcomes. Histology (n=5) showed graft integration through host fibrotic remodeling with neovascularization evident from 1 month after implantation. (De novo) HLA-DSA developed more frequently in non-SOT NVRF recipients than in SOT NVRF recipients. CONCLUSIONS:NVRF-alloTx is a versatile and effective reconstructive option for complex defects in SOT and non-SOT patients, providing an alternative to conventional meshes in challenging clinical scenarios.

OBJECTIVE:To report real-world data on hypothermic oxygenated perfusion (HOPE) and normothermic machine perfusion (NMP) in liver transplantation (LT). SUMMARY BACKGROUND DATA:Real-world comparisons between HOPE and NMP are limited and methodologically challenging due to heterogeneity in donor and recipient risk profiles and regional differences in practice patterns. METHODS:This international cohort study analyzed consecutive NMP-preserved LTs performed at 15 predominantly North American centers between 2021 and 2025. Outcomes were compared with the European HOPE-REAL cohort, comprising HOPE-treated LTs from 22 centers between 2012 and 2021. Risk-adjusted analyses were performed, stratified by graft type and risk category. Imbalances in baseline characteristics were addressed using entropy balancing. RESULTS:A total of 954 NMP-treated and 1202 HOPE-treated grafts were analyzed, revealing substantial differences in donor risk. Extended-criteria DBD grafts accounted for 30% versus 64%, and futile DCD grafts for 10% versus 30%, in the NMP and HOPE cohorts, respectively. In the NMP cohort, death-censored graft survival at 1, 2, and 3 years exceeded 96% for DBD grafts and 94% for DCD grafts. Comparable outcomes were observed in the HOPE cohort, with 93% survival in DBD and 87% in DCD grafts at up to 3 years, despite significantly higher donor risk in the HOPE-DCD cohort. After risk adjustment, death-censored graft survival remained similar between both modalities across graft types and risk categories. CONCLUSIONS:Real-world data on HOPE-treated and NMP-treated LT demonstrate excellent outcomes. Nevertheless, compared with HOPE, further high-quality evidence and longer preservation time is needed to substantiate the clinical benefits of NMP in high-risk grafts.

BACKGROUND:Medical assistance in dying (MAiD) is legally permitted in a growing number of jurisdictions, and in 6, it can currently be followed by organ donation. Organ donation following MAiD offers patients an opportunity to address transplant needs as a final act of altruism, but it also raises complex ethical questions that require strong safeguards to protect patients, professionals, and public trust. METHODS:We identified key ethical issues and safeguards by analyzing guidelines and protocols from the 6 countries where organ donation following MAiD is performed: Australia, Belgium, Canada, the Netherlands, New Zealand, and Spain. This article was developed under the auspices of the Ethics Committee of The Transplantation Society with medical, ethical, and legal experts from these countries. RESULTS:Three domains of ethical concern emerged: (1) safeguarding the integrity of patients' decision-making (voluntariness, informed consent, and how and when information is presented); (2) ethical governance of donation following MAiD (adherence to the Dead Donor Rule, death determination, and consent for premortem interventions); and (3) implications for care relationships and professional practice (end-of-life impacts, recipient information and donor anonymity, and professional support, including conscientious objection). Key recommendations include clear and consistent policies; a patient-centered, nondirective approach; rigorous eligibility and voluntariness assessments; and strict separation between MAiD and donation/transplantation teams. CONCLUSIONS:These recommendations provide practical guidance for implementing organ donation following MAiD in jurisdictions where it is practiced or being considered. They support patients' end-of-life wishes while safeguarding ethical and legal standards and maintaining trust in both MAiD and organ transplantation.

Ischemia-reperfusion injury (IRI) is a major clinical challenge in transplantation, vascular surgeries, myocardial infarction, and stroke. Disruption of energy and redox homeostasis triggers ferroptosis, a regulated, iron-dependent form of cell death, leading to organ dysfunction. We identify an early and transient increase of lipid peroxidation in human liver transplants and validate it as a therapeutic target. FXT-001, a ferroptosis inhibitor with dual radical and iron-trapping activity, provides robust protection in preclinical models, including ex situ perfusion of porcine liver and lung grafts. In a split ex vivo machine perfusion setting using declined human donors, FXT-001 treatment preserves graft viability, whereas untreated lungs deteriorate. We also develop FXT-002 and FXT-003 with enhanced pharmacokinetic and safety profiles. These findings support the use of ferroptosis inhibitors as a therapeutic strategy in transplantation and other IRI-associated conditions.

Background & Aims: Liver transplantation (LT) for hepatocellular carcinoma (HCC) is performed worldwide, with 5-year survival rates of approximately 70%. However, post-transplant HCC recurrence occurs in 15-20% of recipients. We aimed to evaluate, for the first time, long-term recurrence-free survival in a large international cohort of patients undergoing LT for HCC using grafts treated with hypothermic oxygenated machine perfusion (HOPE). Methods: This observational post hoc analysis of the multicenter European HOPE-REAL study (NCT05520320) included adult recipients with HCC (N = 599) who received a liver from either a donation after brain death (DBD) or donation after circulatory death (DCD) donor, preserved using HOPE, dual-HOPE (DHOPE), or normothermic regional perfusion followed by HOPE (NRP-HOPE) between 2012 and 2022. Propensity score matching was used to compare outcomes between HCC and non-HCC recipients within the HOPE-REAL cohort, and between HOPE-treated HCC recipients and an external control cohort receiving non-perfused livers (n = 484). Results: The overall HCC recurrence rate in the HOPE-REAL cohort was 6.9% (41/599), with no significant difference between DBD and DCD liver transplants (7.1% [25/350] vs. 6.4% [16/249]; p = 0.346). One-, 3-, and 5-year overall survival rates were 92%, 86%, and 81%, while recurrence-free survival rates were 90%, 83%, and 78%, respectively. Five-year overall survival was similar between 347 HOPE-treated HCC recipients (82%) and 347 matched non-HCC recipients (84%) (p = 0.625). In contrast, compared to an external cohort of 312 non-perfused HCC recipients, 5-year overall survival was significantly higher in 312 matched HOPE-treated HCC recipients (74% vs. 84%; p = 0.034). Conclusions: HCC recurrence was rare after transplantation of livers treated with HOPE. Long-term survival in HOPE-treated HCC recipients was significantly better than in those receiving non-perfused livers, and comparable to outcomes in non-HCC recipients. These findings warrant validation in a randomized clinical trial. Impact and implications: This post hoc analysis of the HOPE REAL study demonstrates, for the first time, low hepatocellular carcinoma (HCC) recurrence rates in a large cohort of hypothermic oxygenated machine perfusion-treated liver transplant recipients with HCC, and significantly better survival outcomes compared to matched recipients of non-perfused grafts. These findings may have important implications, particularly as tumor-related indications for liver transplantation continue to rise. Machine liver perfusion could emerge as a novel strategy to improve oncological outcomes in high-risk cancer conditions after transplantation, potentially via mitigation of inflammation and reduced tumor cell seeding. Clinical trial number: NCT05520320

PURPOSE OF REVIEW:Solid organ transplantation is life-saving but imposes substantial physical and psychological demands across the pre, peri-, and posttransplant trajectory. Emerging evidence highlights the potential of prehabilitation and rehabilitation to enhance resilience before surgery, support recovery afterward, and reduce surgical and medical complications, ultimately improving long-term health after transplantation. Despite growing evidence of their benefits, these strategies remain underutilized in transplant care. This review aims to introduce multimodal continuum of care that integrates prehabilitation and rehabilitation into a unified pathway before and after transplantation to optimize outcomes in solid organ transplantation. RECENT FINDINGS:Multimodal programs combining exercise, nutrition, and psychosocial support have demonstrated reductions in complications, shorter hospital stays, and improved survival and quality of life in surgical populations, with emerging evidence in transplantation. Consensus statements advocate individualized, adaptive interventions across the transplant continuum, delivered by interdisciplinary teams. Leveraging the same multidisciplinary team before and after transplantation fosters consistency, efficiency, and patient engagement-critical for adherence and empowerment. SUMMARY:Although high-quality transplant-specific evidence remains limited, targeted, multimodal prehabilitation and rehabilitation represent promising strategies to enhance functional capacity and long-term health. We therefore propose "better in, better out" as a guiding principle for transplant care, calling for its adoption as a new standard supported by emerging evidence across kidney, liver, lung, and heart transplantation.