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Post–liver transplant (LT) weight gain and metabolic dysfunction predispose to cardiovascular (CV) morbidity, allograft steatosis, and reduced long-term survival. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) promote weight loss and improve cardiometabolic health, yet evidence in liver transplant recipients (LTRs) is limited. We aimed to evaluate the safety, tolerability, and efficacy of GLP-1 RAs in post-LT weight management. We performed a multicenter retrospective cohort study of adult LTRs treated with GLP-1 RAs across 4 international centers (January 1, 2010–June 30, 2025). Regular GLP-1 RA users were compared with matched non-users by age, sex, obesity, and diabetes status, transplant year, and center. The primary outcome was the change in body weight 1-year post-exposure. Secondary outcomes included glycemic and lipid profiles, kidney and allograft function, immunosuppression effects, major adverse cardiovascular events (MACE), and adverse effects. Longitudinal analyses used linear mixed models with multiple imputation. Among 104 GLP-1 RA users, 68.3% initiated therapy for diabetes; subcutaneous semaglutide was most used at a median dose of 0.82±0.46 mg weekly. Treatment led to significant reductions in body weight (−3.8 kg; −3.9%, p <0.001), body mass index (BMI) (−1.6 kg/m 2 ; −5.0%, p <0.001), and glycated hemoglobin (HbA1c) (−0.48%, p =0.002), with modest lipid improvement. Liver function tests and immunosuppression trough levels remained stable, and no treatment-limiting adverse events occurred. In matched analyses (80 GLP-1 RA users vs. 116 non-users), GLP-1 RAs facilitated greater weight loss (−3.4 kg difference, p =0.009) and HbA1c reduction (−0.43% difference in HbA1c, p =0.042) without increased risk of allograft dysfunction, T-cell–mediated rejection (TCMR), or MACE. This multicenter, international study demonstrates GLP-1 RAs are safe and moderately effective in reducing weight and improving metabolic parameters post-LT, without adverse effects on allograft function or immunosuppression, despite limitations of low dosing. Prospective, randomized trials of GLP-1 RAs in LTRs are thus warranted.

Living liver donation is a critical component for addressing organ shortage and improving outcomes for patients with end-stage liver disease. As the prevalence of living donor liver transplantation (LDLT) increases worldwide, understanding and optimizing long-term donor health is paramount. The 2025 International Liver Transplantation Society and International Living Donor Liver Transplantation Society (ILTS-iLDLT) Consensus Conference convened experts in the field of liver transplantation to establish evidence-based guidelines focused on the long-term medical, psychological, and social considerations following living liver donation. The aim of this working group was to integrate current evidence and expert consensus on donor follow-up protocols, risk assessment, and management strategies to promote long-term donor health, quality of life, and living liver donor programs globally to safeguard the welfare of this unique population.

Background. As cancer therapeutics improve, more liver transplant (LT) candidates will have a history of prior to transplant malignancy (PTM), an established risk for cancer posttransplant. Methods. This study provides granular analysis (with focus on nonliver PTM) of posttransplant cancer risk relating to PTM in 1105 consecutive adult LT recipients (2009–2019, N = 542 with PTM). Results. PTM prevalence increased from 37.8% to 63.2% during this timeframe. Post-LT survival was lower (10 y: 61.2% versus 75.1%; P < 0.001) with higher cancer-related mortality (17.6% versus 2.2%; P < 0.001) in patients with any PTM. The higher cumulative incidence of cancer post-LT associated with PTM (59.7% versus 37.6%; P < 0.001) was not attributable to de novo cancer (38.5% versus 37.7%; P = 0.21) but to recurrence. Cancer recurrence rate (10 y) was lowest in nonliver/nonskin (“other”) PTM (10.6%) with mortality rates from recurrence of only 4% in this cohort. De novo cancers may present at more advanced stage in patients with PTM and lung cancer the most common nonskin de novo malignancy (PTM 21%, no PTM 7%). Family history of cancer was an independent predictor for de novo cancer. Conclusions. PTM associated post-LT cancer outcomes are dominated by skin and liver cancer recurrence and not recurrence of “other” cancers or de novo cancer. This data supports the guidance proposals for cautious liberalization of “other” cancer remission requirements before transplantation. As post-LT cancer is highly prevalent regardless of PTM status, adherence to posttransplant cancer screening and surveillance is critical to identify early cancer after transplant.

Background. Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized as a significant indication for liver transplantation (LT) in North America. Yet data on its impact in other countries, such as Spain, remain limited. This study aimed to evaluate the prevalence and trajectory of MASLD-related LT in Spain and compare these findings with broader national data and international data sets. Methods. Multicenter retrospective cohort study including adults (18 y and older) undergoing LT for MASLD between 2010 and 2023 in 5 large Spanish centers. Additional data were obtained from the Spanish Transplant Registry (Organización Nacional de Trasplantes) and high-prevalence LT centers in the United States (n = 7) and Canada (n = 1). Results. Among 3448 LTs performed in the 5 Spanish centers, 3.4% (n = 117) were MASLD-related. An increasing trajectory of MASLD-related LT was observed, with predictions suggesting a rise to 5.4%–10.8% of LTs for MASLD by 2028. These trends were consistent with Organización Nacional de Trasplantes data. Compared with North American data, the growth trajectory in Spain showed a less steep increase. Hepatocellular carcinoma rates were higher in the Spanish MASLD-LT recipients, yet metabolic comorbidities were frequent in all populations. Conclusions. The burden of MASLD-related LT in Spain is growing, yet at a less pronounced rate than in the United States/Canada. Whether this slower increase will persist or decline in the future as newer antiobesity and MASLD-related drugs are increasingly used is still unknown. In the meantime, our results highlight the need for tailored approaches to management and prevention in the Spanish population and underscore the importance of continued monitoring and research into the evolving impact of MASLD on LT in Spain and beyond.

Immune checkpoint inhibitors (ICIs) have improved cancer prognosis significantly, but their use has been avoided in liver transplant recipients (LTr) due to poorly characterized rejection risk. Data surrounding rejection risk are extremely suboptimal, with highly variable immunosuppression approaches and follow-up, and do not account for the learning curve in managing immunosuppression in the setting of ICI. A standardized institutional clinical practice protocol was developed in 2021 for immunosuppression management to facilitate ICI therapy with prospective close follow-up for immunosuppression levels and allograft function. Of 20 LTr, 12 (60%) were male, 18 (90%) were Caucasian, with a mean age of 54.0 (SD 11.2) years. However, 13/20 had 2 or more failed cancer therapies before ICI. Hepatocellular carcinoma ​(HCC) (N=7), lung (N=3), and melanoma (N=3) were the most frequent. Time from first ICI treatment to death was <30 days (N=5), 30–59 days (N=4), 60–89 days (N=1), and >90 days (N=6). Most deaths were cancer-related, reflecting the late stage of disease. ICI toxicity occurred in 3 LTr; pneumonitis (N=1, 5%), myocarditis (N=1, 5%), and acute cellular rejection (N=1, 5%). Four patients remain alive 178–341 days with stable allograft function and slow reduction in immunosuppression. Three out of 4 patients have a partial cancer response, and 1 with slowed progression of disease. ICI treatment in the immunosuppressed LTr is feasible with careful immunosuppression management and follow-up. Demonstrating a low rejection risk should allow for earlier utilization of these agents to improve cancer prognosis. Optimizing rejection risk with cancer response requires ongoing study.

ABSTRACTIntroductionVaccination is crucial to the thoracic solid organ transplant (SOT) population to reduce vaccine‐preventable infection. However, data on posttransplant hepatitis B virus (HBV) vaccination compliance and vaccine‐induced seroprotection are lacking.MethodsWe conducted a retrospective study of adult thoracic organ (heart and lung) transplant recipients at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Recombivax HB was used before 2020, and Heplisav‐B was preferred after 2020. Recipients with posttransplant hepatitis B surface antibody (HBsAb) < 10 IU/L were eligible for the HBV vaccine. HBV seroprotection was defined as an HBsAb ≥ 10 IU/L.ResultsA total of 1116 recipients were evaluated, all of whom underwent posttransplant HBsAb testing. Of these, 751 (67%) had an HBsAb level < 10 IU/L and were eligible for posttransplant HBV vaccination. Of the eligible recipients, 117 (16%) completed the HBV vaccine series during the study period. Among these 117 recipients, 40 (34%) had their HBsAb levels rechecked after completing the vaccine series, with a seroprotection rate of 37.5% (15/40). There was no statistically significant difference in the seroprotection rates between Heplisav‐B and Recombivax HB vaccines (39% [13/33] vs. 29% [2/7]; p = 0.691). In addition, HBsAb levels were lowest at week 2 but rebounded at week 4 posttransplant and pretransplant HBsAb levels of ≥100 IU/L ensured 5‐year seroprotection.ConclusionSuboptimal compliance with HBV vaccination and poor vaccine‐induced seroprotection occur in thoracic organ transplant recipients, regardless of the vaccine used. These findings underscore the necessity of enhancing vaccination strategies for SOT recipients. image

614 Background: Liver transplantation (LT) offers a 5-year survival exceeding 70% for selected patients with hepatocellular carcinoma (HCC). Immune checkpoint inhibitors (ICIs) may be used to downstage or bridge to transplantation. This study aims to evaluate the safety of ICIs prior to LT. Methods: Multicenter retrospective study, involving 9 centers, included adults who received ICIs and, subsequent LT, between 2019 and 2023. The ICI cohort was matched by age, sex, liver diseases and transplant date (1:3) with a similar cohort of HCC transplanted patients that did not receive ICIs. Results: The ICI cohort included 45 patients (Table part 1). The most common underlying liver diseases were viral. 15.5% of patients had macrovascular invasion and, 62.2% multifocal disease. The most commonly used ICI was nivolumab (75.6%), followed by atezolizumab-bevacizumab (17.8%). The median follow up was 32.5 months (17.4 - 47.6). The median ICI duration was 147 days (129.5-276.5), with a median interval of 58 days (22–193) between the last ICI dose and LT. There were 8 (17.8%) cases of graft rejection, 2 steroid-resistant leading to 1 graft failure. There were 4 (8%) HCC recurrences. During follow-up there were 6 deaths, 2 related to HCC recurrence and 4 non liver related. When compared with 135 non-ICI cohort patients, there were no differences within the groups (Table part 2). Importantly, we found no significant differences in crude rejection rates (p=0.5). Conclusions: Our study suggest that ICI treatment prior to LT is safe. ICI rejection primarily occurs in the acute post-transplant period (within 3 months), with a low risk of death due to graft failure. Further clinical trials are needed. Part 1: ICI cohort descriptive analysis. N (%); Median (IQR); Part 2: Comparison between cohorts. N (%); Mean (SD). (part 1) ICI-cohort n=45 General data Male 38 (84.4) Age 61.2 (7.6) Etiology of liver diseases Hepatitis C 17 (37.8)Hepatitis B 6 (13.3)MASLD 6 (13.3)Viral +Alcohol 5 (11.1)Alcohol 3 (6.7)Autoimmune 3 (6.7)Other 3 (6.7)Combined viral 2 (4.4) Largest tumor (mm) 39 (22) Macrovascular invasion 7 (15.5) Multifocal 28 (62.2) Locoregional therapy 36 (80.0) Number of locoregional therapies 2 (2) Immunotherapy Nivolumab 34 (75.6) Atezolizumab/bevacizumab 8 (17.8) Pembrolizumab 1 (2.2) Nivolumab+pembrolizumab 1 (2.2) PD1 inhibitor clinical trial 1 (2.2) Days of ICI treatment 147 (203) Radiological tumor response ICI No 17 (37.8) Transplant Deceased donor 43 (95.6) Washout period (days) 58 (171) Induction therapy (anti-thymoglobulin) 8 (17.8) Outcomes Rejection Biopsy proven 8 (17.8) 8 (100) Time to rejection (days) 43 (102) Graft failure Rejection 2 (4.4)1 (2.2) HCC recurrence 4 (8) Deaths 6 (13.3) Follow up Since transplant (months) 32.5 (30.2) (part 2) ICI-cohort (n=45) Non-ICI cohort (n= 135) P Post transplant rejection rate 8 (17.8) 32 (23.7) 0.53 Time to rejection (days) 180.1 (SD 218) 62.2 (SD 62.8) 0.25 Overall deaths 6 (13.3) 10 (7.4) 0.36

Background: Diagnostic uncertainty caused by the low positive predictive value of HEV-specific IgM antibody (Ab) testing in a low-prevalence setting. We investigated the utility of a two-step HEV IgM Ab testing approach for diagnosing HEV infection. Methods: We retrospectively reviewed all adults who underwent HEV IgM Ab and/or HEV RNA testing from July 2013 through June 2023 at Mayo Clinic. Two-step HEV IgM testing involved initial testing using recomWell HEV IgM ELISA (Mikrogen, Neuried, Germany), with reflex to recomLine HEV IgM Strip (Mikrogen, Neuried, Germany) on all recomWell HEV IgM-reactive or IgM-equivocal specimens, as recomLine HEV IgM has higher specificity than recomWell HEV IgM but is more labor-intensive. Results: A total of 1640 patients had HEV IgM Ab or HEV RNA testing, including 1293 (79%) with only HEV IgM Ab testing, 213 (13%) with only HEV RNA testing, and 134 (8%) with both HEV IgM Ab and HEV RNA testing. Eighteen HEV infections were diagnosed with acute (N=16) and chronic (N=2) infections. Two-step IgM Ab testing did not identify 2 solid organ transplant recipients with chronic HEV infection. In acute HEV infection with HEV viremia, 3 out of 4 patients (2 solid organ transplant recipients and 1 patient with Guillain-Barre syndrome) were treated with ribavirin. Conclusions: A two-step HEV IgM Ab test may accurately diagnose acute HEV infection in immunocompetent persons. However, this approach fails to identify chronic HEV infection in immunocompromised individuals who need HEV RNA testing to establish the diagnosis.

Introduction: Portopulmonary hypertension (POPH) and associated pulmonary vascular resistance (PVR) elevation is seen in the context of underlying portal hypertension and liver disease. In the systemic circulation, liver cirrhosis can cause inappropriate splanchnic and systemic vasodilation with decreased systemic vascular resistance (SVR). Midodrine is used to maintain blood pressure in the setting of low SVR. Pulmonary vasodilators have systemic vasodilatory effects; the implications of combined midodrine and pulmonary vasodilator use in POPH are unanswered questions. Hypothesis: We hypothesized that SVR would decrease over time in patients with POPH started on pulmonary vasodilators, and that use of midodrine (as a surrogate for depressed SVR), may be associated with increased risk of mortality in patients with POPH starting pulmonary vasodilator therapy. Methods: Patients from the 3 Mayo Clinic sites (Rochester, MN; Jacksonville, FL; Scottsdale, AZ) diagnosed with POPH from 1988-2020 were included in the database. Patients met hemodynamic criteria for POPH via right heart catheterization (RHC). Hemodynamics were obtained from echocardiography and RHC at initial and subsequent visits. The hazard ratio for risk of death was estimated using Cox proportional hazards method. SVR was calculated using mean arterial pressure and cardiac output. Results: Analysis included 147 POPH patients, 34 (23%) on midodrine and 113 (77%) not requiring midodrine. There were 116 patients with longitudinal SVR data. The mean initial SVR was 1224 Dyne sec cm-5 and decreased 251 Dyne sec cm-5 [95% CI -337 to -165 251 Dyne sec cm-5, p<0.0001] with no difference between midodrine groups (p=0.57). Patients in the midodrine POPH group had an increased risk of mortality compared to those without midodrine use (HR 1.51, 95% CI: 1.02-2.21, p=0.0371). Conclusions: Patients with POPH starting pulmonary vasodilator have a reduction in SVR related to vasodilator therapy. Midodrine use with pulmonary vasodilator therapy is associated with increased mortality in the POPH population. Further study of the safety of combined midodrine and pulmonary vasodilator use in POPH is needed along with exploration of more selective pulmonary vasodilators.

With longer survival of patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation (LT), the frequency and risk factors associated with vascular and biliary complications in the allograft and the impact on long-term outcomes are poorly understood. To assess frequency and risk factors for long-term outcomes in patients after LT for PSC, all recipients of LT for advanced stage PSC for a non-cholangiocarcinoma indication from 1984 to 2012, with follow-up through March 2022 (>10+ y follow-up), were identified. One-, 5-, and 10-year cumulative risks of complications were estimated using the Aalen-Johansen method, where death was considered a competing risk. Two hundred ninety-three patients (mean age, 47.3 ± 12 y) formed our study cohort. One hundred and thirty-four patients received LT before 1995, and 159 were transplanted after 1995. Over a median (IQR) follow-up of 15.0 (10.3–22.1) years, LT was complicated by hepatic artery thrombosis (N = 30), portal vein stenosis/thrombosis (N = 48), biliary leak (N = 47), biliary strictures (N = 87), recurrent PSC (N=107), and graft failure (N=70). The 1-, 5-, 10-, and 15-year cumulative incidence of recurrent PSC was 1.0%, 8.0%, 23.5%, and 34.3%, respectively. The type of donor and older donor age were associated with an increased risk of biliary strictures. Donor age >60 years was associated with an increased risk of recurrent PSC. Long-term patient and graft survival have not changed significantly for patients transplanted for PSC. Controlling transplant-related factors, such as donor age, prompt identification of vascular and biliary complications early, and long-term rigorous follow-up, is recommended to continue to improve on these outcomes.