Background: Noninvasive tests are well validated in metabolic dysfunction–associated steatotic liver disease, but evidence in metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD) is limited. We evaluated noninvasive test–based clinical care pathways for fibrosis risk stratification in MetALD and ALD. Methods: This is a multinational, multicenter, cross-sectional study across 35 centers in 16 countries (2013–2025), including adults with MetALD or ALD. Fibrosis was assessed by liver biopsy and/or vibration-controlled transient elastography (VCTE). In biopsy-proven participants, we analyzed the sequential pathway (Fibrosis-4 [FIB-4] first, followed by VCTE for indeterminate FIB-4) to identify advanced fibrosis (≥F3). Diagnostic accuracy was assessed using the AUC. Results: Among 893 participants (41.3% MetALD and 58.7% ALD), the median age was 52 [43.0–61.0] years, and 79.4% were male. The estimated prevalence of advanced fibrosis was 45% (32.2% in MetALD and 54.0% in ALD). Participants with MetALD had a more dysmetabolic profile but lower fibrosis stages than ALD. Among biopsy-proven participants, FIB-4 AUC was 0.720, and VCTE AUC was 0.833. FIB-4 performed better in MetALD than ALD (AUC 0.773 vs. 0.540), while VCTE accuracy was similar across groups. In the sequential pathways, the false-negative rate for advanced fibrosis (misclassified as low risk) was 6.8% (4.9% MetALD and 11.3% ALD). Conclusions: In biopsy-proven patients, FIB-4 performance was acceptable in MetALD but substantially weaker in ALD. The standard 2-step pathway performed adequately in MetALD but missed a clinically meaningful proportion of advanced fibrosis in ALD.
Safety, tolerability, and efficacy of GLP-1 receptor agonists (GLP-1 RA) in the management of post–liver transplant weight gain: A multicenter, observational study
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.
Proceedings of the 30th Annual Congress of the International Liver Transplantation Society
The 2025 Annual Congress of the International Liver Transplantation Society (ILTS), themed “ Advancing Liver Transplantation: Embracing Innovation for the Future ,” was held from May 28 to 31 in Singapore. The meeting offered a comprehensive scientific program, featuring 92 sessions and 7 pre-congress workshops spanning living donor liver transplantation, advanced surgery, anesthesia and critical care, transplant oncology and immunology, basic science, pediatrics, and more. The program emphasized collaboration and innovation to advance patient outcomes in liver transplantation. In this report, the ILTS Vanguard Committee summarizes the key proceedings of the congress.
Development of posttransplant diabetes mellitus in US recipients of liver transplant is influenced by OPTN region
Posttransplant diabetes mellitus (PTDM) is associated with significant morbidity and mortality in liver transplant recipients (LTRs). We used the Organ Procurement and Transplantation Network (OPTN) database to compare the incidence of developing PTDM across the United States and develop a risk prediction model for new-onset PTDM using OPTN region as well as donor-related, recipient-related, and transplant-related factors. All US adult, primary, deceased donor, LTRs between January 1, 2007, and December 31, 2016, with no prior history of diabetes noted, were identified. Kaplan-Meier estimators were used to calculate the cumulative incidence of PTDM, stratified by OPTN region. Multivariable Cox proportional hazards models were fitted to estimate hazards of PTDM in each OPTN region and build a risk prediction model, through backward selection. Cumulative incidence of PTDM at 1 year, 3 years, and 5 years after transplant was 12.0%, 16.1%, and 18.9%, respectively. Region 3, followed by regions 8, 2, and 9, had the highest adjusted hazards of developing PTDM. Inclusion of OPTN region in a risk prediction model for PTDM in LTRs (including recipient age, sex, race, education, insurance coverage, body mass index, primary liver disease, cold ischemia time, and donor history of diabetes) modestly improved performance (C-statistic = 0.60). In patients without pre-existing, confirmed diabetes mellitus, the incidence of PTDM in LTRs varied across OPTN regions, with the highest hazards in region 3, followed by regions 8, 2, and 9. The performance of a novel risk prediction model for PTDM in LTRs has improved performance with the inclusion of the OPTN region. Vigilance is recommended to centers in high-risk regions to identify PTDM and mitigate its development.
Proceedings of the 28th Annual Congress of the International Liver Transplantation Society
The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on “Liver Disorders and Transplantation: Innovations and Evolving Indications.” This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.
Reply: More on nonalcoholic/nonmetabolic dysfunction–associated steatohepatitis
Cardiovascular disease (CVD) is a leading complication after liver transplantation and has a significant impact on patients’ outcomes posttransplant. The major risk factors for post–liver transplant CVD are age, preexisting CVD, nonalcoholic fatty liver disease, chronic kidney disease, and metabolic syndrome. This review explores the contemporary strategies and approaches to minimizing cardiometabolic disease burden in liver transplant recipients. We highlight areas for potential intervention to reduce the mortality of patients with metabolic syndrome and CVD after liver transplantation.
Navigating the “specific etiology” steatohepatitis category: Evaluation and management of nonalcohol/nonmetabolic dysfunction–associated steatohepatitis
Obesity is highly prevalent in hepatology clinics and has a significant impact on chronic liver disease and patient management. Hepatologists and gastroenterologists need to be actively engaged in the management of obesity. This review provides a detailed approach to this challenging comorbidity.
Changing Landscape of Liver Transplantation in the Post-DAA and Contemporary ART Era
Combination anti-retroviral therapy has drastically improved solid organ transplantation outcomes in persons living with HIV. DAA therapy has led to the successful eradication of HCV. While recent data have suggested improvement in outcomes in HIV/HCV-coinfected liver transplant recipients, temporal trends in patient survival within pre- and post-DAA eras are yet to be elucidated. The UNOS database was utilized to identify deceased donor liver transplant recipients between 1 January 2000 and 30 September 2020 and stratify them by HIV and HCV infection status. A total of 85,730 patients met the inclusion criteria. One-year and five-year patient survival improved (93% and 80%, respectively) for all transplants performed post-2015. For HIV/HCV-coinfected recipients, survival improved significantly from 78% (pre-2015) to 92% (post-2015). Multivariate regression analyses identified advanced recipient age, Black race, diabetes mellitus and decompensated cirrhosis as risk factors associated with higher one-year mortality. Liver transplant outcomes in HIV/HCV-coinfected liver transplant recipients have significantly improved over the last quinquennium in the setting of the highly effective combination of ART and DAA therapy. The presence of HIV, HCV, HIV/HCV-coinfection and active HCV viremia at the time of transplant do not cause higher mortality risk in liver transplant recipients in the current era.