Berzigotti, Annalisa

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.

Cirrhosis is a prevalent condition affecting more than 100 million people globally and carrying significant morbidity and mortality related to the development of portal hypertension and hepatic decompensation. Current treatment is primarily targeted at identifying chronic liver disease early and preventing the progression of fibrosis by treating the underlying etiology of liver disease. Treatment options for patients with advanced fibrosis are limited, and the only drug class approved for the prevention of hepatic decompensation remains nonselective beta-blockers. There are several pharmacological therapies being developed in both preclinical and clinical trials to explore their efficacy in preventing first hepatic decompensation. Most studies evaluate primary endpoints reflective of disease severity and portal hypertension, such as changes in HVPG or fibrosis stage based on histology or imaging. While many drugs are being investigated, much work is still needed to identify treatment targets with effective outcomes to move the needle in the field of cirrhosis management. This narrative review will address the current state of cirrhosis therapies, including potential new therapeutic targets, and provide direction on future advancements that will improve our current treatment paradigm and lead to better outcomes for those burdened with cirrhosis.

AbstractThe burden of obesity and metabolic syndrome has determined a sharp increase in bariatric surgery (BS) procedures, which lead to marked weight loss, improved metabolic syndrome, reduced cardiovascular risk, and even improvement in nonalcoholic steatohepatitis (NASH). Despite these promising results, BS in patients with chronic liver disease can rarely lead to worsening of liver function, progression to cirrhosis and its complications, and even liver transplantation. On the other hand, since obesity in patients with cirrhosis is a major cofactor for progression to a decompensated stage of the disease and a risk factor for hepatocellular carcinoma, BS has been used to achieve weight loss in this population. In this review, we critically analyze the existing data on outcomes of BS in patients with cirrhosis and the possible mechanisms leading to fibrosis progression and worsening liver function in patients undergoing BS. Finally, we propose a set of measures that could be taken to improve the multidisciplinary management of liver disease in patients undergoing BS, including early recognition of malnutrition and alcohol misuse.