Challenges in the management of MetALD after liver transplantation

Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) are among the leading indications for liver transplantation (LT). The definition of metabolic dysfunction- and alcohol-associated liver disease (MetALD) identifies individuals with MASLD who consume moderate levels of alcohol, representing a severe phenotype within the steatotic liver disease (SLD) spectrum. Patients with MetALD face higher risks of post-LT complications, including metabolic syndrome, graft steatosis, and fibrosis. Despite the rising prevalence of MetALD due to increasing obesity and alcohol consumption, data on its recurrence or de novo development post-LT remain limited. The management of MetALD post-LT is particularly challenging due to the interplay of metabolic factors and potential alcohol relapse. Current evidence suggests that recurrent or de novo MetALD often progresses more rapidly to advanced fibrosis than in native livers, underscoring the importance of early detection and management. Integrated approaches addressing both metabolic syndrome and alcohol-related risks are essential for optimal management. Non-invasive diagnostic modalities, such as transient elastography and specific biomarkers like phosphatidylethanol (Peth), are promising in assessing graft health and alcohol relapse, respectively. Emerging therapies, including glucagon-like peptide-1 receptor agonists (GLP1-RAs) and fibroblast growth factor-21 (FGF21) analogs, offer potential dual-action benefits targeting metabolic dysfunction and alcohol consumption. These innovations, coupled with lifestyle interventions and tailored immunosuppressive regimens, may improve patient outcomes and reduce graft failure. This review highlights the need for multidisciplinary strategies and further research to optimize the management of MetALD post-LT, aiming to improve survival and quality of life in this high-risk population.