Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Facts and Hopes

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a newly defined clinical condition characterized by hepatic steatosis in the presence of one or more cardiometabolic risk factors (CMRFs), such as obesity, type 2 diabetes, or dyslipidemia. It affects approximately 38% of the global population and is projected to increase to 55% by 2040, with higher prevalence among obese and diabetic individuals. MASLD has become a leading cause of cirrhosis and hepatocellular carcinoma (HCC) and is recognized as both a hepatic and systemic disease due to its association with cardiovascular, renal, and endocrine comorbidities. Despite growing epidemiological and clinical significance, MASLD remains underdiagnosed. Its management requires a structured, multidisciplinary approach. Several noninvasive tools have been developed to aid diagnosis and staging, though clinical limitations persist. Among prognostic factors, fibrosis stage remains the most reliable predictor of outcomes, including mortality. Effective care demands individualized, patient-centric pathways and regional adaptations of health interventions. Lifestyle modification remains the cornerstone of treatment, while pharmacological options are tailored to disease stage, phenotype, and comorbidities. Notably, resmetirom and semaglutide are the first Food and Drug Administration-approved hepatic disease-modifying agents for patients with moderate to advanced fibrosis. This review aims to provide a critical synthesis of recent advances in MASLD management, highlight therapeutic pathways, address gaps in current practice, and discuss health system priorities and research needs.