AISF practice guidance on pharmacological treatment of metabolic-dysfunction associated steatotic liver disease and steatohepatitis (MASLD/MASH): A 2026 Update.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has rapidly emerged as the leading cause of chronic liver disease worldwide, gradually replacing viral hepatitis in clinical and epidemiological relevance. Italian data mirror global trends, with prevalence escalating in general and high-risk populations, particularly among individuals with type 2 diabetes (T2D), obesity, and metabolic syndrome (MetS). Disease progression from steatosis to steatohepatitis (MASH) and advanced fibrosis markedly increases the risk of cirrhosis, hepatocellular carcinoma (HCC), and cardiovascular mortality. Recent regulatory frameworks from FDA and EMA have accelerated therapeutic development, with Resmetirom and Semaglutide representing the first agents to achieve histological efficacy in Phase 3 trials for patients with MASH and F2-F3 fibrosis. Building upon these advances, the AISF STEPS-MASH framework provides a structured approach for the identification, selection, and monitoring of patients eligible for therapy. This position paper outlines evidence-based recommendations for the integration of emerging pharmacological strategies into clinical practice in Italy, emphasizing both high-risk and broader metabolic populations.