MASLD: Established Knowledge and Emerging Directions - Guideline Updates

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health challenge, largely driven by the increasing prevalence of obesity and type 2 diabetes mellitus. The disease spectrum ranges from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with progressive fibrosis. Advanced fibrosis substantially increases the risk of cirrhosis, hepatocellular carcinoma, and cardiovascular complications, thereby contributing significantly to morbidity and mortality.Although lifestyle modification remains the cornerstone of therapy, pharmacological treatment is gaining importance in patients with progressive disease or high-risk profiles. Advances in the understanding of MASLD pathophysiology have enabled the development of targeted therapies addressing hepatic lipid accumulation, insulin resistance, inflammation, and fibrogenesis. Promising clinical data have been reported for resmetirom, semaglutide, tirzepatide, survodutide, lanifibranor, and fibroblast growth factor-21 analogues including efruxifermin, pegozafermin, and efimosfermin.This review summarises current and emerging diagnostic and therapeutic strategies and provides practical guidance for clinical management. In addition, a structured treatment algorithm for non-cirrhotic MASLD (F0-F3), restricted to therapies currently available in Europe and stratified according to diabetes status and fibrosis stage, is proposed as an evidence-based tool for routine clinical practice.