The transition from NAFLD to MASLD: implications for Diagnosis, Prognosis, and Clinical Management

The transition from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) reflects a paradigm shift in hepatology and highlights the need for a more pathophysiologically based classification. The aim of this review is to critically examine the conceptual evolution from NAFLD to MASLD, highlighting the implications for pathogenesis, diagnosis, risk stratification, and therapeutic strategies within the broader context of systemic metabolic dysfunction. Unlike the exclusion-based NAFLD definition, MASLD is grounded in positive diagnostic criteria and recognizes hepatic steatosis as a manifestation of metabolic disease. This reclassification improves clinical risk assessment and aligns hepatic care with cardiometabolic management. MASLD is closely linked to insulin resistance, lipotoxicity, chronic inflammation, and gut dysbiosis, which contribute to cardiovascular disease, chronic kidney disease, type 2 diabetes, and hepatocellular carcinoma. Non-invasive tools (e.g., FIB-4, elastography, ELF score) and emerging biomarkers (e.g., miR-122, CK-18, FGF21) support early diagnosis and personalized approaches. Therapeutically, MASLD management includes lifestyle modification, antidiabetic agents (GLP-1 receptor agonists, SGLT2 inhibitors), PPAR agonists, and novel drugs such as resmetirom. This evolving framework demands integrated, multidisciplinary strategies to address the systemic burden and clinical heterogeneity of MASLD.