Pathological Evolution and Internal Medicine Management of Nonalcoholic Fatty Liver Disease (NAFLD) in the Era of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is now recognized as the most prevalent chronic liver disease worldwide, driven by the rise in obesity, type 2 diabetes, and metabolic syndrome. The evolving nomenclature and understanding of MASLD necessitate updated insights into its pathophysiology, diagnostics, and internal medicine management. A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Cochrane databases for articles published between 2018 and 2025. Eligible studies included human-based clinical or translational research addressing MASLD pathogenesis, diagnostics, and management. Non-invasive scoring systems, pharmacotherapies, and multidisciplinary management strategies were evaluated. The pathological progression of MASLD spans from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Key pathogenic mechanisms involve insulin resistance, adipokine imbalance, gut-liver axis dysregulation, and genetic polymorphisms such as PNPLA3. Diagnostic approaches have shifted toward non-invasive tools, including Fibrosis-4 (FIB-4), NAFLD Fibrosis Score, Enhanced Liver Fibrosis (ELF) score, Vibration-Controlled Transient Elastography (VCTE), and magnetic resonance imaging-proton density fat fraction (MRI-PDFF). Lifestyle modification remains the cornerstone of management, but promising pharmacologic therapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists, vitamin E, pioglitazone, and resmetirom, are emerging. Multidisciplinary risk factor control, including diabetes, lipid, and blood pressure management, is critical. Emerging biomarkers and multi-omics technologies, alongside artificial intelligence, are redefining MASLD stratification and therapeutic monitoring. Early identification and comprehensive management of MASLD are essential to prevent advanced liver disease and associated comorbidities. With evolving nomenclature, non-invasive diagnostics, and emerging therapies, internal medicine practitioners must adopt an integrative, multidisciplinary approach to care. Future research should prioritize personalized treatment strategies and health system integration to address the growing MASLD burden.