Metabolic Dysfunction–Associated Steatotic Liver Disease: From Pathophysiology to Clinical Management

Abstract

Metabolic dysfunction–associated steatotic liver disease (MASLD) is currently one of the most prevalent chronic liver diseases worldwide, closely linked to the growing epidemics of obesity and type 2 diabetes. The pathogenesis of MASLD involves a complex interplay of metabolic, genetic, and environmental factors leading to excessive hepatic lipid accumulation, endoplasmic reticulum stress, inflammation, and progressive fibrosis. Central pathogenic mechanisms include insulin resistance, visceral obesity, atherogenic dyslipidemia, and activation of proinflammatory signaling pathways. Early diagnosis relies on the combination of metabolic risk assessment, laboratory markers (including TyG, HOMA-IR, liver enzymes, fibrosis indices), and non-invasive imaging methods such as ultrasound, elastography, and MRI. Recent international consensus has introduced a new terminology—MASLD and MASH—to better reflect the metabolic nature of the disease and remove stigmatizing elements associated with the former NAFLD/NASH terminology. Management strategies focus on weight reduction through lifestyle modification, optimal control of metabolic comorbidities, and emerging pharmacotherapies, including GLP-1 receptor agonists, SGLT2 inhibitors, and resmetirom. MASLD represents a major global health challenge, requiring interdisciplinary collaboration and early intervention to prevent advanced fibrosis, cirrhosis, and related cardiovascular complications.