Obesity and Metabolic Dysfunction‐Associated Steatotic Liver Disease ( <scp>MASLD</scp> ): A Literature Review on Pathophysiology and Treatment

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a key hepatic manifestation of obesity and systemic metabolic dysfunction and is a leading cause of chronic liver disease worldwide. Obesity-driven mechanisms, including adipose tissue dysfunction, insulin resistance and increased free fatty acid flux to the liver, promote ectopic lipid accumulation and lipotoxic injury. These processes trigger mitochondrial and endoplasmic reticulum stress, inflammation, immune activation and disturbances in the gut-liver axis, driving disease progression from simple steatosis to metabolic dysfunction-associated steatohepatitis, fibrosis and cirrhosis. MASLD is a highly heterogeneous condition, with differences in fat distribution, body composition and genetic susceptibility giving rise to distinct clinical phenotypes, including lean and non-lean MASLD, which have important implications for disease risk, progression and therapeutic response. Clinical outcomes are determined primarily by fibrosis stage, which represents the strongest predictor of liver-related and all-cause mortality, underscoring the importance of early disease recognition and risk stratification. Therapeutic strategies, therefore, increasingly target upstream metabolic drivers rather than hepatic steatosis alone. Lifestyle interventions remain foundational but are often limited by challenges in long-term adherence. Pharmacologic therapies, particularly incretin-based agents such as glucagon-like peptide-1 receptor agonists and dual incretin agonists, as well as bariatric and endoscopic metabolic procedures, have demonstrated substantial metabolic and hepatic benefits. Recognition of disease heterogeneity supports phenotype-guided approaches that integrate metabolic risk, adiposity, body composition and fibrosis assessment to personalise treatment strategies and improve long-term outcomes across the MASLD spectrum.