Metabolic Dysfunction-Associated Steatotic Liver Disease and Obesity: Pathogenesis, Diagnostics, Risk Stratification, and Therapeutic Approach

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disease worldwide, closely linked to the global rising incidence of obesity and metabolic syndrome. This review synthesizes current evidence on the pathogenesis, gut-liver axis, and multidisciplinary management of MASLD within the context of obesity. The pathophysiology of MASLD is multifactorial and involves insulin resistance, adipose tissue dysfunction, chronic low-grade inflammation, and alterations in lipid metabolism, all of which contribute to hepatic steatosis and disease progression. Recent research has increasingly focused on the gut-liver axis, where dysbiosis, increased intestinal permeability, endotoxemia, and microbial metabolites significantly influence hepatic inflammation and fibrogenesis. From a therapeutic perspective, lifestyle modifications remain foundational to management; however, their long-term sustainability is often limited. Pharmacologic interventions targeting metabolic pathways, such as incretin-based therapies, demonstrate promising efficacy in enhancing both hepatic and systemic outcomes. Given the substantial clinical and socioeconomic burden posed by MASLD, a multidisciplinary approach that integrates perspectives from hepatology, endocrinology, nutrition, and public health is essential. Future research should prioritize personalized risk assessment, early intervention in high-risk populations, and policy-level strategies to mitigate the growing impact of metabolic liver disease.