Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies.

Metabolic-dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a highly prevalent metabolic disorder characterized by hepatic steatosis in conjunction with at least one cardiometabolic risk factor, such as obesity, type 2 diabetes, hypertension, or dyslipidemia. As global rates of obesity and metabolic syndrome continue to rise, MASLD is becoming a major public health concern, with projections indicating a substantial increase in prevalence over the coming decades. The disease spectrum ranges from simple steatosis to metabolic-dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma, contributing to significant morbidity and mortality worldwide. This review delves into the molecular mechanisms driving MASLD pathogenesis, including dysregulation of lipid metabolism, chronic inflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota alterations. Recent advances in research have highlighted the role of genetic and epigenetic factors in disease progression, as well as novel therapeutic targets such as peroxisome proliferator-activated receptors (PPARs), fibroblast growth factors, and thyroid hormone receptor beta agonists. Given the multifaceted nature of MASLD, a multidisciplinary approach integrating early diagnosis, molecular insights, lifestyle interventions, and personalized therapies is critical. This review underscores the urgent need for continued research into innovative treatment strategies and precision medicine approaches to halt MASLD progression and improve patient outcomes.