THE EVOLVING LANDSCAPE OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE: FROM PATHOGENESIS TO PRECISION MEDICINE

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD), recently reclassified as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), represents one of the most significant challenges in modern hepatology and metabolic medicine (Rinella et al., 2023). This paper examines the evolution of the disease's nomenclature and pathophysiological concepts, emphasizing its direct link to the global epidemic of obesity, type 2 diabetes, and metabolic syndrome (Younossi et al., 2016). The review details the multifactorial pathogenesis of the disease, addressing the roles of insulin resistance, oxidative stress, gut dysbiosis, and genetic predispositions (including variants in the PNPLA3 and TM6SF2 genes) (Eslam et al., 2022; Kozlitina et al., 2014). It provides a comprehensive overview of contemporary diagnostic methods, ranging from the traditional "gold standard" of liver biopsy to advanced imaging techniques such as elastography and MRI-PDFF, alongside non-invasive biomarkers (EASL, 2021; Vilar-Gomez et al., 2024). Furthermore, the paper compares the significance of lifestyle modifications with the rapidly evolving landscape of pharmacotherapy, including GLP-1 receptor agonists (Newsome et al., 2021). A primary focus is placed on the potential of precision medicine; the integration of genetic profiling, artificial intelligence, and machine learning offers new avenues for risk stratification and the personalization of therapy (Plompen et al., 2023). The paper concludes by addressing diagnostic limitations and identifying future research priorities aimed at optimizing patient care for MASLD in the era of personalized medicine.