Exploring the Pathophysiological Mechanisms of Non-Alcoholic Fatty Liver Disease and Therapeutic Innovations

Abstract

Non-alcoholic fatty liver disease (NAFLD) represents a growing global health burden, characterized by excessive fat accumulation in hepatocytes without significant alcohol consumption. It encompasses a spectrum ranging from simple steatosis to the more severe non-alcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma. This paper delves into the multifactorial pathophysiology underlying NAFLD, including insulin resistance, lipotoxicity, mitochondrial dysfunction, and chronic inflammation, which synergistically contribute to disease progression. Additionally, we discuss the role of genetic predisposition and gut-liver axis dysregulation in exacerbating disease severity. Despite its prevalence, NAFLD currently lacks approved pharmacological treatments, relying primarily on lifestyle modifications. However, recent advances in understanding its molecular mechanisms have catalyzed the development of novel therapeutic strategies, including drugs targeting metabolic pathways, anti-inflammatory agents, and interventions aimed at restoring gut microbiota balance. This review synthesizes current knowledge on the pathophysiological mechanisms of NAFLD and highlights emerging therapeutic innovations, emphasizing their potential to transform clinical management. By exploring these aspects, this paper aims to contribute to the ongoing discourse on combating this pervasive and multifaceted disease.