Different Cell Death Mechanisms of Non-alcoholic Fatty Liver Disease (NAFLD) and the Dawn of Targeted Therapy

According to recent epidemiological studies, the incidence of non-alcoholic fatty liver disease (NAFLD) has significantly increased globally, with estimates indicating that more than 25% of the world's population is impacted. Because of its close ties to obesity and metabolic dysfunction, NAFLD has become the most prevalent chronic liver disease in Western societies, even reaching epidemic proportions. The pathogenesis of NAFLD is closely associated with diverse modes of hepatocyte demise, which collectively drive inflammatory responses, fibrotic processes, and eventual hepatic functional impairment. The most well-researched of these mechanismsapoptosis, necroptosis, pyroptosis, and ferroptosisall have unique roles in the pathophysiology of NAFLD. Therefore, inhibiting cell death is a possible solution for NAFLD. This paper first discusses the pathophysiological mechanisms of NAFLD, and then discusses the mechanisms of four different existing cell death modes, particular cell death responses and molecular patterns in the onset of liver disease. The possibility of different cell death pathways as therapeutic targets is then discussed. In conclusion, this review synthesizes current knowledge on the contributions of distinct cell death mechanisms to NAFLD pathogenesis and explores their therapeutic potential by linking targeted treatment strategies to specific cell death pathways, thereby identifying novel opportunities for clinical intervention.