The Role of Neutrophils in Non-Alcoholic Fatty Liver Disease: Mechanisms and Clinical Significance.

This review methodically elucidates the pivotal role of neutrophils in the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD). A body of research indicates that neutrophils are preactivated in a background of systemic metabolic dysregulation. Furthermore, neutrophils are specifically recruited to the liver via the CXCR2/CXCL1 axis. In the liver microenvironment, neutrophils directly mediate hepatocyte injury and potently amplify inflammation through synergistic mechanisms. These mechanisms include degranulation, the release of toxic proteases, the production of reactive oxygen species, and the formation of neutrophil extracellular traps. More crucially, neutrophils have been shown to promote disease progression from simple fatty liver to non-alcoholic steatohepatitis, liver fibrosis, and hepatocellular carcinoma by forming complex interaction networks with macrophages, hepatic stellate cells, and hepatocytes. These findings not only deepen our understanding of the immunopathological mechanisms of NAFLD but also highlight the immense clinical translational potential of neutrophils as novel biomarkers and therapeutic targets.