Roles of Extracellular Vesicle-Derived microRNAs in Metabolic Dysfunction-Associated Steatotic Liver Disease to Hepatocellular Carcinoma

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, and has emerged as a common etiological factor for hepatocellular carcinoma (HCC). MASLD and MASLD-associated HCC lack specific clinical biomarkers. Extracellular vesicles (EVs) and their microRNA (miRNA) cargo have emerged as key mediators of intercellular communication and promising diagnostic tools. This review provides a systematic overview of the stage-specific roles of EV-derived miRNAs across the MASLD spectrum. We focus on how key EV-miRNAs regulate lipid metabolism, inflammatory responses, hepatic stellate cell (HSC) activation, and the remodeling of the tumor microenvironment (TME). This review provides an updated perspective on cross-stage EV-derived miRNA regulatory circuits. In addition, we critically evaluate the potential of EV-derived miRNAs as non-invasive biomarkers and therapeutic targets. By integrating mechanistic insights with clinical relevance, this review provides a comprehensive framework for the early identification, risk stratification, and precision intervention of MASLD-associated HCC.