MicroRNAs in Alcohol-Associated Liver Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease: From Pathogenic Networks and Disease Progression to Precision Biomarkers and Therapeutic Strategies

Alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD) arise from distinct etiological factors, but they share a broad spectrum of pathological features during disease progression, including steatosis, oxidative stress, autophagic dysfunction, inflammation, hepatocyte death, and fibrosis. MicroRNAs (miRNAs) are considered important potential post-transcriptional regulators of these processes because of their capacity to coordinately modulate multiple target genes and signaling pathways across diverse hepatic cell populations. In this review, the involvement of miRNAs throughout the progression of ALD and MASLD is comparatively examined, with particular emphasis on their roles in lipid metabolic dysregulation, mitochondrial and oxidative stress, autophagic dysfunction, immune activation, hepatocyte death, and hepatic-stellate-cell-associated fibrogenesis. This review focuses on the role of miRNAs in intercellular communication between hepatocytes, macrophages, neutrophils, and hepatic stellate cells, emphasizing their cell-specific and context-dependent functions in coordinating liver disease progression. Apart from their mechanistic roles, circulating and extracellular-vesicle-associated miRNA signatures have shown great application potential as minimally invasive biomarkers for molecular stratification, disease progression, and precision medicine. Collectively, these findings suggest that miRNAs have broad translational relevance in liver disease. However, their clinical translation remains limited by challenges regarding stability, biodistribution, off-target effects, and cell-type-specific delivery, emphasizing the need for more precise liver-directed therapeutic strategies. These challenges highlight the importance of linking specific miRNA targets with disease stage, cellular source, and appropriate delivery approaches. In this context, the integration of disease etiology, pathological stage, cellular context, miRNA network architecture, biomarker signatures, and delivery technology is essential for evolving miRNAs from mechanistic regulators and biomarkers into precision therapeutic platforms for ALD and MASLD.