Extracellular RNAs in Liquid Biopsy: Applications in MASLD and MASH Diagnosis and Monitoring

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition linked to obesity, diabetes, and metabolic syndrome, and can progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Current diagnostic standards such as liver biopsy are invasive and unsuitable for routine screening. Liquid biopsy, particularly through analysis of extracellular RNAs (exRNAs), including microRNAs (e.g., miR-122, miR-21, miR-34a), long non-coding RNAs, and tRNA-derived fragments, offers a promising non-invasive alternative. These exRNAs, released from hepatocytes and carried in blood via extracellular vesicles or protein complexes, can be detected using techniques like RNA sequencing, qRT-PCR, and droplet digital PCR. These biomarkers correlate with histologic severity, fibrosis stage, and treatment response, and have shown promising diagnostic utility; however, their performance may differ across various populations and disease stages. Despite their potential, clinical translation is limited by a lack of standardization and large-scale validation. This review outlines recent advances in exRNA-based diagnostics for MASLD and MASH, emphasizing their role in early detection, disease monitoring, and the shift toward personalized hepatology.