Extracellular vesicle-derived candidate biomarker in metabolic dysfunction-associated steatotic liver disease: systematic review and exploratory meta-analysis

Abstract

Abstract Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is raising global concern, highlighting the need for simple, reliable, and non-invasive diagnostic tools. Extracellular vesicles (EVs) are well-known nano-carriers of circulating biomarkers, which are often involved in disease development and intercellular communication. The current review aims to synthesise and analyse the evidence from the exploratory diagnostic studies examining the EV-derived biomarkers in MASLD. A detailed literature search across three electronic databases, including PubMed, Scopus, and Embase, resulted in 3440 records, of which 7 eligible studies were selected for further data synthesis. Quality assessment for the included studies was carried out adhering to Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines. The meta-analysis was performed using unique analytic strategies, including area under the curve (AUC)-based analyses for EV-derived panels and biomarkers in MASLD. The meta-analysis results indicated that the diagnostic accuracy associated with the plasma-derived EV microRNAs (miRNAs) was considerable for the exploratory studies and needs further validation for clinical practice. Overall, systematically synthesised evidence suggests that the EV-derived miRNAs might serve as clinically useful diagnostic biomarkers for early-stage MASLD. However, the exploratory nature of the literature, which involved high heterogeneity across the study design, sample processing, and analysis, caused difficulty in generalising the conclusions, thus suggesting the need for standardisation. Overall, the present review provides a detailed synthesis of exploratory research, emphasising the diagnostic value of EV-derived biomarkers.