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. 2025 Aug;81(3):589-609.
doi: 10.1007/s13105-025-01110-w. Epub 2025 Jul 16.

The use of circulating miRNAs for the diagnosis, prognosis, and personalized treatment of MASLD

Ana Luz Tobaruela-Resola  1 , Fermín I Milagro  2   3   4 , Paola Mogna-Pelaez  1 , María Jesús Moreno-Aliaga  1   5   6 , Itziar Abete #  1   5   6 , María Ángeles Zulet #  1   5   6
Affiliations

The use of circulating miRNAs for the diagnosis, prognosis, and personalized treatment of MASLD

Ana Luz Tobaruela-Resola et al. J Physiol Biochem. 2025 Aug.

Abstract

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly NAFLD, includes a range of conditions from steatosis to hepatocellular carcinoma and poses a significant health and economic burden. Circulating microRNAs (miRNAs) are key regulators of metabolic and inflammatory pathways involved in MASLD. However, their clinical utility as non-invasive biomarkers remain unclear. This review aims to clarify their diagnostic, prognostic, and therapeutic potential, addressing current gaps in the literature.

Methods: Following PRISMA guidelines, we conducted a systematic review of 1149 studies from the PubMed and Scopus databases up to 2024, focused on circulating miRNAs in MASLD.

Results: The most frequently studied miRNAs included miR-122 (35.56% of studies), miR-21 (18.89%), miR-34 (14.44%), and miR-192-5p (13.33%). Diagnostic accuracy varied among miRNAs, with miR-200 and miR-298 demonstrating AUROCs of 0.96 and 0.98, respectively, for MASLD detection. In MASH, miR-200, miR-298, and miR-342 exhibited near-perfect AUROCs of 0.99, while miR-122 showed values between 0.81 and 1.0. For HCC, miR-214 achieved an AUROC of 0.88, and miR-34a ranged from 0.73 to 0.76. Several miRNA panels demonstrated high diagnostic accuracy, with AUROCs up to 0.99, particularly in distinguishing HCC from other liver conditions. Prognostically, elevated miR-122 levels correlated with disease severity and fibrosis progression, while miR-21 and miR-223 were linked to obesity-associated MASH. Therapeutic interventions, including surgery, dietary modifications, and supplementation, were found to modulate miRNA profiles.

Conclusions: MiRNAs exhibit strong potential as minimally invasive biomarkers for MASLD, contributing to improved diagnosis, prognosis, and therapeutic decision-making. Their stability and role in personalized medicine underscore their clinical relevance.

Keywords: Circulating MiRNAs; Diagnosis; MASLD; Minimally invasive biomarkers; Personalized treatment; Prognosis.

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Conflict of interest statement

Declarations. Ethics approval: This work is not research involving humans or animals. Human ethics and consent to participate declarations: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare no relevant or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Flowchart of the systematic review Abbreviations: MASLD, Metabolic Dysfunction-Associated Steatotic Liver Disease; MASH, Metabolic Dysfunction-Associated Steatohepatitis; miRNA, microRNA
Fig. 2
Fig. 2
MiRNAs mentioned in all studies of this review. Abbreviations: miRNA, microRNA
Fig. 3
Fig. 3
Distribution of sample sources and their frequency in the systematic review. Abbreviations: FFPE, Formalin-Fixed Paraffin-Embedded
Fig. 4
Fig. 4
Geographical distribution of the institutions involved in the studies about miRNAs
See this image and copyright information in PMC

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