2026-08-25T12:44:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/276592026-08-19T08:40:53Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Cairoli, Victoria
author
Valle-Millares, Daniel
author
Ryan, Pablo
author
Dominguez, Lourdes
author
Martín-Carbonero, Luz
author
De Los Santos, Ignacio
author
De Matteo, Elena
author
Ameigeiras, Beatriz
author
De Sousa, Marcela
author
Briz, Veronica
author
Preciado, María V
author
Fernandez-Rodriguez, Amanda
author
Valva, Pamela
funder
Instituto de Salud Carlos III
funder
RETICS-Sida (RIS-ISCIII) (España)
funder
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
funder
Agencia Nacional de Promoción Científica y Tecnológica (Argentina)
funder
National Scientific and Technical Research Council (Argentina)
2026-08-17T12:08:35Z
2026-08-17T12:08:35Z
2025-06
Cairoli V, Valle-Millares D, Ryan P, Dominguez L, Martín-Carbonero L, De Los Santos I, De Matteo E, Ameigeiras B, De Sousa M, Briz V, Preciado MV, Fernández-Rodriguez A, Valva P. Extracellular vesicles derived microRNAs as non-invasive markers of liver fibrosis in chronically infected HCV patients: a pilot study. Noncoding RNA Res. 2025 Mar 5;12:132-140. doi: 10.1016/j.ncrna.2025.03.004. PMID: 40176849; PMCID: PMC11964596.
10.1016/j.ncrna.2025.03.004
Non-coding RNA Research
40176849
https://hdl.handle.net/20.500.12105/27659
Extracellular vesicles (EVs) are an increasingly promising tool for liquid biopsy in liver diseases. Hepatitis C Virus (HCV) infection, alone or together with Human Immunodeficiency Virus (HIV) infection significantly impacts on the microRNA (miRNA) EVs content resembling chronic hepatitis C (CHC) progression. The objective of the study was to delve into the intricate EVs-miRNA profiles in CHC patients with different liver fibrosis stages, aiming to pinpoint non-invasive markers capable of distinguishing significant fibrosis. Plasma EV-miRNAs from 50 CHC patients (HCV+ and HCV+/HIV+) stratified in no significant (F < 2) and significant (F ≥ 2) fibrosis, were massively sequenced. General linear models (GLM) were used to identify significantly differential expressed (SDE) miRNAs according to liver fibrosis stages (F ≥ 2 and F < 2). Dysregulated biological pathways were subsequently analyzed for the following groups: i) all patients; ii) HCV+; and iii) HCV+/HIV+. Multiple-ordered logistic regression analysis was performed to develop a score to identify F ≥ 2 cases. The diagnostic potential of both the SDE miRNAs and the developed score was assessed using ROC curve analysis. With respect to all CHC patients, two SDE miRNAs (hsa-miR-122-5p and hsa-miR-92a-3p) were identified which regulate genes related to cytoskeleton organization. Regarding their diagnostic performance to discriminate F ≥ 2, both miRNAs individually demonstrated acceptable diagnostic values. However, their combined use in a new score enhanced their diagnostic performance (AUROC = 0.833). In the HCV+ subgroup, 8 SDE miRNAs (hsa-miR-122-5p, hsa-miR-320c, hsa-miR-3615, hsa-miR-320a-3p, hsa-miR-374b-5p, hsa-let-7a-3p, hsa-miR-199a-5p, hsa-miR-142-5p), which regulate macrophage activity and cell growth/death regulation, were recognized. Among them, hsa-miR-3615 displayed the highest diagnostic performance to discriminate F ≥ 2 (AUROC = 0.936). With respect to HCV+/HIV+, 18 SDE miRNAs (hsa-miR-4508, hsa-miR-122-5p, hsa-miR-451a, hsa-miR-1290, hsa-miR-1246, hsa-miR-107, hsa-miR-15b-5p, hsa-miR-194-5p, hsa-miR-22-5p, hsa-miR-20b-5p, hsa-miR-142-5p, hsa-miR-328-3p, hsa-miR-335-3p, hsa-miR-125a-5p, hsa-miR-423-3p, hsa-let-7d-3p, hsa-miR-128-3p, hsa-miR-10a-5p) were recognized that regulate RNA silencing processes. In this case, hsa-miR-423-3p and hsa-miR-128-3p showed outstanding diagnostic performances (AUROC > 0.900). Distinct EVs-miRNA profiles were identified in patients with varying liver fibrosis stages, both in the overall CHC cohort and within HCV+ and HCV+/HIV+ subgroups. These specific miRNA signatures would allow the elucidation of potential mechanisms involved in clinical evolution and identification of specific biomarkers of unfavorable progression, plausible to be used in a diagnostic panel. Furthermore, the developed score demonstrates the ability to discriminate within the CHC group those individuals with significant fibrosis regardless of their HIV infection status.
eng
Biomarkers
Extracellular vesicles
Fibrosis
Hepatitis C infections
MicroRNAs
Extracellular vesicles derived microRNAs as non-invasive markers of liver fibrosis in chronically infected HCV patients: a pilot study.
research article
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