ArticleJournal of clinical and translational hepatology2025
Plasma Extracellular Vesicle-derived MicroRNA Associated with Human Alpha-1 Antitrypsin Deficiency-mediated Liver Disease.
Article in Journal of clinical and translational hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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10 authors.
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Abstract
Background and Aims: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals. Methods: Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45). Results: We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composite scores with three- and four-miRNA combinations, achieving areas under the curve of 0.737 and 0.751, respectively, for predicting AATD liver disease. Conclusions: We introduce plasma EV-derived miRNAs as potential biomarkers for evaluating AATD liver disease. Plasma EV-associated miRNAs may represent a molecular signature of AATD liver disease and could serve as valuable tools for its detection and monitoring.
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