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This is particularly relevant for people with HIV (PWH) with HCV coinfection, a population prone to accelerated liver disease progression. This study aimed to characterize the plasma miRNA profile in PWH with cirrhosis one year after successful completion of HCV therapy, and to explore their relationship with metabolite alterations. Methods: This cross-sectional study enrolled 47 PWH who achieved HCV clearance with antiviral therapy. Using plasma samples collected approximately one year after completion of HCV therapy, participants were stratified into two groups based on liver stiffness measurement (LSM): compensated cirrhosis (n = 32, LSM \u2265 12.5 kPa) and non-cirrhosis (n = 15, LSM &lt; 12.5 kPa). Plasma miRNAs and metabolites were determined using small RNA sequencing and untargeted capillary electrophoresis-mass spectrometry (CE-MS), respectively. Significantly differentially expressed (SDE) miRNAs were identified using generalized linear models (GLM) with a negative binomial distribution, and their correlation with metabolite levels was quantified using Spearman\u2019s correlation. Results: In the cirrhosis group (n = 32), we identified a distinct signature of 15 SDE miRNAs (9 upregulated, 6 downregulated) compared to the non-cirrhotic group (n = 15), showing hsa-miR-10401-3p, hsa-miR-548ak, hsa-miR-141-3p, and hsa-miR-3940-3p the largest expression changes. miRNA-gene interaction and pathway enrichment analysis suggested that these 15 SDE miRNAs potentially regulate multiple genes involved in immune response and amino acid metabolism. In addition, correlation analyses with our metabolomic data revealed significant associations between specific SDE miRNAs and amino acids and their derivatives. Specifically, the expression of upregulated miRNAs (e.g., hsa-miR-10401-3p and hsa-miR-16-5p) was positively correlated with plasma levels of L-methionine and its derivatives, while downregulated miRNAs (e.g., hsa-miR-625-5p) were inversely correlated with L-tryptophan. Conclusions: In cirrhotic PWH with history of HCV coinfection, a distinct plasma miRNA signature linked to dysregulated amino acid metabolism is found one year after completion of HCV therapy. This underscores that the HCV cure does not equate to complete hepatic recovery, highlighting the critical need for long-term monitoring in this high-risk population.<\/jats:p>","DOI":"10.3390\/ph19010170","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:57:02Z","timestamp":1768816622000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plasma miRNA-Metabolite Dysregulation in People with HIV with Cirrhosis Despite Successful HCV Cure"],"prefix":"10.3390","volume":"19","author":[{"given":"Ana","family":"Virseda-Berdices","sequence":"first","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda (CNM), Instituto de Salud Carlos III (ISCIII), 28222 Majadahonda, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"},{"name":"Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Behar-Lagares","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda (CNM), Instituto de Salud Carlos III (ISCIII), 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Berenguer","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"},{"name":"Unidad de Enfermedades Infecciosas\/VIH, Hospital General Universitario \u201cGregorio Mara\u00f1\u00f3n\u201d, 28007 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM), 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3652-002X","authenticated-orcid":false,"given":"Juan","family":"Gonz\u00e1lez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"},{"name":"Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Paz (IdiPAZ), 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4710-0685","authenticated-orcid":false,"given":"Belen","family":"Requena","sequence":"additional","affiliation":[{"name":"Centro de Metabol\u00f3mica y Bioan\u00e1lisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, 28668 Boadilla del Monte, 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Spain"},{"name":"Unidad de Patog\u00e9nesis e Inmunidad Viral, Centro Nacional de Microbiolog\u00eda (CNM), Instituto de Salud Carlos III (ISCIII), 28220 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7026-8684","authenticated-orcid":false,"given":"Carolina","family":"Gonz\u00e1lez-Riano","sequence":"additional","affiliation":[{"name":"Centro de Metabol\u00f3mica y Bioan\u00e1lisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, 28668 Boadilla del Monte, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-491X","authenticated-orcid":false,"given":"Coral","family":"Barbas","sequence":"additional","affiliation":[{"name":"Centro de Metabol\u00f3mica y Bioan\u00e1lisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, 28668 Boadilla del Monte, 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