PBMCs gene expression predicts liver fibrosis regression after successful HCV therapy in HIV/HCV-coinfected patients
BackgroundHCV eradication with antiviral treatment reduces hepatic disease, but some patients remain at risk of progression to cirrhosis despite HCV clearance. We aimed to examine the association between peripheral blood mononuclear cells (PBMCs) gene expression before HCV therapy and a pronounced d...
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Frontiers Media S.A.
2025-01-01
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| author | Ana Virseda-Berdices Ana Virseda-Berdices Óscar Brochado-Kith Óscar Brochado-Kith Juan Berenguer Juan Berenguer Juan Berenguer Juan González-García Juan González-García Juan González-García Leire Pérez-Latorre Leire Pérez-Latorre Leire Pérez-Latorre Carmen Busca Carmen Busca Carmen Busca Cristina Díez Cristina Díez Cristina Díez Rafael Micán Rafael Micán Rafael Micán Amanda Fernández-Rodríguez Amanda Fernández-Rodríguez María Ángeles Jiménez-Sousa María Ángeles Jiménez-Sousa Salvador Resino Salvador Resino |
| author_facet | Ana Virseda-Berdices Ana Virseda-Berdices Óscar Brochado-Kith Óscar Brochado-Kith Juan Berenguer Juan Berenguer Juan Berenguer Juan González-García Juan González-García Juan González-García Leire Pérez-Latorre Leire Pérez-Latorre Leire Pérez-Latorre Carmen Busca Carmen Busca Carmen Busca Cristina Díez Cristina Díez Cristina Díez Rafael Micán Rafael Micán Rafael Micán Amanda Fernández-Rodríguez Amanda Fernández-Rodríguez María Ángeles Jiménez-Sousa María Ángeles Jiménez-Sousa Salvador Resino Salvador Resino |
| author_sort | Ana Virseda-Berdices |
| collection | DOAJ |
| description | BackgroundHCV eradication with antiviral treatment reduces hepatic disease, but some patients remain at risk of progression to cirrhosis despite HCV clearance. We aimed to examine the association between peripheral blood mononuclear cells (PBMCs) gene expression before HCV therapy and a pronounced decrease in the liver stiffness measurement (LSM) value in HIV/HCV-coinfected patients after HCV treatment and achievement of sustained virological response (SVR).MethodsWe performed a retrospective study in 48 HIV/HCV-coinfected patients who started anti-HCV treatment with at least advanced fibrosis (LSM ≥9.5). Total RNA was extracted from PBMCs at baseline, and poly(A) RNA sequencing was performed. The outcome was an LSM reduction greater than 50% (LSMred>50%) about 48 weeks after HCV treatment.ResultsSeven patients (14.5%) reduced LSM by over 50%. We found 47 significant differentially expressed (SDE) genes associated with reaching an LSMred>50% after achieving HCV eradication, 42 upregulated and 5 downregulated in the LSMred>50% group. Ten and five of these upregulated genes were classified into two significantly enriched KEGG pathways: cell cycle and progesterone-mediated oocyte maturation (q-value <0.05), respectively. Two SDE genes achieved excellent discrimination ability: NCAPG had an AUROC of 0.908, NHLRC1 of 0.879, and a logistic regression model with these two genes of 0.955.ConclusionA pre-treatment gene expression signature in PBMCs was associated with liver fibrosis regression (LSMred>50%) after achieving HCV clearing with HCV therapy in HIV/HCV-coinfected patients, where two SDE genes (NCAPG and NHLRC1) showed the greatest predictive capacity, which could be used as a noninvasive marker of liver fibrosis regression. |
| format | Article |
| id | doaj-art-79ae9ec7bd7247bbaafbbb46a25e2cae |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-79ae9ec7bd7247bbaafbbb46a25e2cae2025-01-22T07:16:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.14361981436198PBMCs gene expression predicts liver fibrosis regression after successful HCV therapy in HIV/HCV-coinfected patientsAna Virseda-Berdices0Ana Virseda-Berdices1Óscar Brochado-Kith2Óscar Brochado-Kith3Juan Berenguer4Juan Berenguer5Juan Berenguer6Juan González-García7Juan González-García8Juan González-García9Leire Pérez-Latorre10Leire Pérez-Latorre11Leire Pérez-Latorre12Carmen Busca13Carmen Busca14Carmen Busca15Cristina Díez16Cristina Díez17Cristina Díez18Rafael Micán19Rafael Micán20Rafael Micán21Amanda Fernández-Rodríguez22Amanda Fernández-Rodríguez23María Ángeles Jiménez-Sousa24María Ángeles Jiménez-Sousa25Salvador Resino26Salvador Resino27Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainUnidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Maranón”, Madrid, SpainInstituto de Investigación Sanitaria del Gregorio Maranón, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainUnidad de VIH; Servicio de Medicina Interna, Hospital Universitario “La Paz”, Madrid, SpainInstituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainUnidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Maranón”, Madrid, SpainInstituto de Investigación Sanitaria del Gregorio Maranón, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainUnidad de VIH; Servicio de Medicina Interna, Hospital Universitario “La Paz”, Madrid, SpainInstituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainUnidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Maranón”, Madrid, SpainInstituto de Investigación Sanitaria del Gregorio Maranón, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainUnidad de VIH; Servicio de Medicina Interna, Hospital Universitario “La Paz”, Madrid, SpainInstituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, SpainUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, SpainBackgroundHCV eradication with antiviral treatment reduces hepatic disease, but some patients remain at risk of progression to cirrhosis despite HCV clearance. We aimed to examine the association between peripheral blood mononuclear cells (PBMCs) gene expression before HCV therapy and a pronounced decrease in the liver stiffness measurement (LSM) value in HIV/HCV-coinfected patients after HCV treatment and achievement of sustained virological response (SVR).MethodsWe performed a retrospective study in 48 HIV/HCV-coinfected patients who started anti-HCV treatment with at least advanced fibrosis (LSM ≥9.5). Total RNA was extracted from PBMCs at baseline, and poly(A) RNA sequencing was performed. The outcome was an LSM reduction greater than 50% (LSMred>50%) about 48 weeks after HCV treatment.ResultsSeven patients (14.5%) reduced LSM by over 50%. We found 47 significant differentially expressed (SDE) genes associated with reaching an LSMred>50% after achieving HCV eradication, 42 upregulated and 5 downregulated in the LSMred>50% group. Ten and five of these upregulated genes were classified into two significantly enriched KEGG pathways: cell cycle and progesterone-mediated oocyte maturation (q-value <0.05), respectively. Two SDE genes achieved excellent discrimination ability: NCAPG had an AUROC of 0.908, NHLRC1 of 0.879, and a logistic regression model with these two genes of 0.955.ConclusionA pre-treatment gene expression signature in PBMCs was associated with liver fibrosis regression (LSMred>50%) after achieving HCV clearing with HCV therapy in HIV/HCV-coinfected patients, where two SDE genes (NCAPG and NHLRC1) showed the greatest predictive capacity, which could be used as a noninvasive marker of liver fibrosis regression.https://www.frontiersin.org/articles/10.3389/fphar.2024.1436198/fullHIV/HCV coinfectiongene expressionRNA-seqPBMCsliver stiffnessHCV treatment |
| spellingShingle | Ana Virseda-Berdices Ana Virseda-Berdices Óscar Brochado-Kith Óscar Brochado-Kith Juan Berenguer Juan Berenguer Juan Berenguer Juan González-García Juan González-García Juan González-García Leire Pérez-Latorre Leire Pérez-Latorre Leire Pérez-Latorre Carmen Busca Carmen Busca Carmen Busca Cristina Díez Cristina Díez Cristina Díez Rafael Micán Rafael Micán Rafael Micán Amanda Fernández-Rodríguez Amanda Fernández-Rodríguez María Ángeles Jiménez-Sousa María Ángeles Jiménez-Sousa Salvador Resino Salvador Resino PBMCs gene expression predicts liver fibrosis regression after successful HCV therapy in HIV/HCV-coinfected patients Frontiers in Pharmacology HIV/HCV coinfection gene expression RNA-seq PBMCs liver stiffness HCV treatment |
| title | PBMCs gene expression predicts liver fibrosis regression after successful HCV therapy in HIV/HCV-coinfected patients |
| title_full | PBMCs gene expression predicts liver fibrosis regression after successful HCV therapy in HIV/HCV-coinfected patients |
| title_fullStr | PBMCs gene expression predicts liver fibrosis regression after successful HCV therapy in HIV/HCV-coinfected patients |
| title_full_unstemmed | PBMCs gene expression predicts liver fibrosis regression after successful HCV therapy in HIV/HCV-coinfected patients |
| title_short | PBMCs gene expression predicts liver fibrosis regression after successful HCV therapy in HIV/HCV-coinfected patients |
| title_sort | pbmcs gene expression predicts liver fibrosis regression after successful hcv therapy in hiv hcv coinfected patients |
| topic | HIV/HCV coinfection gene expression RNA-seq PBMCs liver stiffness HCV treatment |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1436198/full |
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