Eira Cerda-Reyes, Ricardo de la Rosa-Bibiano, Ana Sandoval-Rodriguez, Rebeca Rosas-Campos, Aldo Torre, Stefanny Cornejo-Hernández, Rebeca Escutia-Gutiérrez, Ángel Vázquez-Esqueda, Jorge Gutierrez-Cuevas, Alejandro Gutiérrez-Átemis, Salvador Amezquita-Pérez, Jorge Luis Poo, Gildardo Agustin Garrido-Sánchez, Javier Bastida-Alquicira, Elsa Saldaña-Rivera, Lucila Maritza Lozano-Trenado, Juan Ramón-Aguilar, Jose Alejandro Madrigal, Juan Armendariz-Borunda
{"title":"经DAA治疗后残留纤维化的HCV患者在缓释吡非尼酮后重新建立其表观遗传特征：MINERVA研究","authors":"Eira Cerda-Reyes, Ricardo de la Rosa-Bibiano, Ana Sandoval-Rodriguez, Rebeca Rosas-Campos, Aldo Torre, Stefanny Cornejo-Hernández, Rebeca Escutia-Gutiérrez, Ángel Vázquez-Esqueda, Jorge Gutierrez-Cuevas, Alejandro Gutiérrez-Átemis, Salvador Amezquita-Pérez, Jorge Luis Poo, Gildardo Agustin Garrido-Sánchez, Javier Bastida-Alquicira, Elsa Saldaña-Rivera, Lucila Maritza Lozano-Trenado, Juan Ramón-Aguilar, Jose Alejandro Madrigal, Juan Armendariz-Borunda","doi":"10.1186/s13148-025-01969-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background & aims: </strong>Patients with residual liver fibrosis after hepatitis C virus infection clearance represent an important challenge. The primary objective of this study was to evaluate epigenetic marks in DAA-responders HCV, Hispanic patients with remaining fibrosis who were treated with prolonged-release pirfenidone (PR-PFD).</p><p><strong>Methods: </strong>Forty-four DAA-responders HCV patients presenting remaining fibrosis received PR-PFD (1200 mg/day) for 12 months. Liver biopsies and serum samples were analyzed. Patients were classified as regressive fibrotic profile (RFP), stable fibrosis profile (SFP), or progressive fibrotic profile (PFP) based on liver stiffness (Fibroscan) (± 30% variation). A control cohort of 20 DAA-responders HCV patients received only standard of care treatment. Additionally, six non-fibrotic controls were included to compare epigenetic marks.</p><p><strong>Results: </strong>Thirty-eight patients completed the 12-month treatment; 28.94% showed a reduction in at least one fibrosis stage based on liver biopsies. Fibroscan revealed that 44.73% of patients in the PR-PFD group exhibited RFP. Bilirubin, alkaline phosphatase, AST, INR and APRI values significantly decreased in this group. Noteworthy, 85% of 20 control patients had SFP. Profibrogenic miRNAs displayed a significant increase in expression in advanced fibrosis versus controls without fibrosis. PR-PFD treatment restored the expression of miR-34a, miR-16, miR-192, miR-200a, and miR-122. PDGFA CpGs hypermethylation in both cell-free DNA and liver biopsies has been found in advanced fibrosis. Interestingly, four CpGs in PPARD were hypomethylated compared to controls. PR-PFD treatment resulted in hypermethylation of three TGFB1-CpGs.</p><p><strong>Conclusion: </strong>These findings indicate for the first time that PR-PFD might exert therapeutic effects in Hispanic patients with residual fibrosis by modulating the expression of miRNAs and methylation of specific CpG sites.</p><p><strong>Clinical trial number: </strong>NCT05542615. Registration Date 09/13/2022.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"157"},"PeriodicalIF":4.4000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495695/pdf/","citationCount":"0","resultStr":"{\"title\":\"HCV patients with residual fibrosis after DAA treatment re-establish their epigenetic signature after prolonged-release pirfenidone: MINERVA study.\",\"authors\":\"Eira Cerda-Reyes, Ricardo de la Rosa-Bibiano, Ana Sandoval-Rodriguez, Rebeca Rosas-Campos, Aldo Torre, Stefanny Cornejo-Hernández, Rebeca Escutia-Gutiérrez, Ángel Vázquez-Esqueda, Jorge Gutierrez-Cuevas, Alejandro Gutiérrez-Átemis, Salvador Amezquita-Pérez, Jorge Luis Poo, Gildardo Agustin Garrido-Sánchez, Javier Bastida-Alquicira, Elsa Saldaña-Rivera, Lucila Maritza Lozano-Trenado, Juan Ramón-Aguilar, Jose Alejandro Madrigal, Juan Armendariz-Borunda\",\"doi\":\"10.1186/s13148-025-01969-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background & aims: </strong>Patients with residual liver fibrosis after hepatitis C virus infection clearance represent an important challenge. The primary objective of this study was to evaluate epigenetic marks in DAA-responders HCV, Hispanic patients with remaining fibrosis who were treated with prolonged-release pirfenidone (PR-PFD).</p><p><strong>Methods: </strong>Forty-four DAA-responders HCV patients presenting remaining fibrosis received PR-PFD (1200 mg/day) for 12 months. Liver biopsies and serum samples were analyzed. Patients were classified as regressive fibrotic profile (RFP), stable fibrosis profile (SFP), or progressive fibrotic profile (PFP) based on liver stiffness (Fibroscan) (± 30% variation). A control cohort of 20 DAA-responders HCV patients received only standard of care treatment. Additionally, six non-fibrotic controls were included to compare epigenetic marks.</p><p><strong>Results: </strong>Thirty-eight patients completed the 12-month treatment; 28.94% showed a reduction in at least one fibrosis stage based on liver biopsies. Fibroscan revealed that 44.73% of patients in the PR-PFD group exhibited RFP. Bilirubin, alkaline phosphatase, AST, INR and APRI values significantly decreased in this group. Noteworthy, 85% of 20 control patients had SFP. Profibrogenic miRNAs displayed a significant increase in expression in advanced fibrosis versus controls without fibrosis. PR-PFD treatment restored the expression of miR-34a, miR-16, miR-192, miR-200a, and miR-122. PDGFA CpGs hypermethylation in both cell-free DNA and liver biopsies has been found in advanced fibrosis. Interestingly, four CpGs in PPARD were hypomethylated compared to controls. PR-PFD treatment resulted in hypermethylation of three TGFB1-CpGs.</p><p><strong>Conclusion: </strong>These findings indicate for the first time that PR-PFD might exert therapeutic effects in Hispanic patients with residual fibrosis by modulating the expression of miRNAs and methylation of specific CpG sites.</p><p><strong>Clinical trial number: </strong>NCT05542615. 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HCV patients with residual fibrosis after DAA treatment re-establish their epigenetic signature after prolonged-release pirfenidone: MINERVA study.
Background & aims: Patients with residual liver fibrosis after hepatitis C virus infection clearance represent an important challenge. The primary objective of this study was to evaluate epigenetic marks in DAA-responders HCV, Hispanic patients with remaining fibrosis who were treated with prolonged-release pirfenidone (PR-PFD).
Methods: Forty-four DAA-responders HCV patients presenting remaining fibrosis received PR-PFD (1200 mg/day) for 12 months. Liver biopsies and serum samples were analyzed. Patients were classified as regressive fibrotic profile (RFP), stable fibrosis profile (SFP), or progressive fibrotic profile (PFP) based on liver stiffness (Fibroscan) (± 30% variation). A control cohort of 20 DAA-responders HCV patients received only standard of care treatment. Additionally, six non-fibrotic controls were included to compare epigenetic marks.
Results: Thirty-eight patients completed the 12-month treatment; 28.94% showed a reduction in at least one fibrosis stage based on liver biopsies. Fibroscan revealed that 44.73% of patients in the PR-PFD group exhibited RFP. Bilirubin, alkaline phosphatase, AST, INR and APRI values significantly decreased in this group. Noteworthy, 85% of 20 control patients had SFP. Profibrogenic miRNAs displayed a significant increase in expression in advanced fibrosis versus controls without fibrosis. PR-PFD treatment restored the expression of miR-34a, miR-16, miR-192, miR-200a, and miR-122. PDGFA CpGs hypermethylation in both cell-free DNA and liver biopsies has been found in advanced fibrosis. Interestingly, four CpGs in PPARD were hypomethylated compared to controls. PR-PFD treatment resulted in hypermethylation of three TGFB1-CpGs.
Conclusion: These findings indicate for the first time that PR-PFD might exert therapeutic effects in Hispanic patients with residual fibrosis by modulating the expression of miRNAs and methylation of specific CpG sites.
Clinical trial number: NCT05542615. Registration Date 09/13/2022.
期刊介绍：
Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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