HCV patients with residual fibrosis after DAA treatment re-establish their epigenetic signature after prolonged-release pirfenidone: MINERVA study

作者：Eira Cerda‐Reyes, Ricardo de la Rosa-Bibiano, Ana Sandoval-Rodríguez, Rebeca Rosas-Campos, Aldo Torre, Stefanny Cornejo-Hernández, Rebeca Escutia-Gutiérrez, Ángel Vázquez-Esqueda, Jorge Gutiérrez‐Cuevas, Alejandro Gutiérrez-Átemis, Salvador Amézquita-Pérez, Jorge Luis Poo, Gildardo Agustín Garrido-Sánchez, Javier Bastida-Alquicira, Elsa Saldaña-Rivera, Lucila Maritza Lozano-Trenado, Juan Ramón-Aguilar, Jose Alejandro Madrigal, Juan Armendáriz‐Borunda · 发表于：Clinical Epigenetics · 年份：2025 · DOI：10.1186/s13148-025-01969-y · 被引用次数：3 · 研究领域：Hepatitis C virus research、Liver physiology and pathology、Liver Disease Diagnosis and Treatment

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 DN...