1. P-26 EPIGENETIC MARKS IN PATIENTS WITH SUSTAINED VIRAL RESPONSE TO HCV AND RESIDUAL LIVER FIBROSIS ARE RESTORED BY PROLONGED-RELEASE PIRFENIDONE
- Author
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Eira Cerda Reyes, Ricardo De la Rosa Bibiano, Ana Sandoval Rodriguez, Rebeca Rosas Campos, Rebeca Escutia Gutiérrez, Ángel Omar Vázquez Esqueda, Stefanny Cornejo Hernández, Alejandro Gutiérrez Átemis, Salvador Amezquita Pérez, Jorge Luis Poo, Gildardo Agustin Garrio Sanchez, Juan Ramón Aguilar, and Juan Armendáriz Borunda
- Subjects
Specialties of internal medicine ,RC581-951 - Abstract
Conflict of interest: No Introduction and Objectives: Patients with residual liver fibrosis following the eradication of hepatitis C virus (HCV) represent a significant clinical challenge due to the continuous risk of disease progression and the development of hepatocellular carcinoma. This study aimed to evaluate the efficacy of a 12-month treatment with prolonged-release pirfenidone (PR-PFD) plus standard of care for the regression of liver fibrosis and its effect on key epigenetic marks. Patients / Materials and Methods: HCV patients who responded to direct-acting antivirals (DAAs) and had residual fibrosis received PR-PFD (1200 mg/day) for 12 months. Liver biopsies and serum samples were analyzed at the beginning and end of the treatment. Additionally, six non-fibrotic controls were included to compare the epigenetic marks. Results and Discussion: 38 patients completed the 12-month treatment, and 28.94% showed a reduction of at least one fibrosis stage according to liver biopsies, while 57.57% experienced an improvement in fibrosis according to transient elastography. Levels of bilirubin, alkaline phosphatase, AST, INR, and APRI significantly decreased. Profibrogenic miRNAs (miR-34a, miR-21, miR-16, miR-181b, miR-200a, and miR-200b) showed a significant increase in advanced fibrosis compared to non-fibrotic controls. Notably, PR-PFD treatment restored the expression of miR-34a, miR-16, miR-192, miR-200a, and miR-122. In cell-free DNA (liquid biopsy), PDGFα showed hypermethylation in patients with mild fibrosis, while in liver tissue hypomethylation was present in non-fibrotic controls. In the circulating DNA of non-fibrotic controls, PPAR-δ was hypermethylated compared to mild and advanced fibrosis cohorts. Treatment with PR-PFD induced hypermethylation in three islets of TGFβ1, suggesting a decrease in the transcription of this profibrogenic cytokine. Conclusions: These findings indicate, for the first time, that PR-PFD treatment could exert therapeutic effects in Hispanic patients with residual fibrosis by modulating miRNA expression and methylation of specific CpG sites.
- Published
- 2024
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