P- 77 EPIGENOME OF PATIENTS WITH LIVER FIBROSIS, WITH SUSTAINED VIRAL RESPONSE TO HCV IN LIVER BIOPSY AND LIQUID BIOPSY REVEALS THE ASSOCIATION OF DNA METHYLATION AND miRNA EXPRESSION WITH THE DEGREE OF SEVERITY

Abstract

Introduction and Objectives: It has been shown that DNA methylation patterns and miRNA levels are effective markers for distinguishing different stages of liver fibrosis in European patients. A liquid biopsy allows the evaluation of ccfDNA methylation levels from hepatocytes damaged by necrosis/apoptosis, releasing degraded genomic DNA into the circulatory system, which reflects the gene changes present in hepatocytes. This study aimed to evaluate the potential association of specific miRNAs and the percentage of DNA methylation of genes linked with fibrosis in liver tissue and liquid biopsy from MEXICAN patients with various degrees of liver fibrosis and its severity. Materials and Methods: Transjugular liver biopsies and liquid biopsies were collected from 23 patients with sustained viral response to HCV and residual fibrosis. The percentage of methylation in CpG islands of PPARα, gamma and δ gene promoters, as well as TGFβ1 and PDGFα, will be determined by pyrosequencing in DNA extracted from the liver and ccfDNA. Fibrosis was stratified according to Metavir. miR-21, miR-34, miR-122, miR181b, miR192, and miR-200a/b expression was evaluated. Results: Higher methylation percentages were detected in antifibrotic gene promoters (PPARα and gamma) in patients with more severe degrees of fibrosis (F4), both in tissue and in liquid biopsy. TGFβ1 and PDGFα, profibrogenic genes, showed significant hypomethylation in their promoter regions, indicating hyperactivation. In addition, the overexpression of miRNAs evaluated was associated with the degree of fibrosis and severity. Conclusions: Epigenetic mechanisms (DNA methylation and microRNA expression) regulate the expression of multiple genes and their measurement can be a biomarker associated with the degree of fibrosis. Liquid biopsy is an effective and accessible method for evaluating the degree of fibrosis in Mexican subjects and for monitoring clinical protocols.