P-41 MICRORNAs FROM EVs AS POTENTIAL LIVER FIBROSIS NON-INVASIVE BIOMARKERS IN CHRONIC HEPATITIS C

Conflict of interest

No

Introduction and Objectives

Liver fibrosis evaluation is essential in management of chronic hepatitis C (CHC). Extracellular vesicles (EVs) are essential components of liquid biopsy. MicroRNAs (miRNAs) within EVs could serve as biomarkers of damage due to their role in regulating fibrogenesis through gene expression modulation. The objective was: evaluate plasma derived (p)EVs-miRNAs as biomarkers of significant fibrosis (F≥2) in CHC.

Patients / Materials and Methods

pEVs were isolated using exoRNeasy kit (QIAGEN) from 50 CHC cases (36% F≥2, assessed by liver fibrosis). miRNA-enriched RNA was extracted, sequenced by NGS and significant differential expression (SDE) analysis was performed between F≥2 and F<2 cases [fold change (FC)≥1.5; false discovery rate (FDR)≤0.2]. Diagnostic value of SDE miRNAs was assessed using ROC curves analysis. A score to predict significant fibrosis was generated by a binomial logistic regression model and its performance was compared with those of APRI and FIB-4 indexes. Plasma expression of SDE miRNAs was evaluated by RT-qPCR.

Results and Discussion

SDE analysis showed upregulation of miR-122-5p (FC=3.06, FDR<0.001) and downregulation of miR-92a-3p (FC=-1.5, FDR=0.051) in pEVs from F≥2 individuals. Each miRNA showed moderate power to discriminate F≥2 cases, but excellent power in the generated score (AUROC_miR-122=0.746; AUROC_miR-92a=0.767; AUROC_score=0.858). By APRI and FIB-4 indexes, 15 and 14 cases were classified as indeterminate, respectively. The score managed to correctly classify 11 APRI and 13 FIB-4 misclassified cases (Table 1). In plasma, no differences were observed in miRNA expression between fibrosis stages (p-value_miR-122=0.874; p-value_miR-92a=0.650).

Conclusions

Different stages of liver fibrosis showed specific pEVs-miRNA expression signatures. The combined evaluation of miR-122 and miR-92a in the score demonstrated excellent performance for discriminating F≥2 cases and improve APRI and FIB-4 performances. Direct plasma evaluation did not reflect the profiles observed in pEVs, highlighting the value of pEVs as potential biomarkers of liver fibrosis.