Baseline serum EV-miR-1-3p as a protective factor and biomarker for hepatocellular carcinoma development after HCV eradication

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BACKGROUND: Direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC) achieves high sustained virologic response (SVR) rates; however, hepatocellular carcinoma (HCC) can still develop after viral eradication. Reliable biomarkers for predicting the post-SVR HCC risk are lacking. This study aimed to identify baseline serum extracellular vesicle microRNAs (EV-miRNAs) associated with HCC development following SVR. MATERIALS AND METHODS: Eleven CHC patients who achieved SVR were retrospectively enrolled as a discovery cohort to identify candidate EV-miRNAs at SVR12 predictive of future HCC. An independent validation cohort of 89 CHC patients was also analyzed. HCC development was defined as the occurrence of HCC at ≥ 12 months after SVR. EV-miRNA profiles were assessed by small RNA sequencing and validated using a miRNA enzyme immunoassay (miREIA). RESULTS: In the discovery cohort, four EV-miRNAs (EV-miR-1-3p, EV-miR-148a-3p, EV-miR-223-3p, and EV-miR-4433b-5p) were significantly different between patients who later developed HCC and those who remained HCC-free at SVR12. In the 89-patient validation cohort, 51 (57.3%) developed HCC with a median disease-free survival (DFS) of 23.1 months, and 12 (13.5%) patients died during a median follow-up of 77 months. High baseline EV-miR-1-3p and EV-miR-148a-3p levels and low EV-miR-4433b-5p were associated with remaining HCC-free. Elevated EV-miR-1-3p and EV-miR-148a-3p levels were also correlated with longer DFS (p < 0.05). In multivariate analysis, EV-miR-1-3p was the only independent predictor of longer DFS (adjusted hazard ratio [HR] 0.459, p = 0.014) and improved overall survival (OS) (adjusted HR 0.390, p = 0.016) after SVR12. Among all biomarkers evaluated, baseline EV-miR-1-3p demonstrated the highest predictive accuracy for HCC occurrence (area under the curve [AUC] 0.843, vs. 0.769 for alpha-fetoprotein [AFP] and 0.755 for FIB-4; p < 0.001) and for OS (AUC 0.876, vs. 0.480 for AFP and 0.655 for FIB-4; p < 0.001). Furthermore, patients with high EV-miR-1-3p levels showed higher platelet counts and albumin, and a lower proportion with FIB-4 ≥ 3.25, suggesting that high EV-miR-1-3p reflects better preserved liver function and less advanced fibrosis. CONCLUSIONS: Baseline serum EV-miR-1-3p serves as a protective biomarker for stratifying HCC risk and predicting survival in CHC patients after HCV eradication via DAA therapy.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.