Baseline serum exosome-derived miRNAs predict HBeAg seroconversion in chronic hepatitis B patients treated with peginterferon.

OBJECTIVE This study aimed to explore the value of baseline serum exosome-derived miRNAs for predicting HBeAg seroconversion in chronic hepatitis B (CHB) patients treated with peginterferon (Peg-IFN). METHODS A total of 120 treatment-naive HBeAg-positive CHB patients who received Peg-IFN therapy (48 weeks) were enrolled. Next-generation sequencing was performed to screen the serum exosomal miRNAs that were associated with Peg-IFN treatment outcome, and qRT-PCR was used to validate them. The area under receiver operating characteristic curve (AUROC) was used to evaluate the predictive efficacy of biomarkers. RESULTS Thirty-three patients (27.5%) achieved HBeAg seroconversion (response group), and 87 patients (72.5%) did not achieve HBeAg seroconversion (non-response group). In the identification cohort, forty serum exosome-derived miRNAs were differentially expressed between the response group (4 patients) and the non-response group (4 patients). In the confirmation cohort, the expression levels of serum exosomal miR-194-5p (p < 0.001) and miR-22-3p (p < 0.001) were significantly downregulated in the response group (29 patients) compared to the non-response group (83 patients). Multivariate analysis identified baseline serum exosomal miR-194-5p, miR-22-3p, alanine aminotransferase (ALT) and HBV DNA as independent predictors of HBeAg seroconversion (all p < 0.05). The AUROCs of serum exosomal miRNAs (0.77 and 0.75 for miR-194-5p and miR-22-3p, respectively) were higher than that of ALT (0.70) and HBV DNA (0.69). The combination of exosomal miR-194-5p and miR-22-3p further improved the predictive performance with an AUROC of 0.82. CONCLUSION Baseline serum exosomal miR-194-5p and miR-22-3p may serve as novel biomarkers to predict HBeAg seroconversion in CHB patients treated with Peg-IFN. This article is protected by copyright. All rights reserved.