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

Abstract

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‐naïve 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.