Abstract

Measurement of O-glycosylated middle hepatitis B surface antigen (HBsAg glycan isomer, HBsAgGi) has been developed to quantify hepatitis B virus (HBV) infectious virions and distinguish them from subviral particles. This study aimed to evaluate the association between serum HBsAg seroclearance and serum HBV virions measured by HBsAgGi in patients with chronic hepatitis B (CHB). Serum HBsAgGi levels were quantified in 232 treatment-naïve patients with CHB genotype C. Cox proportional hazards analysis was used to calculate hazard ratios (HRs) for factors associated with HBsAg seroclearance. Baseline HBsAgGi levels showed significant differences among HBV phenotypes. During a median follow-up period of 7.4years, 22 of the 232 patients achieved HBsAg seroclearance. Multivariate analysis demonstrated that quantitative HBsAg, nucleoside/nucleotide analog therapy during the follow-up period, and HBsAgGi levels were independent predictors of seroclearance. The adjusted HR indicated that the HBsAg seroclearance probability in patients with low HBsAgGi (≤3.5logng/mL) was over five times higher than that in patients with high HBsAgGi. Kaplan-Meier analysis indicated that the 10-year probabilities of HBsAg seroclearance were 21.0% and 3.0% in patients with low and high HBsAgGi levels, respectively (p<0.001), and that patients with high HBsAgGi levels showed low seroclearance probabilities irrespective of the other predictors. Serum HBV infectious virion levels, measured using HBsAgGi, may be a novel predictor of HBsAg seroclearance.

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