Circulating HBV RNA and HBsAg seroconversion in patients with chronic HBV infection: a long-term follow-up study starting from childhood in Taiwan

Background HBV surface antigen (HBsAg) seroconversion indicates the clearance of HBV in patients with chronic HBV infection. Objective We aimed to investigate the predictive value of HBV RNA and HBV mutants on HBsAg seroconversion in patients with chronic HBV infection from childhood to adulthood. Design We recruited 700 children (409 males and 291 females) with initially hepatitis B e antigen (HBeAg)-positive chronic HBV infection. With the mean initial visit age of 7.28 years (95% CI 7.03 to 7.62 years), they were followed for 15 912 person-years at our institution. Serum samples collected after HBeAg seroconversion in HBeAg seroconverters were analysed for circulating HBV RNA, HBsAg, HBV core-related antigen, HBV DNA levels and the percentage of HBV mutants. Results 23 subjects (3.29%) experienced HBsAg seroconversion following antiviral therapy, while another 27 (3.86%) achieved spontaneous HBsAg seroconversion in this cohort. The annual probability of HBsAg seroconversion is 0.32% (95% CI 0.30% to 0.33%) per person-year across the entire cohort. After HBeAg seroconversion, the spontaneous annual HBsAg seroconversion rate is 0.47% (95% CI 0.42% to 0.51%) per person-year, and it rises to 1.30% (95% CI 1.10% to 1.51%) per person-year in subjects who had previously received antiviral agents before HBeAg seroconversion. Undetectable circulating HBV RNA and the percentage of A2131C mutants <10% after HBeAg seroconversion are significant predictors of HBsAg seroconversion in both univariate and multivariate survival analyses. Conclusion In this long-term chronic HBV cohort, we elucidated both the natural course and antiviral-related HBsAg seroconversion. Undetectable circulating HBV RNA and percentage of A2131C mutants <10% after HBeAg seroconversion are novel and independent predictors of HBsAg seroconversion.