Overview
Chronic hepatitis B virus (HBV) infection is a persistent infection that can lead to liver inflammation and damage. The primary goal of novel antiviral treatments is to achieve a "functional" cure, defined by sustained suppression of HBV DNA and loss of hepatitis B surface antigen (HBsAg) 1.Diagnosis
Management
Novel antiviral treatments have shown limited effectiveness in achieving HBsAg loss and reduction, with minimal functional cure rates observed in a meta-analysis 1.
Bepirovirsen, an antisense oligonucleotide, targets all HBV messenger RNAs to decrease viral protein levels. A phase 2b study evaluated bepirovirsen in patients receiving or not receiving nucleos(t)ide analogue (NA) therapy 34.
In a phase 2b trial, bepirovirsen treatment resulted in a primary outcome event (HBsAg below limit of detection and HBV DNA below limit of quantification maintained for 24 weeks post-treatment) in 9% of participants receiving NA therapy in one arm and 0% in another arm 4.
Antiviral therapy in immune-tolerant HBV-infected patients showed a trend towards HBsAg loss, but the evidence was not statistically significant 2.
Pegylated interferon (Peg-IFN) treatment in inactive HBsAg carriers (IHCs) resulted in a 47% HBsAg clearance rate at 48 weeks, significantly higher than the 1.54% clearance rate in control groups (NA treatment or no treatment) 5.Special Populations
Key Recommendations
Novel antiviral treatments have demonstrated limited efficacy in achieving functional cure and HBsAg loss in chronic hepatitis B patients 1. (Evidence: Strong)
Bepirovirsen, an antisense oligonucleotide, has shown potential for HBsAg reduction in chronic hepatitis B, with ongoing phase 2b studies evaluating its efficacy and safety in various treatment regimens 34. (Evidence: Moderate)
Pegylated interferon may be considered for inactive HBsAg carriers to achieve a clinical cure, demonstrating significantly higher HBsAg clearance rates compared to nucleos(t)ide analogues or no treatment 5. (Evidence: Moderate)References
1 Chen J, Ji D, Jia J, Zhuang H, Zhang X, Wang FS et al.. Functional cure with new antiviral therapy for hepatitis B virus: a systematic review and meta-analysis. Hepatology international 2025. link
2 Huang J, Liu Y, Liu Y. Antiviral therapy in hepatitis B virus-infected with immune-tolerant: A meta-analysis. Gastroenterologia y hepatologia 2023. link
3 Cremer J, Elston R, Campbell FM, Kendrick S, Paff M, Quinn G et al.. B-Clear Phase 2b Study Design: Establishing the Efficacy and Safety of Bepirovirsen in Patients with Chronic Hepatitis B Virus Infection. Advances in therapy 2023. link
4 Yuen MF, Lim SG, Plesniak R, Tsuji K, Janssen HLA, Pojoga C et al.. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. The New England journal of medicine 2022. link
5 Song A, Lin X, Lu J, Ren S, Cao Z, Zheng S et al.. Pegylated Interferon Treatment for the Effective Clearance of Hepatitis B Surface Antigen in Inactive HBsAg Carriers: A Meta-Analysis. Frontiers in immunology 2021. link