Functional cure with new antiviral therapy for hepatitis B virus: a systematic review and meta-analysis
Issued Date
2025-01-01
Resource Type
ISSN
19360533
eISSN
19360541
Scopus ID
2-s2.0-105008235460
Journal Title
Hepatology International
Rights Holder(s)
SCOPUS
Bibliographic Citation
Hepatology International (2025)
Suggested Citation
Chen J., Ji D., Jia J., Zhuang H., Zhang X., Wang F.S., Zhang W., Dou X., Tanwandee T., Sarin S.K., Maiwall R., Kumar M., Goh G.B.B., Ghazinyan H., Chutaputti A., Chen P.J., You H., Yu M.L., George J., Omata M., Wang G.Q., Lau G., APASL Viral Elimination Taskforce Functional cure with new antiviral therapy for hepatitis B virus: a systematic review and meta-analysis. Hepatology International (2025). doi:10.1007/s12072-025-10823-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/110867
Title
Functional cure with new antiviral therapy for hepatitis B virus: a systematic review and meta-analysis
Author's Affiliation
The University of Sydney
Fudan University
National Taiwan University
China Medical University Shenyang
General Hospital of People's Liberation Army
Peking University Health Science Center
Ruijin Hospital
Singapore General Hospital
Peking University First Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Siriraj Hospital
Beijing Friendship Hospital, Capital Medical University
Chinese University of Hong Kong, Faculty of Medicine
Phramongkutklao College of Medicine
Institute of Liver and Biliary Sciences
Peking University International Hospital
Humanity and Health Clinical Trial Center
Yerevan Medical Scientific Center
Yamanashi Hospitals (Central and Kita) Organization
Fudan University
National Taiwan University
China Medical University Shenyang
General Hospital of People's Liberation Army
Peking University Health Science Center
Ruijin Hospital
Singapore General Hospital
Peking University First Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Siriraj Hospital
Beijing Friendship Hospital, Capital Medical University
Chinese University of Hong Kong, Faculty of Medicine
Phramongkutklao College of Medicine
Institute of Liver and Biliary Sciences
Peking University International Hospital
Humanity and Health Clinical Trial Center
Yerevan Medical Scientific Center
Yamanashi Hospitals (Central and Kita) Organization
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Achieving a “functional” cure for chronic hepatitis B (HBV) is primary goal for novel antiviral treatments. We sought to evaluate efficacy and safety of these novel treatments and identified emerging barriers to achieving a functional cure. Approach: We systematically reviewed clinical trials from 2018 to 2023, identifying 244 trials from clinicaltrials.gov records on HBV. The primary outcome was functional cure rate at the end of follow-up (EOF). Secondary outcomes included changes in HBsAg levels, HBsAg loss rates, HBV DNA rebound, and adverse events. Meta-analysis was performed. Results: Our meta-analysis of 19 studies involving 1789 non-cirrhotic HBV patients found a minimal functional cure rate (0.0%, 95%CI 0.0–0.4%) and low HBsAg loss rates (0.9% at the end of treatment [EOT] and 0.1% at EOF). HBsAg levels declined at EOT (−0.41 log10 IU/mL, 95%CI −0.45 to −0.37, p < 0.001) but this reduction was not sustained to EOF. Virological relapse occurred in 20.5% of cases off-treatment. Although novel treatments were well-tolerated, they had higher adverse event rates (OR = 1.77, 95%CI 1.26–2.48). Challenges to achieving a functional cure include complex trial designs and unknown confounding factors. Conclusion: Novel antiviral treatments showed limited effectiveness in achieving HBsAg loss and reduction, highlighting the need to address identified barriers in future research.