Functional cure with new antiviral therapy for hepatitis B virus: a systematic review and meta-analysis.
Chen Jing, Ji Dong, Jia Jidong, Zhuang Hui, Zhang Xinxin, Wang Fu-Sheng, Zhang Wenhong, Dou Xiaoguang, Tanwandee Tawesak, Sarin Shiv Kumar, Maiwall Rakhi, Kumar Manoj, Goh George Boon-Bee, Ghazinyan Hasmik, Chutaputti Anuchit, Chen Pei-Jer, You Hong, Yu Ming-Lung, George Jacob, Omata Masao, Wang Gui-Qiang, Lau George, APASL Viral Elimination Taskforce
Hepatology international · 2025 · PMID 40528088 · 인용 16
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.