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
School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China.
Senior Department of Hepatology, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China.
Hepatol Int. 2025 Jun 18. doi: 10.1007/s12072-025-10823-5.
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.
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.
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.
Novel antiviral treatments showed limited effectiveness in achieving HBsAg loss and reduction, highlighting the need to address identified barriers in future research.
实现慢性乙型肝炎（HBV）的“功能性”治愈是新型抗病毒治疗的主要目标。我们试图评估这些新型治疗的疗效和安全性，并确定实现功能性治愈的新障碍。
我们系统回顾了2018年至2023年的临床试验，从clinicaltrials.gov记录中识别出244项关于HBV的试验。主要结局是随访结束时（EOF）的功能性治愈率。次要结局包括HBsAg水平变化、HBsAg消失率、HBV DNA反弹和不良事件。进行了荟萃分析。
我们对涉及1789例非肝硬化HBV患者的19项研究进行的荟萃分析发现，功能性治愈率极低（0.0%，95%CI 0.0 - 0.4%），HBsAg消失率较低（治疗结束时[EOT]为0.9%，EOF时为0.1%）。EOT时HBsAg水平下降（-0.41 log10 IU/mL，95%CI -0.45至-0.37，p < 0.001），但这种下降在EOF时未持续。20.5%的停药病例发生病毒学复发。尽管新型治疗耐受性良好，但不良事件发生率较高（OR = 1.77，95%CI 1.26 - 2.48）。实现功能性治愈的挑战包括复杂的试验设计和未知的混杂因素。
新型抗病毒治疗在实现HBsAg消失和降低方面效果有限，凸显了在未来研究中解决已识别障碍的必要性。
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