Hepatitis surface B antigen clearance induced by long-term tenofovir disoproxil fumarate monotherapy in chronic hepatitis B treatment: a meta-analysis and longitudinal modeling analysis

• Published in: Virology journal Vol. 22; no. 1; p. 158
• Main Authors: Jian, Weizhe, Yin, Yalin, Xue, Junsheng, Chen, Rong, Feng, Jingwen, Zeng, Jiayao, He, Ruoyi, Zhou, Tianyan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.05.2025; BMC
• Subjects: Antigens; Antiviral Agents - therapeutic use; CHB; chronic hepatitis B; DNA; Dosage and administration; Drug therapy; fumarates; HBsAg clearance; HBsAg seroconversion; Hepatitis B; hepatitis B antigens; Hepatitis B Surface Antigens - blood; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - immunology; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; Humans; Immune response; Longitudinal Studies; Medical research; Medicine, Experimental; meta-analysis; Model-based simulation; Physiological aspects; seroconversion; simulation models; systematic review; TDF; Tenofovir; Tenofovir - therapeutic use; therapeutics; Treatment Outcome; China; HBsAg clearance; Model-based simulation; CHB; HBsAg seroconversion; TDF
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/s12985-025-02788-6

Chronic hepatitis B (CHB) is a significant global health challenge, with tenofovir disoproxil fumarate (TDF) widely used as an effective treatment option. Despite TDF's efficacy in suppressing hepatitis B virus (HBV) DNA, it rarely achieves functional cure, requiring hepatitis B surface antigen (HBsAg) clearance or seroconversion, which are an optimal goal of CHB treatment. This study aimed to evaluate the long-term effects of TDF monotherapy on HBsAg clearance rates through a systematic review and meta-analysis, combined with a longitudinal modeling analysis to investigate HBsAg dynamics. Eligible studies published between January 1st, 2008, and September 28th, 2023, in PubMed, EMBASE, and Web of Science were included in the systematic review and meta-analysis. The longitudinal model was developed based on data from 123 subjects in a Phase III trial cohort. Twenty-three studies were selected for meta-analysis. The summarized HBsAg clearance rate was near zero and unlikely to increase with extended treatment. The longitudinal model of HBsAg dynamic in CHB patients receiving TDF monotherapy showed a good fitting performance and extrapolation predictive ability. Model-based simulation confirmed that HBsAg clearance remained unlikely with prolonged therapy, with median HBsAg levels reducing by 21% after 168 weeks. The consistency between meta-analysis and model simulation outcomes indicated that TDF monotherapy can achieve a limited reduction in HBsAg levels but did not result in functional cure, which reinforced the limited role of TDF monotherapy in comprehensive CHB management.