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.
{"title":"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.","authors":"Weizhe Jian, Yalin Yin, Junsheng Xue, Rong Chen, Jingwen Feng, Jiayao Zeng, Ruoyi He, Tianyan Zhou","doi":"10.1186/s12985-025-02788-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"158"},"PeriodicalIF":4.0000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100987/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virology Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12985-025-02788-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VIROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
背景：慢性乙型肝炎（CHB）是一个重大的全球健康挑战，富马酸替诺福韦二吡酯（TDF）被广泛用作一种有效的治疗选择。尽管TDF具有抑制乙型肝炎病毒（HBV） DNA的功效，但它很少实现功能性治愈，需要清除乙型肝炎表面抗原（HBsAg）或血清转化，而这是治疗乙型肝炎的最佳目标。本研究旨在通过系统回顾和荟萃分析来评估TDF单药治疗对HBsAg清除率的长期影响，并结合纵向建模分析来研究HBsAg动态。方法：将2008年1月1日至2023年9月28日在PubMed、EMBASE和Web of Science上发表的符合条件的研究纳入系统评价和荟萃分析。纵向模型是基于一项III期试验队列中的123名受试者的数据开发的。结果：选取23项研究进行meta分析。总的HBsAg清除率接近于零，并且不太可能随着治疗的延长而增加。慢性乙型肝炎患者接受TDF单药治疗后HBsAg动态的纵向模型具有良好的拟合性能和外推预测能力。基于模型的模拟证实，长期治疗后HBsAg清除仍然不太可能，168周后中位HBsAg水平降低了21%。结论：荟萃分析和模型模拟结果的一致性表明，TDF单药治疗可以实现有限的HBsAg水平降低，但不能实现功能性治愈，这加强了TDF单药治疗在CHB综合治疗中的有限作用。
期刊介绍：
Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies.
The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
