慢性乙型肝炎感染中HBV表面抗原相关终点的动力学：系统评

StephenW

Dynamics of HBV Surface Antigen Related Endpoints in Chronic Hepatitis B Infection: A Systematic Review and Meta-Analysis
Yusi Chen  1   2 , Justin Jinhui Li  3 , Rong Chen  4   5 , Gailing Li  6 , Jia Ji  6
Affiliations
Affiliations

    1
    School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
    2
    Present address: Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
    3
    Clinical Biostatistics, Janssen R&D, La Jolla, CA, USA.
    4
    School of Pharmaceutical Sciences, Peking University, Beijing, China.
    5
    Present address: Center for Drug Evaluation, National Medical Products Administration, Beijing, China.
    6
    Clinical Pharmacology and Pharmacometrics, Janssen China R&D, Beijing, China.

    PMID: 32609658 DOI: 10.3851/IMP3366

Abstract

Background: In chronic hepatitis B (CHB) treatment, hepatitis B virus surface antigen (HBsAg) is regarded as a promising clinical endpoint associated with long-term clinical outcomes. We performed a meta-analysis to characterize the dynamics and influencing factors of HBsAg.

Methods: Literature search was conducted through PubMed from January 1995 to May 2015 for papers reporting HBsAg in patients receiving various anti-viral treatments. We conducted weighted linear regression to select for potential influencing factors on maximum HBsAg loss percentage, and subgroup analysis to calculate the pooled estimates of maximum HBsAg loss and seroconversion percentage following treatment of interferon (IFN), nucleoside analogue (NUC), or combination therapies (NUC+IFN), respectively. Study heterogeneity was assessed through sensitivity test and I-square statistics.

Results: We collected data from 24 papers involving 6674 adult CHB patients. In most studies, average HBsAg level decreased during treatment but relapsed after treatment cessation, while HBsAg loss or seroconversion percentage continued to increase or remain stable after treatment cessation. No strong relationship was observed between maximum HBsAg change and its baseline level. The pooled estimates of maximum HBsAg loss percentage for IFN (5.3%, 2.7%-7.9%) and NUC+IFN (5.2%, 3.1%-7.4%) were significantly higher than that of NUC (0.93%, 0.29%-1.6%). Higher maximum HBsAg loss percentage is associated with longer peak time. Pooled maximum HBsAg seroconversion percentage estimates were 1.6%, 0.56% and 6.2% for IFN, NUC and NUC+IFN.

Conclusions: With respect to HBsAg lowering, this meta-analysis confirmed the importance of longer treatment duration and addition of IFN, which revealed the potential value of immune-based therapies.

StephenW

慢性乙型肝炎感染中HBV表面抗原相关终点的动力学：系统评价和荟萃分析
陈玉思1 2，贾斯汀金辉李3，陈蓉4 5，盖林李6，贾继6
隶属关系
隶属关系

    1个
    清华大学药学院，北京。
    2
    现在的地址：美国加利福尼亚州圣迭戈市加利福尼亚大学生物科学系。
    3
    临床生物统计学，美国加利福尼亚州拉荷亚，扬森研发中心。
    4
    北京大学药学院，北京。
    5
    现在的地址：中国国家药品监督管理局药品评估中心。
    6
    Janssen中国研发中心，临床药理学和药理学，中国北京。

    PMID：32609658 DOI：10.3851 / IMP3366

抽象

背景：在慢性乙型肝炎（CHB）治疗中，乙型肝炎病毒表面抗原（HBsAg）被视为与长期临床结局相关的有希望的临床终点。我们进行了荟萃分析，以表征HBsAg的动力学和影响因素。

方法：从1995年1月至2015年5月在PubMed上进行文献检索，以检索报告接受各种抗病毒治疗的患者中HBsAg的论文。我们进行了加权线性回归以选择最大HBsAg损失百分比的潜在影响因素，并进行亚组分析以计算干扰素（IFN），核苷类似物（NUC）或联合疗法治疗后最大HBsAg损失和血清转化百分比的合并估计值（ NUC + IFN）。研究的异质性通过敏感性测试和I平方统计进行评估。

结果：我们收集了24篇涉及6674名成人CHB患者的论文的数据。在大多数研究中，平均HBsAg水平在治疗期间下降，但在停药后复发，而HBsAg丢失或血清转化百分比在停药后继续增加或保持稳定。在最大HBsAg变化与其基线水平之间未观察到强烈关系。 IFN（5.3％，2.7％-7.9％）和NUC + IFN（5.2％，3.1％-7.4％）的最大HBsAg损失百分比的汇总估计值明显高于NUC（0.93％，0.29％-1.6％） ）。最大HBsAg损失百分比越高，峰值时间越长。对于IFN，NUC和NUC + IFN，合并的最大HBsAg血清转换百分比估计为1.6％，0.56％和6.2％。

结论：关于降低HBsAg，这项荟萃分析证实了延长治疗时间和添加IFN的重要性，这揭示了基于免疫疗法的潜在价值。