乙型肝炎病毒RNA下降而病毒抗原没有减少的情况与持续应答

StephenW

Hepatitis B virus RNA decline without concomitant viral antigen decrease is associated with a low probability of sustained response and hepatitis B surface antigen loss
Sylvia M Brakenhoff  1 , Robert A de Man  1 , André Boonstra  1 , Margo J H van Campenhout  1 , Robert J de Knegt  1 , Florian van Bömmel  2 , Annemiek A van der Eijk  3 , Thomas Berg  2 , Bettina E Hansen  4   5 , Harry L A Janssen  4 , Milan J Sonneveld  1
Affiliations
Affiliations

    1
    Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
    2
    Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
    3
    Department of Viroscience, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
    4
    Toronto Center for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, ON, Canada.
    5
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.

    PMID: 33222190 DOI: 10.1111/apt.16172

Abstract

Background: Serum hepatitis B virus (HBV) RNA may reflect intrahepatic HBV replication. Novel anti-viral drugs have shown potent HBV RNA decline without concomitant hepatitis B surface antigen (HBsAg) decrease. How this relates to off-treatment response is yet unclear.

Aim: To study the degree of on-treatment viral antigen decline among patients with pronounced HBV RNA decrease in relation to off-treatment sustained response and HBsAg loss.

Methods: HBV RNA, HBsAg and hepatitis B core-related antigen (HBcrAg) were quantified in patients with chronic hepatitis B who participated in two randomised controlled trials of peginterferon-based therapy. Sustained response (HBV DNA <2000 IU/mL) and/or HBsAg loss were assessed in patients with and without on-treatment HBV RNA response (either >2 log HBV RNA decline or >1 log decline resulting in an undetectable value at on-treatment week 24), stratified by concomitant HBsAg decline (<0.5/0.5-1/>1 log).

Results: We enrolled 279 patients; 176 were hepatitis B e antigen (HBeAg)-positive, and 103 were HBeAg-negative. Sustained response was achieved in 20.4% of patients. At on-treatment week 24, HBV RNA response was associated with higher sustained response rates (27.4% vs 13.0% in non-responders, P = 0.004). However, among patients with an HBV RNA response (n = 135), 56.4% did not experience >0.5 log HBsAg decline. Among HBV RNA responders, sustained response was achieved in 47.6% of those with >1 log HBsAg decline (n = 20/42), vs 16.0% with <0.5 log decline (n = 12/75, P = 0.001). Similar results were obtained with HBcrAg and when response was defined as HBsAg loss.

Conclusions: In this cohort, many patients with HBV RNA response during peginterferon-based treatment did not experience HBsAg and/or HBcrAg decline. The absence of concomitant decline in these viral antigens was associated with low rates of treatment response and HBsAg loss. Future trials should therefore consider kinetics of combined biomarkers to assess anti-viral efficacy. Trial registration, ClinicalTrials.gov: NCT00114361, NCT00146705.

© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

StephenW

乙型肝炎病毒RNA下降而病毒抗原没有减少的情况与持续应答和乙型肝炎表面抗原丢失的可能性低相关
西尔维亚·M·布雷肯霍夫（Sylvia M Brakenhoff）1，罗伯特·阿德曼（Robert A de Man）1，安德烈·邦斯特拉（AndréBoonstra）1，玛格·霍格（Margo JH van Campenhout）1，罗伯特·德·克内格特（Robert J de Knegt）1，弗洛里安·范博默尔（Florian vanBömmel）2，安妮米克·范·范·艾克（Annemiek A van der Eijk）3，托马斯·伯格2，贝蒂娜·汉森（Bettina E Hansen）4 5，哈里洛杉矶詹森4号，米兰·索内维尔德1
隶属关系
隶属关系

    1个
    荷兰鹿特丹大学医学中心，伊拉斯姆斯大学胃肠病学和肝病学系。
    2
    德国莱比锡莱比锡大学医学中心第二医学部肝病科。
    3
    荷兰鹿特丹大学医学中心Erasmus MC病毒科学系。
    4
    多伦多肝病中心，多伦多西部和综合医院，大学健康网，多伦多，加拿大。
    5
    加拿大安大略省多伦多市多伦多大学卫生政策，管理与评估研究所。

    PMID：33222190 DOI：10.1111 / apt.16172

抽象

背景：血清乙型肝炎病毒（HBV）RNA可能反映了肝内HBV复制。新型抗病毒药物显示有效的HBV RNA下降而乙型肝炎表面抗原（HBsAg）却没有下降。目前还不清楚这与脱药反应的关系。

目的：研究与治疗后持续反应和HBsAg丢失有关的HBV RNA明显下降的患者治疗中病毒抗原下降的程度。

方法：参加参与两项基于聚乙二醇干扰素治疗的随机对照试验的慢性乙型肝炎患者，对HBV RNA，HBsAg和乙型肝炎核心相关抗原（HBcrAg）进行定量。在有或没有接受治疗的HBV RNA应答的患者中评估了持续应答（HBV DNA <2000 IU / mL）和/或HBsAg丢失（> 2 log HBV RNA下降或> 1 log下降导致在开启时无法检测到的值） （第24周治疗），并发HBsAg下降（<0.5 / 0.5-1 /> 1 log）分层。

结果：我们招募了279名患者；乙型肝炎e抗原（HBeAg）阳性176例，HBeAg阴性103例。 20.4％的患者实现了持续缓解。在治疗的第24周时，HBV RNA应答与较高的持续应答率相关（27.4％比无应答者13.0％，P = 0.004）。但是，在具有HBV RNA反应（n = 135）的患者中，56.4％的HBsAg下降没有> 0.5 log。在HBV RNA应答者中，HBsAg下降> 1 log（n = 20/42）的患者中有47.6％实现了持续应答，而<0.5 log下降（n = 12/75，P = 0.001）则达到了16.0％。使用HBcrAg以及将响应定义为HBsAg丢失时也获得了相似的结果。

结论：在这个队列中，在以聚乙二醇干扰素为基础的治疗过程中，许多具有HBV RNA反应的患者没有出现HBsAg和/或HBcrAg下降。这些病毒抗原缺乏伴随的下降与治疗反应率低和HBsAg丢失有关。因此，未来的试验应考虑组合生物标志物的动力学，以评估抗病毒功效。试用注册，ClinicalTrials.gov：NCT00114361，NCT00146705。

©2020作者。约翰·威利父子有限公司（John Wiley＆Sons Ltd.）出版的《消化药理学与治疗学》。