乙肝核心相关抗原水平预测HBeAg阳性慢性乙型肝炎的聚乙二醇

StephenW

Hepatitis B core-related antigen levels predict pegylated interferon-α therapy response in HBeAg-positive chronic hepatitis B
Boris Jb Beudeker  1   2 , Zwier Ma Groothuismink  1 , Robert A de Man  1 , Harry LA Janssen  1   3 , Annemiek A van der Eijk  2 , Andre Boonstra  1 , Milan J Sonneveld  1
Affiliations
Affiliations

    1
    Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
    2
    Department of Viroscience, Erasmus University Medical Center, Rotterdam, the Netherlands.
    3
    Toronto Center for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.

    PMID: 32744512 DOI: 10.3851/IMP3367

Abstract

Background: Serum hepatitis B core-related antigen (HBcrAg) levels reflect intrahepatic hepatitis B virus (HBV) replication activity. We aimed to study whether HBcrAg levels predict response to peginterferon (PEG-IFN) treatment in HBeAg positive chronic hepatitis B (CHB) patients.

Methods: We studied HBcrAg levels in 222 HBeAg-positive patients treated with PEG-IFN with or without lamivudine for 52 weeks in a global randomized trial and compared kinetics across treatment arms and types of response. Optimal HBcrAg cut-offs for stopping therapy were compared to and combined with the currently recommended HBsAg-based stopping-rules.

Results: Baseline HBcrAg levels could not discriminate between responders and non-responders (p=0.91). HBcrAg levels of patients responding to PEG-IFN therapy showed a more pronounced on-treatment decline (mean declines 3.4 vs 1.0 log U/mL; p<0.0001), which was sustained until the end of follow-up (mean declines week 3.8 vs. 1.0 log U/mL; p<0.0001). In the PEG-IFN monotherapy group, HBcrAg levels of >8.35 log U/mL at week 24 identified 19 patients (19%) of whom 1 (NPV=95%) achieved a response. The performance of this HBcrAg-based stopping rule alone was not superior to the one based on HBsAg >20,000 IU/mL. Among patients with an HBsAg <20,000 (n=56), 9 (16%) had an HBcrAg >8.35, of whom 8 achieved no response (NPV 89%).

Conclusions: HBeAg-positive CHB patients with a response to PEG-IFN therapy achieve a more pronounced HBcrAg decline. HBcrAg levels at week 24 of therapy could be used to identify non-responders in combination with the established HBsAg based stopping-rules.

StephenW

乙肝核心相关抗原水平预测HBeAg阳性慢性乙型肝炎的聚乙二醇化干扰素-α治疗反应
Boris Jb Beudeker 1 2，Zwier Ma Groothuismink 1，Robert A de Man 1，Harry LA Janssen 1 3，Annemiek A van der Eijk 2，Andre Boonstra 1，Milan J Sonneveld 1
隶属关系
隶属关系

    1个
    荷兰鹿特丹伊拉斯姆斯大学医学中心胃肠病学和肝病学系。
    2
    荷兰鹿特丹伊拉斯姆斯大学医学中心病毒学系。
    3
    加拿大安大略省多伦多大学健康网络多伦多总医院多伦多肝病中心。

    PMID：32744512 DOI：10.3851 / IMP3367

抽象

背景：血清乙肝核心相关抗原（HBcrAg）水平反映了肝内乙肝病毒（HBV）复制活性。我们旨在研究HBcrAg水平是否可预测HBeAg阳性慢性乙型肝炎（CHB）患者对聚乙二醇干扰素（PEG-IFN）治疗的反应。

方法：我们在一项全球随机试验中研究了222例接受或不接受拉米夫定的PEG-IFN治疗的HBeAg阳性患者的HBcrAg水平，为期52周，并比较了各治疗组的动力学和反应类型。将停止治疗的最佳HBcrAg临界值与当前推荐的基于HBsAg的停止规则进行了比较，并结合使用。

结果：基线HBcrAg水平无法区分反应者和非反应者（p = 0.91）。对PEG-IFN治疗有反应的患者的HBcrAg水平显示出较明显的治疗中下降（平均下降3.4 vs 1.0 log U / mL； p <0.0001），一直持续到随访结束（平均下降3.8周vs. 1.0 log U / mL; p <0.0001）。在PEG-IFN单药治疗组中，第24周的HBcrAg水平> 8.35 log U / mL，确定了19例患者（19％），其中1例（NPV = 95％）获得了缓解。仅基于HBcrAg的停药规则的表现并不优于基于HBsAg> 20,000 IU / mL的停药规则。在HBsAg <20,000（n = 56）的患者中，有9（16％）的HBcrAg> 8.35，其中8例无反应（NPV 89％）。

结论：对PEG-IFN治疗有反应的HBeAg阳性CHB患者实现了更明显的HBcrAg下降。治疗第24周时的HBcrAg水平可与已建立的基于HBsAg的停止规则结合起来用于确定无反应者。