聚乙二醇干扰素α治疗HBeAg阴性慢性乙型肝炎时乙型肝炎核心

StephenW

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J Viral Hepat. 2019 May 28. doi: 10.1111/jvh.13117. [Epub ahead of print]
Hepatitis B core-related antigen monitoring during peginterferon alfa treatment for HBeAg-negative chronic hepatitis B.
van Campenhout MJH1, Rijckborst V1, Brouwer WP1, van Oord GW1, Ferenci P2, Tabak F3, Akdogan M4, Pinarbasi B5, Simon K6, de Knegt RJ1, Boonstra A1, Janssen HLA7, Hansen BE1,7,8.
Author information

1
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
2
    Department of Internal Medicine, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
3
    Cerrahpasa Medical Faculty, Istanbul, Turkey.
4
    Department of Gastroenterology, Yuksek Ihtisas Hospital, Ankara, Turkey.
5
    Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Turkey.
6
    Division of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland.
7
    Toronto Center for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, Canada.
8
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.

Abstract

Serum Hepatitis B core-related antigen (HBcrAg) level moderately correlates with cccDNA. We examined whether HBcrAg can add value in monitoring the effect of peginterferon (PEG-IFN) therapy for HBeAg-negative chronic hepatitis B (CHB) infection. Thus, serum HBcrAg level was measured in 133 HBeAg-negative, mainly Caucasian CHB patients, treated with 48 weeks of PEG-IFN alfa-2a. We assessed its association with response (ALT normalization & HBV DNA <2,000 IU/mL) at week 72. HBcrAg level strongly correlated with HBV DNA level (r=0.8, p<0.001) and weakly with qHBsAg and ALT (both r=0.2, p=0.01). At week 48, mean HBcrAg decline was -3.3 log U/mL. Baseline levels were comparable for patients with and without response at week 72 (5.0 vs. 4.9 log U/mL, p=0.59). HBcrAg decline at week 72 differed between patients with and without response (-2.4 vs. -1.0 log U/mL,p=0.001), but no cut-off could be determined. The pattern of decline in responders resembled that of HBV DNA, but HBcrAg decline was weaker (HBcrAg -2.5 log U/mL; HBV DNA: -4.0 log IU/mL, p<0.001). For early identification of nonresponse, diagnostic accuracy of HBV DNA and qHBsAg decline at week 12 (AUC 0.742, CI-95% [0.0.629-0.855], p<0.001) did not improve by adding HBcrAg decline (AUC 0.747, CI-95% [0.629-0.855] p<0.001), nor by replacing HBV DNA decline by HBcrAg decline (AUC 0.754, CI-95% [0.641-0.867], p<0.001). In conclusion, in Caucasian patients with HBeAg-negative CHB, decline of HBcrAg during PEG-IFN treatment was stronger in patients with treatment response. However, HBcrAg was not superior to HBV DNA and qHBsAg in predicting response during PEG-IFN treatment. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

Antiviral Treatment Response; Biomarker; Hepatitis B; Peginterferon Alfa-2a

PMID:
    31135084
DOI:
    10.1111/jvh.13117

StephenW

J病毒肝病。 2019年5月28日.doi：10.1111 / jvh.13117。 [印刷前的电子版]
聚乙二醇干扰素α治疗HBeAg阴性慢性乙型肝炎时乙型肝炎核心相关抗原监测
van Campenhout MJH1，Rijckborst V1，Brouwer WP1，van Oord GW1，Ferenci P2，Tabak F3，Akdogan M4，Pinarbasi B5，Simon K6，de Knegt RJ1，Boonstra A1，Janssen HLA7，Hansen BE1,7,8。
作者信息

1
    荷兰鹿特丹伊拉斯谟MC大学医学中心消化内科和肝病学系。
2
    维也纳医科大学内科，胃肠病学和肝病学系，维也纳，奥地利。
3
    Cerrahpasa医学院，土耳其伊斯坦布尔。
4
    土耳其安卡拉Yuksek Ihtisas医院消化内科。
五
    土耳其伊斯坦布尔大学伊斯坦布尔医学院内科，胃肠病学科。
6
    波兰弗罗茨瓦夫弗罗茨瓦夫医科大学传染病与肝病学系。
7
    多伦多肝病中心，多伦多西部和综合医院，大学健康网络，加拿大多伦多。
8
    加拿大多伦多大学卫生政策，管理和评估研究所。

抽象

血清乙型肝炎核心相关抗原（HBcrAg）水平与cccDNA中度相关。我们检查了HBcrAg是否可以增加监测聚乙二醇干扰素（PEG-IFN）治疗HBeAg阴性慢性乙型肝炎（CHB）感染的效果。因此，在用48周的PEG-IFNα-2a治疗的133名HBeAg阴性，主要是高加索人CHB患者中测量血清HBcrAg水平。我们在第72周评估了其与反应的关联（ALT正常化和HBV DNA <2,000 IU / mL）.HBcrAg水平与HBV DNA水平强烈相关（r = 0.8，p <0.001），与qHBsAg和ALT（均r = 0.2）呈弱相关，p = 0.01）。在第48周，平均HBcrAg下降为-3.3log U / mL。对于在第72周具有和没有响应的患者，基线水平是相当的（5.0对4.9logU / mL，p = 0.59）。第72周的HBcrAg下降在有和没有反应的患者之间有差异（-2.4对-1.0 log U / mL，p = 0.001），但是没有确定截止值。应答者下降的模式类似于HBV DNA，但HBcrAg下降较弱（HBcrAg -2.5 log U / mL; HBV DNA：-4.0 log IU / mL，p <0.001）。为了早期发现无应答，HBV DNA的诊断准确性和第12周的qHBsAg下降（AUC 0.742，CI-95％[0.0.629-0.855]，p <0.001）并没有因HBcrAg下降而增加（AUC 0.747，CI- 95％[0.629-0.855] p <0.001），也未通过HBcrAg下降取代HBV DNA下降（AUC 0.754，CI-95％[0.641-0.867]，p <0.001）。总之，在患有HBeAg阴性CHB的白种人患者中，PEG-IFN治疗期间HBcrAg的下降在治疗反应的患者中更强。然而，HBcrAg在预测PEG-IFN治疗期间的反应方面并不优于HBV DNA和qHBsAg。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

抗病毒治疗反应;生物标志物;乙型肝炎;聚乙二醇干扰素Alfa-2a

结论：
    31135084
DOI：
    10.1111 / jvh.13117