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标题: 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 [打印本页]

作者: StephenW    时间: 2019-8-7 12:59     标题: 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

Hepatitis B core‐related antigen monitoring during peginterferon alfa treatment for HBeAg‐negative chronic hepatitis B
Margo J. H. van Campenhout
Vincent Rijckborst
Willem Pieter Brouwer
Gertine W. van Oord
Peter Ferenci
Fehmi Tabak
Meral Akdogan
Binnur Pinarbasi
Krzysztof Simon
… See all authors
First published: 28 May 2019
https://doi.org/10.1111/jvh.13117

Funding information:

This work was supported, initiated and sponsored by the Foundation for Liver and Gastrointestinal Research, Rotterdam, the Netherlands. Financial support was provided by Fujirebio Europe, Ghent, Belgium and the Dutch government (Health Holland‐ TKI‐ LSH, [project number LSHM15032]). The studies are part of the Virgo consortium, funded by the Dutch government [project number FES0908]. For the original study, financial support, study medication and drug supply were provided by F. Hoffmann‐La Roche Ltd., Basel, Switzerland. The funding sources did not have any influence on study design, data collection, analysis and interpretation of the data, writing of the report nor the decision to submit for publication.
Sections


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 < 2000 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.
Abbreviations

ALT
    alanine aminotransferase
AUC
    area under the curve
BCP
    basal core promoter
cccDNA
    covalently closed circular DNA
CHB
    chronic hepatitis B infection
CI‐95%
    95% confidence interval
HBcAg
    hepatitis B core antigen
HBcrAg
    Hepatitis B core‐related antigen
HBeAg
    hepatitis B e antigen
HBsAg
    hepatitis B surface antigen
HBV
    hepatitis B virus
LTFU
    long‐term follow‐up
NA(s)
    nucleos(t)ide analogue(s)
p22cr
    22‐kD precore protein
PC
    prescore
PEG‐IFN
    peginterferon
qHBsAg
    quantitative hepatitis B surface antigen
ROC
    receiver operating characteristic
SD
    standard deviation
ULN
    upper limit of normal


作者: StephenW    时间: 2019-8-7 12:59

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的监测
Margo J. H. van Campenhout
Vincent Rijckborst
Willem Pieter Brouwer
Gertine W. van Oord
彼得费伦齐
Fehmi Tabak
Meral Akdogan
Binnur Pinarbasi
Krzysztof Simon
......见所有作者
首次发表:2019年5月28日
https://doi.org/10.1111/jvh.13117

资金信息:

这项工作得到荷兰鹿特丹肝脏和胃肠研究基金会的支持,发起和赞助。 Fujirebio Europe,比利时根特和荷兰政府(Health Holland-TKI-LSH,[项目编号LSHM15032])提供了资金支持。这些研究是荷兰政府资助的Virgo财团的一部分[项目编号FES0908]。对于最初的研究,财务支持,研究药物和药物供应由瑞士巴塞尔的F. Hoffmann-La Roche有限公司提供。资金来源对研究设计,数据收集,数据分析和解释,报告撰写以及提交出版的决定没有任何影响。



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 <2000 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。在第72周,有和没有反应的患者的基线水平相当(5.0 vs 4.9 log U / 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 vs -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)并未因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。
缩略语

ALT
    丙氨酸氨基转移酶
AUC
    曲线下面积
BCP
    基础核心启动子
cccDNA的
    共价闭合环状DNA
CHB
    慢性乙型肝炎感染
CI-95%
    95%置信区间
核心抗原
    乙型肝炎核心抗原
HBcrAg
    乙型肝炎核心相关抗原
大三阳
    乙型肝炎e抗原
乙肝表面抗原
    乙型肝炎表面抗原
HBV
    乙型肝炎病毒
LTFU
    长期随访
NA(S)
    核苷(酸)类似物
p22cr
    22-kD前核蛋白
个人计算机
    prescore
PEG-IFN
    聚乙二醇干扰素
qHBsAg
    定量乙型肝炎表面抗原

    接收器工作特性
SD
    标准差
ULN
    正常上限
作者: StephenW    时间: 2019-8-7 12:59

https://onlinelibrary.wiley.com/doi/full/10.1111/jvh.13117




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