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血清乙型肝炎病毒rna预测HBeAg阳性慢性乙型肝炎对聚乙二醇干 [复制链接]

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发表于 2020-2-15 13:23 |只看该作者 |倒序浏览 |打印
J Viral Hepat. 2020 Feb 12. doi: 10.1111/jvh.13272. [Epub ahead of print]
Serum hepatitis B virus rna predicts response to peginterferon treatment in HBeAg-positive chronic hepatitis B.
van Campenhout MJH1, van Bömmel F2, Pfefferkorn M2, Fischer J2, Deichsel D2, Boonstra A1, van Vuuren AJ1, Berg T2, Hansen BE1,3,4, Janssen HLA1,4.
Author information

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

Abstract

Hepatitis B virus (HBV) RNA in serum is a novel biomarker that reflectscccDNA activity. We investigated whether HBV RNA can predict serological response to peginterferon (PEG-IFN) treatment.Serum HBV RNA levels were retrospectively measured at weeks 0, 12, 24, and 52 of therapy and after treatment discontinuation (week 78) in 266 HBeAg-positive chronic HBV patients who had participated in a global randomized controlled trial (HBV99-01 study). Patients received 52 weeks PEG-IFN monotherapy (n=136) orPEG-IFN and lamivudine (n=130). The primary endpoint was HBeAg loss 24 weeks after PEG-IFN discontinuation. At baseline, the mean serum level of HBV RNA was 6.8 (SD 1.2) log c/mL. HBV RNA levels declined to 4.7 (1.7) log c/mL after one year of PEG-IFN therapy alone and to 3.3 (1.2)log c/mL after combination therapy. From week 12 onward, HBV RNA level was significantly lower in patients who achieved HBeAg loss at the end of follow-up as compared to those who did not, regardless of treatment allocation (week 12: 4.4 vs. 5.1 log c/mL, p=0.01; week 24: 3.7 vs. 4.9 log c/mL, p<0.001). The performance of a multivariable model based on HBV RNA level was comparable at week 12 (AUC 0.68)and 24 (AUC 0.72) of therapy. HBV RNA level above 5.5 log c/mL at week 12 showed negative predictive values of 93/67/90/64% for HBV genotypes A/B/C/D for the prediction of HBeAg loss. In conclusion, HBV RNA in serum declines profoundly during PEG-IFN treatment. Early on-treatment HBV RNA level may be used to predict non-response.

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

Chronic hepatitis B infection; Functional cure; Peginterferon treatment; Serum marker; Treatment response

PMID:
    32052503
DOI:
    10.1111/jvh.13272

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30437 
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发表于 2020-2-15 13:23 |只看该作者
J病毒性肝炎。 2020年2月12日。doi:10.1111 / jvh.13272。 [Epub提前发行]
血清乙型肝炎病毒rna预测HBeAg阳性慢性乙型肝炎对聚乙二醇干扰素治疗的反应。
van Campenhout MJH1,vanBömmelF2,Pfefferkorn M2,Fischer J2,Deichsel D2,Boonstra A1,van Vuuren AJ1,Berg T2,Hansen BE1、3、4,Janssen HLA1,4。
作者信息

1个
    荷兰鹿特丹伊拉斯姆斯MC大学医学中心胃肠病学和肝病学系。
2
    莱比锡大学医院,消化科和风湿病科,肝病科,德国莱比锡。
3
    多伦多大学卫生政策,管理与评估研究所。
4
    加拿大多伦多大学健康网多伦多西部和综合医院多伦多肝病中心。

抽象

血清中的乙型肝炎病毒(HBV)RNA是反映cccDNA活性的新型生物标记。我们调查了HBV RNA是否可以预测对聚乙二醇干扰素(PEG-IFN)治疗的血清学反应。在266例HBeAg阳性患者中,在治疗的第0、12、24和52周以及停药后(第78周)回顾性测量了血清HBV RNA水平。参加了一项全球随机对照试验(HBV99-01研究)的慢性HBV患者。患者接受52周的PEG-IFN单药治疗(n = 136)或PEG-IFN和拉米夫定(n = 130)。主要终点是停用PEG-IFN 24周后HBeAg丢失。在基线时,HBV RNA的平均血清水平为6.8(SD 1.2)log c / mL。单独使用PEG-IFN治疗一年后,HBV RNA水平下降至4.7(1.7)log c / mL,联合治疗后下降至3.3(1.2)log c / mL。从第12周开始,无论治疗分配如何,随访结束时实现HBeAg丢失的患者的HBV RNA水平均显着低于未接受治疗的患者(第12周:4.4 vs. 5.1 log c / mL,p = 0.01;第24周:3.7 vs. 4.9 log c / mL,p <0.001)。在治疗的第12周(AUC 0.68)和24周(AUC 0.72),基于HBV RNA水平的多变量模型的性能相当。在第12周时,高于5.5 log c / mL的HBV RNA水平显示A / B / C / D HBV基因型对HBeAg丢失的预测为93/67/90/64%的阴性预测值。总之,在PEG-IFN治疗期间,血清中的HBV RNA急剧下降。早期治疗中的HBV RNA水平可用于预测无反应。

本文受版权保护。版权所有。
关键字:

慢性乙型肝炎感染;功能性治疗;聚乙二醇干扰素治疗;血清标志物;治疗反应

PMID:
    32052503
DOI:
    10.1111 / jvh.13272
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