基因组前的HBV RNA和HBcrAg可以预测在核苷酸类似物疗法抑制下

StephenW

Hepatology. 2019 Nov 7. doi: 10.1002/hep.31026. [Epub ahead of print]
Pre-genomic HBV RNA and HBcrAg predict outcomes in HBeAg negative chronic hepatitis B patients suppressed on nucleos(t)ide analogue therapy.
Carey I1, Gersch J2, Wang B1, Moigboi C1, Kuhns M2, Cloherty G2, Dusheiko G1, Agarwal K1.
Author information

1
    Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom.
2
    Department of Infectious Diseases, Abbott Laboratories, North Chicago, Illinois, United States of America.

Abstract
BACKGROUND AND AIMS:

A dichotomous separation of hepatitis B viral DNA and HBsAg concentrations occurs during the natural history and treatment of chronic hepatitis B. We have evaluated the ability of HBV RNA and HBcrAg as surrogates of silencing of cccDNA, to characterise this dissociation, and virological outcomes.
METHODS:

3 cohorts of HBeAg-negative patients were studied: Cohort A: 66 HBeAg-negative patients on long-term nucleos(t)ide analogue (NA) therapy. Cohort B: 23 anti-HBe positive patients who stopped treatment. Cohort C: 19 anti-HBe-positive patients on long-term NA treatment who achieved HBsAg loss and in whom treatment was withdrawn. The concentrations of HBV serological/virological biomarkers (HBV DNA, HBsAg, HBcrAg, HBV RNA) were measured in sequential samples at different time-points on/off therapy.
RESULTS:

Cohort A: After 3 years of antiviral therapy, 33% and 30% had detectable HBcrAg and HBV RNA respectively, despite all being HBV DNA negative. After 5 years' therapy with NA, 27% and 14% had detectable HBcrAg and HBV RNA. Detectable HBcrAg and HBV RNA at the time of treatment withdrawal was only observed in those patients who developed a severe aminotransferase flare. Only those patients with HBV reactivation in cohort C had detectable HBV RNA at treatment withdrawal, but HBcrAg and HBV DNA were not detected.
CONCLUSION:

HBcrAg and HBV RNA are sensitive biomarkers of continued transcription of cccDNA in HBeAg-negative patients despite marked HBV DNA suppression by NA. These markers were predictors of severe ALT flares, after treatment withdrawal, and HBV DNA reactivation. Their measurement during the natural history of hepatitis B, and on treatment with current and new agents, could characterize residual HBV RNA transcription from cccDNA, and assist new drug development and disease management.

© 2019 by the American Association for the Study of Liver Diseases.
KEYWORDS:

HBcrAg; cccDNA transcription; nucleos(t)ide analogue withdrawal; pre-genomic HBV RNA

PMID:
    31701544
DOI:
    10.1002/hep.31026

StephenW

肝病学。 2019年11月7日.doi：10.1002 / hep.31026。 [Epub提前发布]
基因组前的HBV RNA和HBcrAg可以预测在核苷酸类似物疗法抑制下的HBeAg阴性慢性乙型肝炎患者的预后。
Carey I1，Gersch J2，Wang B1，Moigboi C1，Kuhns M2，Cloherty G2，Dusheiko G1，Agarwal K1。
作者信息

1个
英国伦敦国王学院医院肝病研究所，SE5 9RS。
2
美利坚合众国伊利诺伊州北芝加哥雅培实验室传染病科。

抽象
背景与目的：

在自然病史和慢性乙型肝炎的治疗过程中，发生了乙型肝炎病毒DNA和HBsAg浓度的二分分离。我们评估了HBV RNA和HBcrAg作为cccDNA沉默替代品的能力，以表征这种解离和病毒学结果。
方法：

研究了3组HBeAg阴性患者：A组：66名长期接受核苷酸类似物（NA）治疗的HBeAg阴性患者。队列B：23名停止治疗的抗HBe阳性患者。队列C：19位长期接受NA治疗的抗HBe阳性患者，其HBsAg丢失并已退出治疗。在不同时间点开/关治疗的连续样本中测量HBV血清学/病毒学生物标志物（HBV DNA，HBsAg，HBcrAg，HBV RNA）的浓度。
结果：

队列A：经过3年的抗病毒治疗，尽管HBV DNA均为阴性，但分别有33％和30％的患者可检测到HBcrAg和HBV RNA。用NA治疗5年后，有27％和14％的患者检测出HBcrAg和HBV RNA。停药时仅在发生严重氨基转移酶耀斑的患者中观察到可检测的HBcrAg和HBV RNA。仅在队列C中具有HBV再激活的那些患者在停药时具有可检测到的HBV RNA，但未检测到HBcrAg和HBV DNA。
结论：

尽管NA明显抑制了HBV DNA，但HBcrAg和HBV RNA是HBeAg阴性患者cccDNA继续转录的敏感生物标志物。这些标志物是戒断后和HBV DNA复活后严重ALT发作的预测指标。他们在乙型肝炎自然病史中以及在使用现有药物和新药物治疗后的测量结果可以表征cccDNA中残留的HBV RNA转录，并有助于新药开发和疾病管理。

©2019美国肝病研究协会版权所有。
关键字：

HBcrAg; cccDNA转录；核仁类似物撤离；基因组前HBV RNA

PMID：
31701544
DOI：
10.1002 / hep.31026