血清HBV DNA加RNA在反映初治HBV感染个体的肝内cccDNA活性方面显

StephenW

J Clin Virol. 2018 Jan 6;99-100:71-78. doi: 10.1016/j.jcv.2017.12.016. [Epub ahead of print]
Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naïve HBV-infected individuals.Huang H1, Wang J2, Li W3, Chen R2, Chen X2, Zhang F4, Xu D5, Lu F6.
Author information
1Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China; Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.2Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China.3Department of clinical laboratory, Beijing Ditan Hospital Capital Medical University, Beijing, China.4Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China. Electronic address: [email protected].5Institute of Infectious Disease and Medical center for Liver Failure, Beijing 302 Hospital, Beijing, China. Electronic address: [email protected].6Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China. Electronic address: [email protected].

AbstractBACKGROUND: Both serum hepatitis B virus (HBV) DNA and RNA can reflect intrahepatic covalently closed circular DNA (cccDNA) activity. However, correlations among viral markers haven't been fully explored.
OBJECTIVES: Here we investigated the correlations between serum HBV RNA and other viral markers in acute hepatitis B patients and treatment-naïve chronic HBV-infected individuals.
STUDY DESIGN: The serum viral markers of 19 acute hepatitis B patients and 84 treatment-naïve chronic HBV-infected individuals at different infection stages were quantified. Correlations among viral markers were analyzed by Pearson's or Spearman's correlation analysis.
RESULTS: Serum viral markers and intrahepatic cccDNA levels were lower in acute hepatitis B patients than in treatment-naïve chronic HBV-infected individuals. Serum HBV RNA levels were positively correlated with serum HBV DNA, HBsAg and intrahepatic cccDNA levels in HBeAg-positive chronic HBV-infected individuals. Total serum HBV nucleic acids (HBV DNA plus RNA) showed superiority in reflecting intrahepatic cccDNA activity. Stratified analysis revealed that such correlations were only found in HBeAg-positive chronic hepatitis B phase. Moreover, high-frequency R193M and P196A mutations were found in the RT region of HBV polymerase leading to lower serum HBV DNA and higher serum HBV RNA levels in HBeAg-negative chronic HBV infection phase.
CONCLUSIONS: HBV replication capability was lower in acute hepatitis B patients than in chronic HBV-infected individuals. In treatment-naïve HBeAg-positive chronic HBV-infected individuals, serum HBV DNA plus RNA showed superiority in reflecting intrahepatic cccDNA activity than each alone. Moreover, mutated RT region of HBV polymerase might lead to the attenuated reverse transcriptional activity of HBV polymerase in HBeAg-negative chronic HBV infection phase.

Copyright © 2018 Elsevier B.V. All rights reserved.

KEYWORDS: Covalently closed circular DNA; Hepatitis B e antigen; Hepatitis B surface antigen; Hepatitis B virus; Pregenomic RNA

PMID:29353073DOI:10.1016/j.jcv.2017.12.016

StephenW

J临床病毒学杂志2018年1月6日; 99：100：71-78。 doi：10.1016 / j.jcv.2017.12.016。 [电子版提前打印]
血清HBV DNA加RNA在反映初治HBV感染个体的肝内cccDNA活性方面显示出优越性。
Huang H1，Wang J2，Li W3，Chen R2，Chen X2，Zhang F4，Xu D5，Lu F6。
作者信息

1
    北京大学医学部微生物与传染病中心，北京;哈尔滨医科大学微生物系，黑龙江哈尔滨。
2
    北京大学医学部微生物与传染病中心，北京，中国。
3
    首都医科大学附属北京地坛医院检验科，北京。
4
    哈尔滨医科大学微生物系，黑龙江哈尔滨。电子地址：[email protected]。
五
    北京302医院传染病与肝病医疗中心。电子地址：[email protected]。
6
    北京大学医学部微生物与传染病中心，北京，中国。电子地址：[email protected]。

抽象
背景：

血清乙型肝炎病毒（HBV）DNA和RNA均能反映肝内共价闭合环状DNA（cccDNA）的活性。然而，病毒标记之间的相关性还没有被充分探索。
目的：

在这里，我们调查了血清HBV RNA和其他病毒标志物在急性乙型肝炎患者和初治慢性HBV感染者之间的相关性。
学习规划：

对19例急性乙型肝炎患者和84例初治慢性HBV感染者在不同感染阶段的血清病毒标志物进行定量。通过皮尔逊（Pearson）或斯皮尔曼（Spearman）相关分析来分析病毒标记之间的相关性。
结果：

急性乙型肝炎患者的血清病毒标志物和肝内cccDNA水平低于未治疗的慢性HBV感染者。血清HBV RNA水平与HBeAg阳性慢性HBV感染者血清HBV DNA，HBsAg和肝内cccDNA水平呈正相关。总血清HBV核酸（HBV DNA加RNA）显示反映肝内cccDNA活性的优越性。分层分析显示，这种相关性仅在HBeAg阳性的慢性乙型肝炎期发现。此外，在HBV聚合酶的RT区发现高频R193M和P196A突变，导致HBeAg阴性慢性HBV感染期中血清HBV DNA降低和血清HBV RNA水平升高。
结论：

急性乙型肝炎患者HBV复制能力低于慢性HBV感染者。在未经治疗的HBeAg阳性的慢性HBV感染者中，血清HBV DNA加RNA显示出反映肝内cccDNA活性的优势。此外，HBV聚合酶的突变RT区可能导致HBV聚合酶在HBeAg阴性慢性HBV感染阶段的逆转录活性减弱。

版权所有©2018 Elsevier B.V.保留所有权利。
关键词：

共价闭合环状DNA;乙肝e抗原;乙型肝炎表面抗原;乙型肝炎病毒;前基因组RNA

结论：
    29353073
DOI：
    10.1016 / j.jcv.2017.12.016