乙型肝炎病毒核心相关抗原作为共价闭合环状DNA的替代标记

StephenW

Hepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA
Authors

    First published: 28 January 2017Full publication history
    DOI: 10.1111/liv.13346  View/save citation
    Cited by (CrossRef): 0 articles Check for updates

   
    Funding information

    The Lumipulse hepatitis B core-related antigen assay was supported by Fujirebio Inc., Tokyo, Japan.
    Handling Editor: Stanislas Pol

Abstract
Background & Aims

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a key to viral persistence in chronic hepatitis B infection. Serum hepatitis B core-related antigen (HBcrAg) is a novel marker for HBV disease. We aimed to determine whether HBcrAg could be a surrogate marker for intrahepatic cccDNA.
Methods

Three hundred and five liver biopsies and the corresponding sera collected from 138 nucleos(t)ide analogues-treated patients were analysed. 124 patients had paired liver biopsies at baseline and 1-year post-treatment, and 43 patients had a third biopsy after 6-12 years of treatment. Serum HBcrAg, HBV DNA and hepatitis B surface antigen (HBsAg), and intrahepatic HBV DNA and cccDNA were measured.
Results

HBcrAg strongly correlated with cccDNA (r=.70), intrahepatic total HBV DNA (r=.67) and serum HBV DNA (r=.69; all P<.0001). In the 130 samples with undetectable serum HBV DNA, HBcrAg was detectable in 101 (78%) samples, and HBcrAg levels still correlated positively with cccDNA (r=.42, P<.0001). At ≥6 years of therapy, the median logarithmic reduction in HBcrAg was 2.7 log kU/mL, which was comparable to the magnitude of reduction in cccDNA. Twenty-one patients had undetectable cccDNA after ≥6 years of treatment, in whom 15 (71%) had detectable HBcrAg (range: 1.2-537 kU/mL).
Conclusions

Serum HBcrAg is a reliable surrogate marker for intrahepatic cccDNA. HBcrAg could be a very sensitive marker to reflect the cccDNA content and persistence of disease even with the cccDNA levels below the detection limit of assays.

StephenW

乙型肝炎病毒核心相关抗原作为共价闭合环状DNA的替代标记物
作者

    首次发布：2017年1月28日全面的出版历史
    DOI：10.1111 / liv.13346查看/保存引用
    引用（CrossRef）：0篇文章检查更新

   
    资金信息

    Lumipulse乙型肝炎核心相关抗原测定由Fujirebio Inc.，Tokyo，Japan支持。
    处理编辑：Stanislas Pol

抽象
背景与目标

乙型肝炎病毒（HBV）共价闭合环状DNA（cccDNA）是慢性乙型肝炎病毒持续存在的关键。血清乙型肝炎核心相关抗原（HBcrAg）是HBV疾病的新型标志物。我们旨在确定HBcrAg是否可以是肝内cccDNA的替代标记。
方法

分析了三百五十五个肝活组织检查和从138个核心（t）ide类似物治疗的患者中收集的相应血清。 124例患者在基线和1年治疗后配对肝活组织检查，43例患者在6-12年治疗后进行了第三次活检。检测血清HBcrAg，HBV DNA和乙型肝炎表面抗原（HBsAg），肝内HBV DNA和cccDNA。
结果

HBcrAg与cccDNA（r = .70），肝内总HBV DNA（r = .67）和血清HBV DNA（r = .69;全P <0.0001）密切相关。在130例不可检测的血清HBV DNA样本中，101例（78％）样本中检测到HBcrAg，HBcrAg水平与cccDNA呈正相关（r = .42，P <0.0001）。在≥6年的治疗中，HBcrAg的中位数对数降低为2.7log kU / mL，与cccDNA的降低幅度相当。治疗≥6年后，21例患者无法检出cccDNA，其中15例（71％）检出HBcrAg（范围：1.2-537 kU / mL）。
结论

血清HBcrAg是肝内cccDNA的可靠替代标记物。即使cccDNA水平低于测定检测限，HBcrAg也可以是反映cccDNA含量和疾病持续性的非常敏感的标记物。