HBcrAg与HBeAg阳性慢性乙型肝炎患者的肝内HBV tDNA和cccDNA相关

StephenW

J Clin Microbiol. 2018 Oct 24. pii: JCM.01303-18. doi: 10.1128/JCM.01303-18. [Epub ahead of print]
HBcrAg correlated with intrahepatic HBV tDNA and cccDNA in HBeAg-positive chronic hepatitis B patients.
Wang L1, Cao X1, Wang Z1, Gao Y1, Deng J1, Liu X2, Zhuang H2.
Author information

1
    Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
2
    Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. [email protected] [email protected]).

Abstract

This study was to explore the correlation of serum hepatitis B core-related antigen (HBcrAg) with intrahepatic HBV covalently closed circular DNA (cccDNA) and HBV total DNA (tDNA) in HBeAg-positive chronic hepatitis B (CHB) patients. Serum HBcrAg and other parameters including HBV DNA, HBV RNA, HBeAg, HBsAg, anti-HBc, ALT, AST were quantitatively measured at baseline and follow-up time points. Intrahepatic HBV cccDNA and tDNA were quantitatively detected at baseline and 96-week. Grading of liver necroinflammation and staging of hepatic fibrosis were assessed at baseline and 96-week. Correlations between serum HBcrAg and other parameters were analyzed by Pearson's correlation analysis. The results showed that pre-treatment HBcrAg correlated significantly with HBV tDNA level (r=0.328, P=0.003) in 82 CHB patients, and intrahepatic HBV cccDNA (r=0.323, P=0.004) (n=79) after removing three outliers. Serum HBcrAg correlated better with HBV cccDNA in patients with lower level of serum HBV DNA (stratified by 7 log IU/ml of HBV DNA: r=0.656, P=0.003 vs. r=-0.02, P=0.866). Significant inverse correlations were found between HBcrAg and grade of liver necroinflammation (r=-0.245, P=0.037), stage of hepatic fibrosis (r=-0.360, P=0.002) at baseline. Serum HBcrAg presented significant correlation with intrahepatic HBV cccDNA in patients with HBeAg seroconversion at 96-week (r=0.622, P=0.006). The decline in HBcrAg showed significant correlation with the decline in HBV cccDNA after 96-week NAs therapy (r=0.282, P=0.043). Serum HBcrAg also correlated significantly with other serum markers at baseline and 96-week of NAs therapy. In conclusion, baseline HBcrAg and its declined value were significantly correlated with the corresponding intrahepatic HBV cccDNA.

PMID:
    30355757
DOI:
    10.1128/JCM.01303-18

StephenW

J Clin Microbiol。 2018年10月24日.pii：JCM.01303-18。 doi：10.1128 / JCM.01303-18。 [提前打印]
HBcrAg与HBeAg阳性慢性乙型肝炎患者的肝内HBV tDNA和cccDNA相关。
王丽，曹琦，王梓，高莹，邓瑾，刘曦，庄H2。
作者信息

1
    北京大学医学部基础医学院微生物学与传染病研究中心，北京100191
2
    北京大学医学部基础医学院微生物学与传染病研究中心，北京100191 [email protected] [email protected]）。

抽象

本研究旨在探讨HBeAg阳性慢性乙型肝炎（CHB）患者血清乙型肝炎核心相关抗原（HBcrAg）与肝内HBV共价闭合环状DNA（cccDNA）和HBV总DNA（tDNA）的相关性。在基线和随访时间点定量测定血清HBcrAg和其他参数，包括HBV DNA，HBV RNA，HBeAg，HBsAg，抗HBc，ALT，AST。在基线和96周时定量检测肝内HBV cccDNA和tDNA。在基线和96周评估肝脏坏死性炎症的分级和肝纤维化的分期。通过Pearson相关分析分析血清HBcrAg与其他参数之间的相关性。结果显示，82例CHB患者治疗前HBcrAg与HBV tDNA水平显着相关（r = 0.328，P = 0.003），去除3例异常值后，肝内HBV cccDNA（r = 0.323，P = 0.004）（n = 79） 。在血清HBV DNA水平较低的患者中，血清HBcrAg与HBV cccDNA相关性较好（按7 log IU / ml HBV DNA分层：r = 0.656，P = 0.003，r = -0.02，P = 0.866）。 HBcrAg与肝脏坏死性炎症程度（r = -0.245，P = 0.037），基线时肝纤维化分期（r = -0.360，P = 0.002）之间存在显着的负相关。血清HBcrAg与96周HBeAg血清学转换患者的肝内HBV cccDNA显着相关（r = 0.622，P = 0.006）。在96周的NAs治疗后，HBcrAg的下降与HBV cccDNA的下降显着相关（r = 0.282，P = 0.043）。血清HBcrAg也与其他血清标志物在基线和96周的NAs治疗中显着相关。总之，基线HBcrAg及其下降值与相应的肝内HBV cccDNA显着相关。

结论：
    30355757
DOI：
    10.1128 / JCM.01303-18