HIV-HBV合并感染中血清乙肝核心相关抗原与乙肝病毒肝内总DNA及共价闭合环状DNA病毒载量的相关性

Correlation of serum hepatitis B core-related antigen with hepatitis B virus total intrahepatic DNA and covalently closed circular-DNA viral load in HIV-hepatitis B coinfection.

作者信息

Dezanet Lorenza N C, Maylin Sarah, Gabassi Audrey, Rougier Hayette, Miailhes Patrick, Lascoux-Combe Caroline, Chas Julie, Girard Pierre-Marie, Delaugerre Constance, Zoulim Fabien, Lacombe Karine, Boyd Anders

机构信息

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP.

APHP, Hôpital Saint-Louis, Laboratorie de Virologie.

出版信息

AIDS. 2020 Nov 1;34(13):1943-1949. doi: 10.1097/QAD.0000000000002659.

DOI:10.1097/QAD.0000000000002659

PMID:32773480

Abstract

OBJECTIVE

To assess whether quantified hepatitis B core-related antigen (qHBcrAg) is a surrogate marker of intrahepatic replication in HIV and hepatitis B virus (HBV) coinfection.

DESIGN

Cross-sectional study of 31 HIV-HBV-infected patients (total liver biopsies, n = 38) from a well defined cohort.

METHODS

Spearman's rank correlation coefficients were calculated between qHBcrAg and intrahepatic markers of HBV replication [total intrahepatic-DNA, covalently closed circular (ccc) DNA, cccDNA : total intrahepatic-DNA ratio].

RESULTS

At biopsy, 22 (71.0%) patients were hepatitis B 'e' antigen (HBeAg)-positive, 22 (71.0%) had detectable plasma HBV-DNA, and 17 (54.8%) were treated with tenofovir. Median levels (interquartile range) of intrahepatic markers were as follows: HBV cccDNA (n = 34), 0.26 copies/cell (0.4-2.89); total intrahepatic-DNA (n = 38), 2.38 copies/cell (0.58-207.9), and cccDNA : total intrahepatic-DNA ratio (n = 34), 0.05 (interquartile range = 0.01-0.12). There was a significantly strong correlation between qHBcrAg and cccDNA in all patients (Rho = 0.65, P < 0.001), while a moderate correlation was observed between qHBcrAg and total intrahepatic-DNA (Rho = 0.57, P < 0.001) or cccDNA : total intrahepatic-DNA ratio (Rho = -0.45, P = 0.01). Similar findings were observed for HBeAg-positive patients and those with detectable HBV-DNA, with the exception of qHBcrAg and cccDNA or cccDNA : total intrahepatic-DNA ratio. In contrast, no significant correlation between qHBcrAg and any intrahepatic marker was observed in HBeAg-negative patients or those with undetectable HBV-DNA. No significant difference was observed in median qHBcrAg levels across liver fibrosis stages (P = 0.5).

CONCLUSION

qHBcrAg is a potential surrogate marker of cccDNA in HIV-HBV coinfected patients, yet might be less useful with undetectable serum HBV-DNA or HBeAg-negative status. Whether qHBcrAg provides further clinical utility compared with other serological markers remains debatable.

摘要

目的

评估定量乙型肝炎核心相关抗原（qHBcrAg）是否为HIV与乙型肝炎病毒（HBV）合并感染时肝内复制的替代标志物。

设计

对来自一个明确队列的31例HIV-HBV合并感染患者（共进行了38次肝脏活检）进行横断面研究。

方法

计算qHBcrAg与HBV复制的肝内标志物[肝内总DNA、共价闭合环状（ccc）DNA、cccDNA:肝内总DNA比值]之间的Spearman等级相关系数。

结果

活检时，22例（71.0%）患者乙型肝炎e抗原（HBeAg）阳性，22例（71.0%）患者血浆中可检测到HBV DNA，17例（54.8%）患者接受了替诺福韦治疗。肝内标志物的中位数水平（四分位间距）如下：HBV cccDNA（n = 34），0.26拷贝/细胞（0.4 - 2.89）；肝内总DNA（n = 38），2.38拷贝/细胞（0.58 - 207.9），以及cccDNA:肝内总DNA比值（n = 34），0.05（四分位间距 = 0.01 - 0.12）。所有患者中，qHBcrAg与cccDNA之间存在显著强相关性（Rho = 0.65，P < 0.001），而qHBcrAg与肝内总DNA（Rho = 0.57，P < 0.001）或cccDNA:肝内总DNA比值（Rho = -0.45，P = 0.01）之间存在中度相关性。HBeAg阳性患者和可检测到HBV DNA的患者也观察到类似结果，但qHBcrAg与cccDNA或cccDNA:肝内总DNA比值除外。相比之下，HBeAg阴性患者或HBV DNA检测不到的患者中，未观察到qHBcrAg与任何肝内标志物之间存在显著相关性。不同肝纤维化阶段的qHBcrAg中位数水平无显著差异（P = 0.5）。