HBV cccDNA in patients’ sera as an indicator for HBV reactivation and an early signal of liver damage

Chen, Ying; Sze, Johnny; He, Ming‐Liang

doi:10.3748/wjg.v10.i1.82

Cited by 46 publications

(45 citation statements)

References 31 publications

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“…The sensitivity of this assay is higher than reported in other studies, with lower limit of detection ranging between 25 and 100 copies/PCR [He et al, 2002;Jun-Bin et al, 2003;Wong et al, 2004]. However, the observed linearity of this HBV cccDNA assay and the fraction of cccDNA (0.16%) in plasma samples of chronic hepatitis B patients are similar to the results of earlier cccDNA studies [He et al, 2002;Jun-Bin et al, 2003;Chen et al, 2004;Laras et al, 2006]. In addition, the HBV cccDNA assay described here, contains a non-competitive DNA-IC, which makes this cccDNA assay more suitable for clinical use [He et al, 2002;Jun-Bin et al, 2003;Wong et al, 2004].…”

Section: Discussionsupporting

confidence: 34%

Validation of a sensitive and specific real‐time PCR for detection and quantitation of hepatitis B virus covalently closed circular DNA in plasma of chronic hepatitis B patients

Takkenberg

Zaaijer

Molenkamp

et al. 2009

Journal of Medical Virology

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Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) serves as a template for viral replication and plays a role in persistence of HBV infection. The origin and significance of cccDNA in plasma however, is not well understood. A sensitive, specific, and reproducible real-time PCR for detection and quantitation of cccDNA in plasma of chronic hepatitis B patients was developed and validated. Four HBV DNA reference panels, and 96 plasma samples of chronic hepatitis B patients were analyzed. Results were compared with total HBV DNA levels, individual ALT levels and the Histology Activity Index (HAI). This cccDNA assay had a lower limit of detection at 15 copies/PCR, a lower limit of quantitation at 91 copies/PCR and a correlation coefficient (R) of 0.98 (P < 0.0001). cccDNA was detected in two of four international panels. Significant correlation was found between cccDNA and total HBV DNA levels in both panels (R = 0.96, and R = 0.43) and in samples of the chronic hepatitis B patients (R = 0.88, P < 0.0001). In 57% of these samples cccDNA was detectable. Mean level of cccDNA was 0.16% of total HBV load. Plasma cccDNA levels were higher in HBeAg positive samples than in HBeAg negative samples (4.91 log copies/ml vs. 3.88 log copies/ml, P < 0.0001). Levels of total HBV DNA and HBV genotype did not influence cccDNA detection. ALT levels and HAI-score were not correlated with plasma cccDNA levels. These findings suggest that cccDNA levels in plasma are not the result of increased hepatocyte degeneration, but indicate that other mechanisms might be responsible.

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Section: Discussionsupporting

confidence: 34%

Validation of a sensitive and specific real‐time PCR for detection and quantitation of hepatitis B virus covalently closed circular DNA in plasma of chronic hepatitis B patients

Takkenberg

Zaaijer

Molenkamp

et al. 2009

Journal of Medical Virology

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“…After uncoating, HBV was transported to the nucleus, in which the virus would be converted to a covalently closed circular molecule (cccDNA), which would serve as the template for transcription (19). Although HBV is generally considered to be hepatotropic, HBV specific nucleic acids and relative antigen can be detected in many extrahepatic tissues (20,21), and it has been proved that PBMC may be the extrahepatic place of HBV transcription and translation (22,23).…”

Section: Discussionmentioning

confidence: 99%

Influential Factors of Hepatitis B Virus cccDNA in Peripheral Blood Mononuclear Cells Among HBsAg-Positive Pregnant Females Neonates

et al. 2018

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Background: Although many studies have measured HBV cccDNA molecules in Peripheral Blood Mononuclear Cells (PBMC) from patients with active chronic hepatitis B, the current pilot study found PBMC HBV cccDNA in PBMC among HBsAg-positive mothers and their neonates. However, the risk factor of HBV cccDNA in PBMC among HBsAg-positive pregnant female's neonates remains unclear. Objectives: The aim of this study was to explore influential factors of HBV cccDNA in PBMC among HBsAg-positive pregnant female's neonates. Methods: Peripheral blood samples and clinical data were collected from 151 pregnant females, who were positive for hepatitis B surface antigen (HBsAg) in the Third People Hospital of Taiyuan City. Blood samples from 152 neonates were collected before immune prophylaxes administration and tested for HBV markers, HBV DNA in serum, and HBV DNA in PBMC. Bayesian logistic regression with Cauchy prior were used to measure the association between maternal characteristics, neonatal characteristics, and HBV cccDNA in PBMC of neonates. Results: Among neonates of HBsAg-positive mothers, the positive rate of cccDNA in PBMC was 4.61% (7/152). Maternal PBMC HBV cccDNA positivity (OR = 18.411,) and neonates PBMC rcDNA positivity (OR = 13.529, 95% CI: 1.948 -93.690) were associated with HBV cccDNA in neonatal PBMC, respectively. Conclusions: The study suggested that HBV cccDNA can be detected in PBMC of HBsAg-positive mother's neonates. Maternal PBMC HBV cccDNA positivity and neonatal PBMC rcDNA positivity are risk factors of HBV cccDNA in PBMC of neonates.

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“…Our study showed HBV-infected trophoblast cells in vitro, the Color version available online protein as well as regulatory factors required for viral replication, HBsAg concentration, etc., are the factors which promote the success of HBV infection into cultured cells in vitro [23] . HBV covalently closed-loop DNA (cccDNA) is the synthetic template of intermediate mRNA and pregenome RNA in HBV genome replication, and is a key factor which leads to persistent HBV infection [24][25][26][27] . In order to justify the presence of HBV replication in placental trophoblast cells, it is necessary to perform HBV cccDNA detection during the construction of the in vitro HBV-infected trophoblast cell model on which we are currently concluding this corresponding study.…”

Section: Discussionmentioning

confidence: 99%

In vitro Study on Hepatitis B Virus Infecting Human Choriocarcinoma JEG3 Cells and Its Mechanism

Ding

Wang³

et al. 2011

Intervirology

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Aim: To build a hepatitis B virus (HBV)-infected human trophoblast cell model in vitro and determine the mechanism of intrauterine HBV infection. Methods: Serum from hepatitis B-infected patients containing HBV DNA >10⁹ was drawn, subsequently inoculated into human trophoblast cells in vitro (JEG3) and passage-cultured. The supernatants and intracellular HBV viral load of inoculated cells were tested by real-time PCR, and HBV DNA was determined by Southern blot. Results: From inoculation of the 1st passage JEG3 cells, the supernatant viral load of the 1st passage was seen increasing over time, which peaked at 120 h, whereas the HBV viral load was seen decreasing gradually in subsequent passages, and tested negative after the 6th passage. In addition, infected cells of HBV DNA were tested by Southern blot, and showed continual expression in the subsequent cell passages 1–5 while passage 6 was negative. HBsAg was tested as positive from different passages 1–5, and its concentration was also seen decreasing with each subsequent passage cultured until the 6th passage when it tested negative. Conclusion: HBV could infect human trophoblast cells (JEG3) in vitro, and it showed continual expression in subsequent cell passages 1–5.

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HBV cccDNA in patients’ sera as an indicator for HBV reactivation and an early signal of liver damage

Cited by 46 publications

References 31 publications

Validation of a sensitive and specific real‐time PCR for detection and quantitation of hepatitis B virus covalently closed circular DNA in plasma of chronic hepatitis B patients

Validation of a sensitive and specific real‐time PCR for detection and quantitation of hepatitis B virus covalently closed circular DNA in plasma of chronic hepatitis B patients

Influential Factors of Hepatitis B Virus cccDNA in Peripheral Blood Mononuclear Cells Among HBsAg-Positive Pregnant Females Neonates

In vitro Study on Hepatitis B Virus Infecting Human Choriocarcinoma JEG3 Cells and Its Mechanism

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