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[Quantitative analysis of HBV cccDNA from liver biopsy specimens in HBV carriers: correlation with serological makers
Lin Zhang1, Feng Wu, Li-lan Shi
1Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Insights
Hepatitis B virus covalently closed circular DNA (cccDNA) is consistently found in chronic carriers. Serum HBV DNA does not reflect liver cccDNA levels, but HBsAg quantification offers some insight.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Context:
- Chronic Hepatitis B virus (HBV) infection is a global health concern.
- Intrahepatic HBV covalently closed circular DNA (cccDNA) is the template for viral replication and a key factor in disease persistence.
- Understanding the relationship between serum markers and intrahepatic cccDNA is crucial for disease management.
Purpose:
- To investigate the correlation between serum HBV DNA, serological markers, and intrahepatic HBV cccDNA in chronic HBV carriers.
- To determine if serum markers can accurately represent the level of intrahepatic cccDNA.
Summary:
- HBV cccDNA was detected in all chronic HBV carriers, with levels ranging from 3.15 x 10^3 to 1.06 x 10^7 copies/mg of liver tissue.
- A positive correlation was observed between intrahepatic cccDNA and total intrahepatic HBV DNA (r = 0.375, P < 0.05).
- No significant correlation was found between cccDNA and serum HBV DNA (P = 0.174), but a positive correlation existed between cccDNA and serum HBsAg quantification (r = 0.562, P < 0.001).
Impact:
- Serum HBV DNA levels are not indicative of intrahepatic cccDNA levels in chronic HBV carriers.
- Serum HBsAg quantification can serve as a partial surrogate marker for intrahepatic cccDNA levels.
- These findings refine our understanding of HBV persistence and may inform monitoring strategies.
Objective:
To investigate the correlation of sera HBV DNA and serological makers with hepatic tissue HBVcccDNA in chronic HBV carriers.
Methods:
Real time fluorescence quantitative polymerase chain reaction (RT-PCR) were used to detect HBV covalently closed circular DNA (cccDNA) and total intrahepatic HBV DNA from 30 needle-biopsy specimens as well as HBV DNA in sera in chronic HBV carriers. Quantification of the HBsAg, HBeAg in sera were quantified using Chemiluminescence immunoassay.
Results:
HBVcccDNA can be detected in chronic HBV carriers, which rang from 3.15 x 10(3) copies/mg to 1.06 x 10(7) copies/mg. There was a positive correlation between the cccDNA and HBVtDNA (r = 0.375, P < 0.05), but there was no correlation between the cccDNA and sera HBV DNA (P = 0.174). There was a positive correlation between cccDNA and sera HBsAg quantification (r = 0.562, P < 0.001) but no correlation with sera HBeAg qantification (r = 0.152, P > 0.05).
Conclusion:
HBV cccDNA can be replicated stably in hepatic tissue in all chronic HBV carriers. HBV DNA in sera can not be indicated hepatic tissue cccDNA level. While HBsAg quantification in sera can be used as a marker of cccDNA quantification in hepatic tissue to some extent.

