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Updated: Jun 10, 2026

Real-Time Polymerase Chain Reaction-Based Detection and Quantification of Hepatitis B Virus DNA
Published on: December 15, 2023
Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in
L Y Lin1, V W S Wong, H J Zhou
1Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Insights
Serum HBV DNA levels correlate with Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in patients with HBeAg-negative chronic hepatitis B. This finding helps understand viral persistence and disease activity.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is the primary driver of persistent HBV infection.
- Identifying reliable serum markers for intrahepatic cccDNA is crucial for managing HBeAg-negative chronic hepatitis B.
- Understanding the relationship between serum markers and intrahepatic viral activity is key to assessing disease progression.
Purpose of the Study:
- To investigate serum surrogate markers for intrahepatic HBV cccDNA.
- To evaluate intrahepatic viral events in relation to disease activity in HBeAg-negative chronic hepatitis B patients.
- To determine if serum HBV DNA or HBsAg levels correlate with cccDNA and viral replication efficiency.
Main Methods:
- Study included 33 treatment-naïve HBeAg-negative patients with chronic hepatitis B who underwent liver biopsy.
- Active disease was defined by elevated serum alanine aminotransferase (>40 IU/L) and HBV DNA (>10,000 copies/ml).
- Correlations between serum HBV DNA, serum HBsAg, intrahepatic cccDNA, and total intrahepatic HBV DNA were analyzed.
Main Results:
- Serum HBV DNA showed a significant positive correlation with both log cccDNA (r=0.41, P=0.018) and log total intrahepatic HBV DNA (r=0.71, P<0.0001).
- Serum HBsAg did not significantly correlate with log cccDNA (P=0.15) or log total intrahepatic HBV DNA (P=0.97).
- Patients with active disease exhibited significantly higher median log cccDNA and log total intrahepatic HBV DNA levels compared to those with inactive disease.
Conclusions:
- Serum HBV DNA levels serve as a surrogate marker for intrahepatic HBV cccDNA and viral replication efficiency in HBeAg-negative chronic hepatitis B.
- Serum HBsAg levels do not accurately reflect the intrahepatic viral load or cccDNA levels in this patient group.
- These findings highlight the utility of serum HBV DNA in monitoring viral persistence and disease activity.
Abstract:
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/10(6) cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B.
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