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Updated: May 5, 2026

Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
Active and inactive replication of hepatitis B virus deoxyribonucleic acid in chronic liver disease
Insights
Replicative hepatitis B virus (HBV) forms in the liver are linked to disease activity. Active HBV replication patterns were found in most hepatitis B e antigen-positive patients and some negative patients with advanced liver disease.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- The replicative forms of hepatitis B virus (HBV) in the liver during chronic liver disease remain poorly understood.
- Investigating HBV DNA and its alterations in liver tissue is crucial for understanding disease progression.
Purpose of the Study:
- To analyze HBV DNA and its changes after endonuclease digestion in liver tissues of patients with chronic liver disease.
- To correlate HBV replicative forms with clinical and serological markers.
Main Methods:
- Analysis of HBV DNA and endonuclease digestion patterns in liver tissues from 64 patients.
- Southern blot analysis to resolve episomal replicative forms of HBV.
Main Results:
- An "active" HBV replication pattern was observed in 95% of hepatitis B e antigen-positive patients.
- This active pattern was also present in 19% of hepatitis B e antigen-negative patients with high ALT levels and advanced liver disease.
- An "inactive" episomal viral DNA form was found in patients with mild liver disease and low ALT levels.
Conclusions:
- Episomal replicative forms of HBV can be detected in liver tissue and appear to have clinical significance.
- The presence and form of HBV DNA in the liver correlate with disease activity and severity.
Abstract:
Little is known about the replicative forms of hepatitis B virus (HBV) in the liver in chronic liver disease. We therefore analyzed HBV DNA and the changes in DNA signals after endonuclease digestion in liver tissues taken from 64 patients with hepatitis B surface antigen-positive chronic liver disease. The "active" replication pattern, which included various replicative intermediates, was seen in 36 of 38 (95%) hepatitis B e antigen-seropositive patients. This pattern was also found in 5 of 26 (19%) hepatitis B e antigen-seronegative patients who showed the highest mean serum alanine aminotransferase level (403 +/- 184 mU/ml). Most of them had advanced liver disease. Episomal viral DNA of an "inactive" type having only the supercoiled form was found in 3 patients; they showed the lowest mean serum alanine aminotransferase level (27 +/- 7 mU/ml) and only mild liver disease. As with duck HBV infection, episomal replicative forms of human HBV could be resolved by Southern blot analysis and seem to have clinical implications in human HBV infection.
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