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Review
. 2025 Feb 13;17(2):e78944.
doi: 10.7759/cureus.78944. eCollection 2025 Feb.

Chronic Hepatitis B Virus Persistence: Mechanisms and Insights

Samrita Naidu  1 , Severine Margeridon  2
Affiliations
Review

Chronic Hepatitis B Virus Persistence: Mechanisms and Insights

Samrita Naidu et al. Cureus. .

Abstract

Chronic hepatitis B (CHB) virus infection can lead to severe liver diseases, including cirrhosis and hepatocellular carcinoma. The chronicity of the hepatitis B virus (HBV) occurs because of the persistence of viral covalently closed circular DNA (cccDNA) within hepatocytes. The cccDNA serves as the template for viral replication and is central to HBV, maintaining a viral reservoir within the host. Despite therapeutic advancements, eliminating cccDNA remains elusive due to its evasion of immune surveillance. This review explores the formation and maintenance of cccDNA, highlighting host factors influencing cccDNA stability and viral replication. It also discusses current treatment strategies, including interferon-based therapies and nucleoside/nucleotide analogs, which aim to suppress viral replication. Emerging therapies such as gene editing and molecular interventions hold promise for targeting cccDNA directly. Currently, research is focused on making medications that target host factors of interest to disrupt or clear the viral reservoir. However, future research should focus on innovative approaches that directly target the cccDNA minichromosome, aiming for sustained viral suppression and potentially a cure for the HBV infection.

Keywords: chronic hepatitis b infection; hepatitis b functional cure; hepatitis b infection; hepatitis b virus; viral persistence.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Hepatitis B virion.
HBV: hepatitis B virus; HBeAg: hepatitis B virus E antigen; HBsAg: hepatitis B surface antigen; HBcAg: hepatitis B virus core antigen; rcDNA: relaxed circular DNA.
Figure 2
Figure 2. Replication cycle of cccDNA.
The green strands represent RNA and the black strands represent DNA. The red box highlights the step in which cccDNA is formed from rcDNA. cccDNA: covalently closed circular DNA; rcDNA: relaxed circular DNA; NTCP: sodium taurocholate cotransporting polypeptide; pgRNA: pregenomic RNA; HBV: hepatitis B virus.
Figure 3
Figure 3. CccDNA dilution during mitosis.
The smaller black circles represent cccDNA within the cells. The pink cells are infected while the white cells are uninfected. This demonstrates that as cells divide, the cccDNA reservoir decreases. cccDNA: covalently closed circular DNA.
See this image and copyright information in PMC

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