Chronic Hepatitis B Virus Persistence: Mechanisms and Insights.

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.