The natural history and the staging of chronic hepatitis B: time for reevaluation of the virus-host relationship based on molecular virology and immunopathogenesis considerations?

Alex J V Thompson, Stephen Locarnini, Kumar Visvanathan

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19 Citations (Scopus)


Hepatitis B is a disease with both virologic and immunologic components. The 2 key virologic events in the life cycle of the hepatitis B virus (HBV) are the generation from genomic DNA of the covalently closed circular (ccc) DNA transcriptional template and reverse transcription of the viral pregenomic (pg) RNA to form the HBV DNA genome. Because the virus utilizes reverse transcription to copy its genome, mutant viral genomes, or quasispecies, are frequently found in the blood of HBV-infected patients. Not surprisingly then, a number of immune escape mutants of HBV are selected out as dominant populations during this response within the term of the natural history of the disease. Human HBV is a highly evolved pathogen and under normal circumstances viral infection and subsequent replication within hepatocytes is not cytopathic. The liver damage associated with acute or chronic hepatitis B (CHB) occurs mainly as a result of attempts, usually unsuccessful, by the host?s immune response to clear HBV from infected hepatocytes1 as part of the ?immuno-elimination? phase of the disease.
Original languageEnglish
Pages (from-to)1031 - 1035
Number of pages5
Issue number3
Publication statusPublished - 2007

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