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Hepatitis B Virus: Persistence and Clearance

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Hepatitis B Virus in Human Diseases

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

Hepatitis B virus (HBV) replicates without killing infected hepatocytes or causing a prolonged activation of innate immunity in vivo. Transient infections can be cleared by the adaptive immune response even after infection has spread to the entire hepatocyte population. Resolution of transient infections requires weeks and is associated with killing of a major fraction of infected hepatocytes by cytotoxic T lymphocytes (CTLs). Cytokines also play a major role, clearing viral DNA replication intermediates from the cytoplasm of infected hepatocytes. A major issue concerns the clearance of covalently closed circular (ccc) DNA, the nuclear transcriptional template of the virus. If clearance is not achieved, infections become chronic, resulting in accelerated turnover of hepatocytes due to an ongoing CTL response. Because hepatocytes appear to form a closed self-renewing population, natural and, especially, CTL-stimulated turnover should lead to genetic narrowing of the hepatocyte population as the patient ages. This process will be further accelerated if any hepatocyte mutations facilitate escape from antiviral CTLs, or provide a growth advantage. Finally, the association of genetic narrowing and expansion of cell clones in the context of chronic liver disease may contribute to the development of hepatocellular carcinoma (HCC), the most serious sequela of chronic hepatitis B.

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Authors and Affiliations

  1. Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA

    Christoph Seeger, Samuel Litwin & William S. Mason

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  1. Christoph Seeger
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  2. Samuel Litwin
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  3. William S. Mason
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Correspondence to Christoph Seeger .

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Editors and Affiliations

  1. Chang Gung University, Chang Gung Memorial Hospital, Taipei, Taiwan

    Yun-Fan Liaw

  2. INSERM Unit 1052, Hospices Civils de Lyon, Lyon University, Lyon, France

    Fabien Zoulim

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Seeger, C., Litwin, S., Mason, W.S. (2016). Hepatitis B Virus: Persistence and Clearance. In: Liaw, YF., Zoulim, F. (eds) Hepatitis B Virus in Human Diseases. Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-22330-8_6

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  • DOI: https://doi.org/10.1007/978-3-319-22330-8_6

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