Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells

Abstract

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections account for 57% of cases of liver cirrhosis and 78% of cases of primary liver cancer worldwide and cause a million deaths per year. Although HBV and HCV differ in their genome structures, replication strategies and life cycles, they have common features, including their noncytopathic nature and their capacity to induce chronic liver disease, which is thought to be immune mediated. However, the rate of disease progression from chronic hepatitis to cirrhosis varies greatly among infected individuals, and the factors that regulate it are largely unknown. This review summarizes our current understanding of the roles of antigen-specific and nonspecific immune cells in the pathogenesis of chronic hepatitis B and C and discusses recent findings that identify natural killer cells as regulators of T cell function and liver inflammation.

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Figure 1: Natural history of chronic HBV and HCV infections.
Figure 2: NK cell–mediated lysis of intrahepatic cells involved in the pathogenesis of viral hepatitis.
Figure 3: NK cell–mediated regulation of antiviral T cell responses as observed in the LCMV model of viral hepatitis.
Figure 4: Pathogenesis of HBV-related liver disease.

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Acknowledgements

This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health.

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Correspondence to Barbara Rehermann.

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Rehermann, B. Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells. Nat Med 19, 859–868 (2013). https://doi.org/10.1038/nm.3251

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