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Hepatitis B virus infection

Abstract

Hepatitis B virus (HBV) is a hepatotropic virus that can establish a persistent and chronic infection in humans through immune anergy. Currently, 3.5% of the global population is chronically infected with HBV, although the incidence of HBV infections is decreasing owing to vaccination and, to a lesser extent, the use of antiviral therapy to reduce the viral load of chronically infected individuals. The course of chronic HBV infection typically comprises different clinical phases, each of which potentially lasts for decades. Well-defined and verified serum and liver biopsy diagnostic markers enable the assessment of disease severity, viral replication status, patient risk stratification and treatment decisions. Current therapy includes antiviral agents that directly act on viral replication and immunomodulators, such as interferon therapy. Antiviral agents for HBV include reverse transcriptase inhibitors, which are nucleoside or nucleotide analogues that can profoundly suppress HBV replication but require long-term maintenance therapy. Novel compounds are being actively investigated to achieve the goal of HBV surface antigen seroclearance (functional cure), a serological state that is associated with a higher remission rate (thus, no viral rebound) after treatment cessation and a lower rate of cirrhosis and hepatocellular carcinoma. This Primer addresses several aspects of HBV infection, including epidemiology, immune pathophysiology, diagnosis, prevention and management.

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Figure 1: Hepatitis B virions and subviral particles under electron microscopy.
Figure 2: Global distribution of chronic hepatitis B infection and viral genotypes.
Figure 3: Genomic structure of HBV.
Figure 4: The HBV replication cycle and key viral markers.
Figure 5: HBV-specific immune responses.
Figure 6: Hepatitis B disease phases and treatment indications.
Figure 7: Approved treatment agents for chronic HBV infection.

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Contributions

Introduction (M.-F.Y.); Epidemiology (D.-S.C.); Mechanisms/pathophysiology (S.A.L. and C.-L.L.); Diagnosis, screening and prevention (G.M.D.); Management (C.-L.L., D.T.Y.L., H.L.A.J. and M.G.P.); Quality of life (D.T.Y.L.); Outlook (M.-F.Y.); Overview of Primer (M.-F.Y.).

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Correspondence to Man-Fung Yuen.

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Competing interests

M.-F.Y. has received research grants and/or served as an adviser for AbbVie, Arrowhead Pharmaceuticals, Biocartis, BristolMyers Squibb, Fujirebio, Gilead Sciences, GlaxoSmithKline, LF Asia Limited, Merck Sharp & Dohme, Novartis Pharmaceuticals, Roche Molecular Systems and Sysmex Corporation. D.S.C. has served as an adviser for Bristol-Myers Squibb and Merck Sharp & Dohme. G.M.D. has received research grants and/or served as an adviser for Abbott Laboratories, AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp & Dohme and Transgene. H.L.A.J. has received grants and/or served as consultant for AbbVie, Arbutus, Bristol-Myers Squibb, Gilead Sciences, Janssen, Medimmune, Merck and Roche Molecular Systems. D.T.Y.L. has received research grants from Bristol-Myers Squibb, Gilead Sciences and Roche Molecular Systems and has served as consultant for AbbVie and Gilead Sciences. S.A.L. has served as an adviser and received consulting fees from Arrowhead Pharmaceuticals, AusBio Ltd., Gilead Sciences, Roche Molecular Systems and Janssen and has contract research grants with Arrowhead Pharmaceuticals, Gilead Sciences and Spring Bank Pharmaceuticals, Inc. M.G.P.'s spouse is employed at Hoffman-La Roche. C.-L.L. has received speaker fees from Bristol-Myers Squibb, Gilead Sciences and Novartis and is an advisory board member of Gilead Sciences.

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Yuen, MF., Chen, DS., Dusheiko, G. et al. Hepatitis B virus infection. Nat Rev Dis Primers 4, 18035 (2018). https://doi.org/10.1038/nrdp.2018.35

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