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How to achieve immune control in chronic hepatitis B?

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Abstract

Chronic hepatitis B infection remains a major global health problem despite the existence of an effective vaccine. The current treatment options are either nucleos(t)ide analog therapy, which inhibits viral replication, or peginterferon-α, which has mainly immunomodulatory effects. However, treatment-induced HBeAg seroconversion with suppressed viral replication is mostly not sustainable, and loss of HBsAg is a rarely achieved endpoint. In addition, the hepatitis B virus persists in hepatocytes even after HBsAg clearance as covalently closed circular DNA is not eliminated from the hepatocytes. Because the course of chronic hepatitis B is determined by an ongoing interaction between the virus and the host immune system, immunomodulation may be the most logical approach in attempting to accomplish control or even cure of chronic hepatitis B. In the last years, methods for measuring the degree of immune control have been a major area of interest, with an important role for monitoring of HBsAg levels. In addition, new immunomodulatory agents are being developed and tested, providing promising options for future treatment.

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Abbreviations

ADV:

Adefovirdipivoxil

ALT:

Alanine transaminase

cccDNA:

Covalently closed circular DNA

CHB:

Chronic hepatitis B

DCs:

Dendritic cells

ENH:

HBeAg-negative hepatitis

ETV:

Entecavir

HBsAg:

Hepatitis B surface antigen

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

IA phase:

Immune-active phase

IC:

Inactive carrier

IT phase:

Immune-tolerant phase

IFNα:

Interferon-α

IFNαR:

IFNα-receptor

LTbR:

Lymphotoxin-beta receptor

NA:

Nucleos(t)ide analog

PEG-IFNα:

Peginterferon-α

NKcell:

Natural killer cell

PD:

Programmed death

PEG-IFNλ:

Peginterferon-λ

RNAi:

RNA interference

TDF:

Tenofovir disoproxil fumarate

TLR-7:

Toll-like receptor 7

ZFNs:

Zinc-finger nucleases

ZFPs:

Zinc-finger proteins

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Acknowledgments

Prof.Dr. H.L.A. Janssen received grants from and is a consultant for Bristol Myers Squibb, Gilead Sciences, Novartis, Roche, Merck and Innogenetics.

Compliance with ethical requirements and Conflict of interest

This article does not contain any studies with human or animal subjects. Margo J. H. van Campenhout and Harry L. A. Janssen declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

    Margo J. H. van Campenhout & Harry L. A. Janssen

  2. Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, Canada

    Harry L. A. Janssen

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  1. Margo J. H. van Campenhout
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Correspondence to Harry L. A. Janssen.

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van Campenhout, M.J.H., Janssen, H.L.A. How to achieve immune control in chronic hepatitis B?. Hepatol Int 9, 9–16 (2015). https://doi.org/10.1007/s12072-014-9571-3

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