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Hepatology International

, Volume 9, Issue 1, pp 9–16 | Cite as

How to achieve immune control in chronic hepatitis B?

  • Margo J. H. van Campenhout
  • Harry L. A. JanssenEmail author
Review Article

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.

Keywords

Chronic hepatitis B infection Immune control Hepatitis B surface antigen Covalently closed circular DNA Immune modulation 

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

Notes

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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Copyright information

© Asian Pacific Association for the Study of the Liver 2014

Authors and Affiliations

  • Margo J. H. van Campenhout
    • 1
  • Harry L. A. Janssen
    • 1
    • 2
    Email author
  1. 1.Department of Gastroenterology and HepatologyErasmus MC University Medical Center RotterdamRotterdamThe Netherlands
  2. 2.Toronto Centre for Liver Disease, Toronto Western and General HospitalUniversity Health NetworkTorontoCanada

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