18 - World Journal of Gastroenterology

PO Box 2345, Beijing 100023, China World J Gastroenterol 2007 May 14; 13(18): 2554-2567
www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327
wjg@wjgnet.com © 2007 The WJG Press. All rights reserved.
TOPIC HIGHLIGHT
Giuseppe Montalto, Series Editor
Future prospectives for the management of chronic hepatitis B
WF Leemans, HLA Janssen, RA de Man
WF Leemans, HLA Janssen, RA de Man, Department of
Gastroenterology & Hepatology, Erasmus MC, University
Medical Center, Rotterdam, The Netherlands
Correspondence to: RA de Man, MD, PhD, Department of
Gastroenterology and Hepatology, Room H 437, Erasmus MC,
University Medical Center Rotterdam’s-Gravendijkwal 230, 3015
CE Rotterdam, The Netherlands. r.deman@erasmusmc.nl
Telephone: +31-104-635942 Fax: +31-104-365916
Received: 2006-12-15 Accepted: 2007-03-08
Abstract
Chronic hepatitis B virus infection affects about
400 million people around the globe and causes
approximately a million deaths a year. Since the discovery
of interferon-α as a therapeutic option the treatment
of hepatitis B has evolved fast and management has
become increasingly complicated. The amount of viral
replication reflected in the viral load (HBV-DNA) plays
an important role in the development of cirrhosis
and hepatocellular carcinoma. The current treatment
modalities for chronic hepatitis B are immunomodulatory
(interferons) and antiviral suppressants (nucleoside and
nucleotide analogues) all with their own advantages
and limitations. An overview of the treatment efficacy
for both immunomodulatory as antiviral compounds is
provided in order to provide the clinician insight into the
factors influencing treatment outcome. With nucleoside
or nucleotide analogues suppression of viral replication
by 5-7 log10 is feasible, but not all patients respond to
therapy. Known factors influencing treatment outcome
are viral load, ALT levels and compliance. Many other
factors which might influence treatment are scarcely
investigated. Identifying the factors associated with
response might result in stopping rules, so treatment
could be adapted in an early stage to provide adequate
treatment and avoid the development of resistance. The
efficacy of compounds for the treatment of mutant virus
and the cross-resistance is largely unknown. However,
genotypic and phenotypic testing as well as small clinical
trials provided some data on efficacy in this population.
Discontinuation of nucleoside or nucleotide analogues
frequently results in viral relapse; however, some patients
have a sustained response. Data on the risk factors
for relapse are necessary in order to determine when
treatment can be discontinued safely. In conclusion:
chronic hepatitis B has become a treatable disease;
however, much research is needed to tailor therapy to
an individual patient, to predict the sustainability of
response and determine the best treatment for those
www.wjgnet.com
failing treatment.
© 2007 The WJG Press. All rights reserved.
Key words: Hepatitis B virus; Cirrhosis; Treatment;
Interferon; Nucleoside analogues; Nucleotide analogues;
Lamivudine; Adefovir; Entecavir; Telbivudine; Tenofovir;
Resistance; Genotype
Leemans WF, Janssen HLA, de Man RA. Future prospectives
for the management of chronic hepatitis B. World J
Gastroenterol 2007; 13(18): 2554-2567
http://www.wjgnet.com/1007-9327/13/2554.asp
INTRODUCTION
Treatment of chronic hepatitis B remains an important
clinical objective. Estimates are that 2 billion people have
been infected worldwide and chronic hepatitis B currently
affects about 400 million people, particularly in developing
countries [1] . Chronic hepatitis B is responsible 500 000
to 1.2 million deaths annually from liver cirrhosis and
hepatocellular carcinoma (HCC) [2] . It is one of the most
common infectious diseases and among the world’s leading
causes of death. There are two strategies to decrease these
numbers, prevention of new infections and treatment
of those already chronically infected. Treatment options
consist of immunomodulatory and viral suppressant
drugs. In this review the current standard of care and the
future developments in the field of chronic hepatitis B are
discussed.
WHAT IS THE OPTIONAL TREATMENT
Naïve patients
The ideal treatment for hepatitis B is an effective cheap
treatment, resulting in HBsAg loss and formation of
anti-HBs, with finite treatment duration and little side
effects. Currently none of the HBV treatments fulfill
these conditions. With interferon based therapy HBsAg
loss occurs in 3%-10% of the patients within one year of
start of therapy and increases in sustained responders to
11%-32% [3-9] . HBsAg loss is rare (< 2% after one year of
treatment) in patients treated with nucleos(t)ide analogues,
which is about the rate observed in the natural history
of the disease [10-16] . However, in a small cohort treated
with tenofovir, HBsAg loss was observed in 14% of 35