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JAC Advance Access originally published online on March 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 761-785
© 2003 The British Society for Antimicrobial Chemotherapy

Review Article

Hepatitis B virus: old, new and future approaches to antiviral treatment

Peter Karayiannis*

Department of Medicine A, Faculty of Medicine, Imperial College of Science, Technology and Medicine, St Mary’s Campus, South Wharf Road, London W2 1NY, UK

Patients chronically infected with hepatitis B virus (HBV) run the risk of developing cirrhosis and hepatocellular carcinoma in later life. Antiviral treatment offers the only means of preventing such an undesirable outcome. To date, interferon-{alpha} (IFN-{alpha}), an immunomodulator, and two synthetic nucleoside analogues, lamivudine and adefovir dipivoxil, are the only licensed antiviral agents for the treatment of chronic HBV infection. However, the standard treatment endpoints of loss of HBeAg with or without seroconversion to anti-HBe, normalization of serum transaminase levels, loss of HBV-DNA and improvement in liver histology following monotherapy with either types of agent are only achievable in ~20–30% of those treated. Long-term treatment with lamivudine is effective in suppressing viral replication, but drug-resistant mutants arise with increased length of treatment. Nevertheless, such mutants appear to be susceptible to adefovir and other nucleoside analogues that are undergoing Phase II/III clinical trials at the moment. Therapeutic vaccination and other molecular approaches such as antisense oligonucleotides, ribozymes, DNA vaccines, dominant-negative proteins and aptamers are possible future antiviral therapies, which will supplement our armamentarium against chronic HBV infection. It seems certain that combination therapies involving two or more nucleoside analogues, immunomodulators or gene therapies will be the future treatment regimens for chronic HBV infection.

Keywords: HBV, antivirals

* Tel: +44-20-7886-6404; Fax: +44-20-7724-9369; E-mail: p.karayiannis{at}ic.ac.uk


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