New paradigms for the treatment of chronic hepatitis B
Version of Record online: 10 JUL 2008
© 2008 The Authors. Journal compilation © 2008 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 23, Issue 8pt1, pages 1182–1192, August 2008
How to Cite
Fung, J., Lai, C.-L. and Yuen, M.-F. (2008), New paradigms for the treatment of chronic hepatitis B. Journal of Gastroenterology and Hepatology, 23: 1182–1192. doi: 10.1111/j.1440-1746.2008.05400.x
- Issue online: 31 JUL 2008
- Version of Record online: 10 JUL 2008
- Accepted for publication 31 January 2008.
- drug resistance;
- hepatitis B treatment;
The main goals of chronic hepatitis B treatment should be the long-term suppression of viral replication to minimize disease progression and the risk for the development of hepatocellular carcinoma. Treatment end-points, depending on surrogate markers alone, in particular hepatitis B e-antigen seroconversion, may not be ideal for patients who acquire the disease early in life.
Currently-available drugs include interferons and oral nucleoside/nucleotide analogs. Although interferon therapy provides a finite treatment period, a significant proportion of patients may not respond, and long-term outcome is inconclusive. Long-term efficacy has been demonstrated for both lamivudine and adefovir. However, prolonged nucleoside/nucleotide analog therapy is associated with the emergence of drug-resistant mutations. Therefore, nucleoside/nucleotide analogs with a high genetic barrier and potent antiviral activity, such as entecavir, should be used to reduce the chance of developing drug-resistant mutations. Drugs with a low genetic barrier, including lamivudine and telbivudine, should be used in conjunction with early testing for antiviral response. This can predict favorable outcomes in the long term. The early detection of drug-resistant mutations should prompt clinicians to either add or switch to another agent with a different drug-resistance profile. There are currently no treatment models in the use of combination or sequential therapy in treatment-naïve patients.
To date, long-term treatment appears to be the most effective option. Despite recent advances made with better understanding on the natural history of chronic hepatitis B infection and with newer antiviral drugs available, challenges remain with respect to treatment criteria, treatment end-points, and duration of treatment.