Semin Liver Dis 2006; 26: 116-129 DOI: 10.1055/s-2006-939750
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Hepatitis B e Antigen-Positive Chronic Hepatitis B: Natural History and Treatment
Jordan J. Feld1, E. Jenny Heathcote2
1 Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 2 University Health Network-Toronto Western Hospital, Toronto, Ontario, Canada

ABSTRACT

The natural history of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is very heterogeneous. Age at acquisition is a major factor in determining the natural history of chronic infection. The vigor of the host immune response to the virus, viral factors (genotype, core promoter mutations, and duration of viral replication) as well as exogenous factors (alcohol, immune suppression) all influence the severity of disease. The goal of antiviral therapy is HBeAg seroconversion, and preferably HB surface Ag seroconversion as this latter end-point is associated with sustained immune control and the halting of disease progression. Although peginterferon is now considered as the first line of therapy for HBeAg-positive chronic hepatitis B, in most cases there are circumstances where nucleos(t)ide analogues are indicated (e.g., decompensated liver disease) for those requiring cancer chemotherapy/other immunosuppressive agents and for those with contraindications to interferon. The major challenge for the clinician using these agents is the emergence of antiviral drug resistance. Long-term immune control of viral replication is key to improving patient outcome.

KEYWORDS

Immunotolerant state - HBeAg seroconversion - pegylated interferon - nucleos(t)ide therapies - drug resistance - risk factors - severe hepatitis B