There are two new nucleoside analogues available for the management of chronic hepatitis B, adefovir and entecavir, and several more in development. In addition, pegylated interferon has become available. Large-scale population studies have re-emphasized the significance of viral load in predicting a poor outcome over the longer term. These new developments have prompted a reassessment of the indications and objectives of therapy for chronic hepatitis B.
Hepatitis B virus deoxyribonucleic acid, rather than alanine aminotransferase should be the prime indication for therapy. Hepatitis B e antigen seroconversion can be achieved in 30–40% of treated patients whatever agent is used. However, it takes longer for nucleoside analogues to achieve the same seroconversion rates as interferon. In anti-HBe-positive disease long-term therapy is required for most patients because the relapse rate after withdrawal of therapy is very high, irrespective of the agent used.
Viral resistance limits the use of lamivudine, and to a lesser extent adefovir. Resistance to entecavir has so far only been described in pre-existing lamivudine resistance. Although therapy with combinations of nucleoside analogues has not been investigated to any extent, this is the only way to reduce the emergence or resistance, and studies are urgently needed.