Entecavir: new drug. Chronic hepatitis B: a last resort.

(1) For patients with HBeAg-positive chronic hepatitis B, peginterferon alfa-2a is the standard treatment used to prevent clinical complications and death. Lamivudine and adefovir dipivoxil, both taken orally, are second-line options. They can also be used as first-line treatments in patients with HBeAg-negative chronic hepatitis B if the adverse effects of prolonged peginterferon therapy are likely to pose a major problem. (2) Entecavir, a nucleoside analogue, is now marketed for oral treatment of chronic hepatitis B in adults. (3) Entecavir has not been compared with adefovir in clinical trials. Its evaluation is based mainly on three 48-week trials versus lamivudine. When given at a dose of 0.5 mg/day to patients who had not yet received antiviral treatment, and at a dose of 1 mg/day to patients in whom lamivudine had failed, entecavir was significantly more effective than lamivudine, in terms of effects on liver histology and viral load. The possible clinical implications of these effects are not known. (4) In these trials, similar types and frequencies of adverse effects occurred with entecavir and lamivudine, mainly consisting of headache (about 20% of patients) and other neurological disorders. Hepatitis rebound occurred in less than 10% of patients during or after both treatments but at slightly different times. (5) Entecavir was carcinogenic in experimental animals. No increase in the frequency of cancer has been seen in clinical trial participants thus far, but follow-up is limited. (6) Given the uncertainties concerning the potential adverse effects of entecavir and the fact that it affects viral load in patients in whom lamivudine fails, entecavir should only be used when lamivudine and adefovir have failed.