Marcellin P et al. (2004) Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 351: 1206–1217

Responding to the high relapse rates associated with current therapies, Marcellin et al. have compared the efficacy and safety of peginterferon alfa-2a monotherapy, peginterferon alfa-2a plus lamivudine, and lamivudine monotherapy in the treatment of HBeAg-negative chronic hepatitis B.

This international, multicenter study included 537 patients who were randomized to peginterferon alfa-2a once weekly plus placebo once daily (n = 177), peginterferon alfa-2a once weekly plus 100 mg of lamivudine once daily (n = 179) or 100 mg lamivudine once daily (n = 181) for 48 weeks. There was a follow-up period of 24 weeks after the end of treatment.

At the end of follow-up, normalization of alanine aminotransferase levels or suppression of serum HBV DNA levels below 20,000 copies per ml had been sustained in a significantly higher percentage of patients on peginterferon alfa-2a monotherapy (59% and 43%, respectively) or combination therapy (60% and 44%, respectively) than in those on lamivudine monotherapy (44% and 29%, respectively). Sustained suppression of HBV DNA to < 400 copies per ml was also significantly more common in either of the peginterferon alfa-2a groups than in the lamivudine monotherapy group. Loss of HBsAg was noted in a total of 12 patients, all of whom were from the peginterferon alfa-2a groups.

The authors conclude that peginterferon alfa-2a showed significantly improved efficacy over lamivudine and that no additional benefit was seen on addition of lamivudine. This supports the use of peginterferon alfa-2a as a first-line therapy for HBeAg-negative chronic hepatitis B.