Long-Term Therapy with Adefovir Dipivoxil for HBeAg-Negative Chronic Hepatitis B

In the second phase of a randomized, placebo-controlled trial of adefovir dipivoxil for the treatment of hepatitis B e antigen (HBeAg)–negative chronic hepatitis B, patients who had been treated with adefovir during the initial 48 weeks of the trial were randomly assigned to be switched to placebo or to continue to receive adefovir. Patients who were switched to placebo lost the benefits that had been gained during the initial 48 weeks of treatment, and patients randomly assigned to continue adefovir therapy maintained a response. Resistance mutations developed in 6 percent of the patients treated with adefovir dipivoxil for 144 weeks. Patients who were switched to placebo after 48 weeks lost the benefits that had been gained during initial treatment, and patients randomly assigned to continue adefovir therapy maintained a response. An estimated 400 million people worldwide are chronically infected with hepatitis B virus (HBV). One million die each year from complications of infection, including cirrhosis, hepatocellular carcinoma, or both. 1 Hepatitis B e antigen (HBeAg)–negative chronic hepatitis B represents a late phase in the course of HBV infection. 2 Mutations in the precore promoter regions, core promoter regions, or both, which prevent the formation of HBeAg, are selected during or after HBeAg loss and seroconversion to antibody to HBeAg (anti-HBe). HBeAg-negative chronic hepatitis B infection is characterized by intermittent periods of exacerbation and quiescence. It frequently follows an aggressive disease course, with . . .