What question did this study set out to answer?

This research aims to evaluate the efficacy of adefovir dipivoxil in patients with HBeAg-positive chronic hepatitis B.

February 27, 2003Open Access

Adefovir Dipivoxil for the Treatment of Hepatitis B e Antigen–Positive Chronic Hepatitis B

Key Points

This research aims to evaluate the efficacy of adefovir dipivoxil in patients with HBeAg-positive chronic hepatitis B.
Randomly assigned 515 patients to receive 10 mg or 30 mg of adefovir dipivoxil or placebo daily for 48 weeks.
Primary endpoint was histologic improvement in the 10-mg group versus placebo group.
Adverse events and safety profiles were also assessed.
Histologic improvement was observed in 53% of the 10-mg group and 59% of the 30-mg group compared to 25% in placebo (P<0.001).
Significant reductions in serum HBV DNA levels by medians of 3.52 and 4.76 log copies per milliliter in the 10-mg and 30-mg groups respectively (P<0.001).
HBeAg seroconversion rates were 12% in the 10-mg and 14% in the 30-mg group compared to 6% in placebo, with P-values of 0.049 and 0.01, respectively.

Abstract

BACKGROUND: In preclinical and phase 2 studies, adefovir dipivoxil demonstrated potent activity against hepatitis B virus (HBV), including lamivudine-resistant strains. METHODS: We randomly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg) to receive 10 mg of adefovir dipivoxil (172 patients), 30 mg of adefovir dipivoxil (173), or placebo (170) daily for 48 weeks. The primary end point was histologic improvement in the 10-mg group as compared with the placebo group. RESULTS: After 48 weeks of treatment, significantly more patients who received 10 mg or 30 mg of adefovir dipivoxil per day than who received placebo had histologic improvement (53 percent P<0.001, 59 percent P<0.001, and 25 percent, respectively), a reduction in serum HBV DNA levels (by a median of 3.52 P<0.001, 4.76 P<0.001, and 0.55 log copies per milliliter, respectively), undetectable levels (fewer than 400 copies per milliliter) of serum HBV DNA (21 percent P<0.001, 39 percent P<0.001, and 0 percent, respectively), normalization of alanine aminotransferase levels (48 percent P<0.001, 55 percent P<0.001, and 16 percent, respectively), and HBeAg seroconversion (12 percent P=0.049, 14 percent P=0.01, and 6 percent, respectively). No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene. The safety profile of the 10-mg dose of adefovir dipivoxil was similar to that of placebo; however, there was a higher frequency of adverse events and renal laboratory abnormalities in the group given 30 mg of adefovir dipivoxil per day. CONCLUSIONS: In patients with HBeAg-positive chronic hepatitis B, 48 weeks of 10 mg or 30 mg of adefovir dipivoxil per day resulted in histologic liver improvement, reduced serum HBV DNA and alanine aminotransferase levels, and increased the rates of HBeAg seroconversion. The 10-mg dose has a favorable risk-benefit profile for long-term treatment. No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene.

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