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Long-Term Efficacy of Adefovir for HBeAg-Negative Chronic HBV Infection

Adefovir is effective for long-term treatment of patients with HBeAg-negative infections, although resistance occurs in 20% by 5 years.

Oral nucleoside or nucleotide analogues are the most common drugs prescribed for patients with chronic hepatitis B virus (HBV) infections. However, long-term use of these agents can lead to drug-resistant mutations, which can affect efficacy. This effect is especially evident among hepatitis B e antigen (HBeAg)-negative patients, who require long-term suppressive therapy. In this 5-year international study, researchers evaluated long-term adefovir therapy in HBeAg-negative patients. The study endpoints were percentage of patients with virologic suppression (HBV DNA levels <1000 copies/mL), histologic improvement, and development of resistance.

For the first 48 weeks of double-blind treatment, 185 patients were randomized to either daily adefovir (10 mg) or placebo. Starting at week 49, initial-adefovir patients were rerandomized to continued adefovir or to placebo, and initial-placebo patients were switched to adefovir (10 mg), for an additional 48 weeks. At week 97, 125 patients were enrolled in a 144-week open-label adefovir continuation study (total duration, 240 weeks).

At the end of the continuation study, 67% of patients had virologic suppression; 58% had HBV DNA levels <169 copies/mL. Eighty-three percent of patients had necroinflammatory scores that had improved from baseline; 73% exhibited improvements in fibrosis. The cumulative probability of developing any drug-resistance mutation during treatment was 29%; however, the cumulative probability of developing virologic resistance was only 20%. Long-term safety was excellent: Only 3% of patients showed increased creatinine levels, and all increases were clinically insignificant.

Comment: These researchers demonstrated that adefovir is effective for long-term treatment of patients with HBeAg-negative chronic HBV infections. Virologic suppression and histologic improvement were noted during the 5-year treatment period. Although the overall cumulative development of drug resistance was low, the rate did increase with time. Long-term follow-up data is needed for other currently available oral nucleoside and nucleotide analogues to determine their efficacy and resistance profiles.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology April 6, 2007

Citation(s):

Hadziyannis SJ et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology 2006 Dec; 131:1743-51.

• Medline abstract (Free)

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