Adefovir dipivoxil in the treatment of chronic hepatitis B virus infection
- Anna SF Lok, MD
Anna SF Lok, MD
- Professor of Medicine
- University of Michigan Medical School
Adefovir dipivoxil (Hepsera) is a nucleotide analog of adenosine monophosphate, which can inhibit reverse transcriptase and DNA polymerase activity [1,2]. Adefovir has been evaluated as primary monotherapy for patients with chronic hepatitis B and in patients who developed resistance to lamivudine. It was approved by the FDA based upon the results of two phase 3 clinical trials in patients with HBeAg positive and HBeAg negative chronic hepatitis B and a compassionate use protocol for patients with decompensated cirrhosis or recurrent hepatitis B post-transplantation and lamivudine resistance. Several other studies evaluating adefovir in other populations have also been performed.
This topic review will discuss the treatment of chronic hepatitis B with adefovir. A general approach to patients with hepatitis B (including other treatment options) is presented separately. (See "Overview of the management of hepatitis B and case examples".)
HBeAg POSITIVE CHRONIC HEPATITIS B
The efficacy of adefovir in HBeAg positive patients has been demonstrated in at least two large, placebo controlled trials [3,4]. The largest trial included 515 patients with compensated liver disease who were randomly assigned to two doses of adefovir (10 or 30 mg) or placebo . The study was open to treatment naive patients as well as those who had failed interferon. The following benefits were observed compared with placebo in the 10 mg group (the approved dose) after 48 weeks of treatment; all results were statistically significant:
●Histologic improvement, defined as decrease in Knodell histologic inflammatory score by at least two points with no worsening in fibrosis (53 versus 25 percent)
●Improvement in fibrosis based on ranked assessment (41 versus 24 percent)
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- HBeAg POSITIVE CHRONIC HEPATITIS B
- Durability of HBeAg seroconversion
- HBeAg NEGATIVE CHRONIC HEPATITIS B
- Adefovir monotherapy
- HBsAg LOSS
- PATIENTS WITH LAMIVUDINE RESISTANCE
- Liver transplantation and decompensated liver disease
- Compensated liver disease
- HIV coinfection
- DEVELOPMENT OF RESISTANCE
- Effect of lamivudine cotherapy
- Susceptibility of adefovir-resistant HBV to other agents
- SUMMARY AND RECOMMENDATIONS