Treatment with adefovir dipivoxil for 48 weeks resulted in improvements in patients with Hepatitis B e antigen-negative chronic Hepatitis B.
Treatment showed histologic, virologic, and biochemical improvements.
Dr Stephanos Hadziyannis and colleagues evaluated the effect of continued therapy as compared with cessation of therapy.
| Hepatitis B DNA levels were less than 1000 copies per ml in 79% of patients at week 144|
|New England Journal of Medicine|
The researchers assigned 185 Hepatitis B e antigen-negative patients with chronic Hepatitis B to receive 10 mg of adefovir dipivoxil or placebo.
The treatment was given once daily for 48 weeks at a ratio of 2:1.
After week 48, the team randomly assigned patients receiving adefovir dipivoxil either to receive an additional 48 weeks of the drug or to switch to placebo.
The researchers switched patients originally assigned to placebo to adefovir dipivoxil.
Patients treated with adefovir dipivoxil during weeks 49 through 96 were subsequently offered continued therapy by the researchers.
The primary end points were changes in Hepatitis B virus DNA and alanine aminotransferase levels.
The researchers found that treatment with adefovir dipivoxil resulted in a median decrease in serum Hepatitis B DNA of 3.5 log copies per millilitre at 96 weeks.
The team compared this to 3.6 log copies per ml at 144 weeks.
The researchers observed that Hepatitis B DNA levels were less than 1000 copies per ml in 71% of patients at week 96 and 79% at week 144.
In the majority of patients who were switched from adefovir dipivoxil to placebo, the benefit of treatment was lost.
The team noted that the median change in Hepatitis B DNA levels from baseline, were -1 log copies per ml and only 8% had below 1000 copies per ml at week 96.
The researchers observed that side effects during weeks 49 through 144 were similar to those during the initial 48 weeks.
In addition, resistance mutations rtN236T and rtA181V were identified in 6% of patients after 144 weeks.
Dr Hadziyannis' team concludes, “In patients with Hepatitis B e antigen-negative chronic Hepatitis B, the benefits achieved from 48 weeks of adefovir dipivoxil were lost when treatment was discontinued.”
“In patients treated for 144 weeks, benefits were maintained, with infrequent emergence of viral resistance.”