Source: Urology  |  Posted 5 years ago

By Maria Bishop

BOSTON, MA -- November 3, 2006 -- In a study of patients with hepatitis e antigen (HBeAg)-positive chronic hepatitis B virus (HBV), 91% experienced lasting seroconversion of HBeAg after a median of 5 years of treatment with adefovir dipivoxil (10 mg daily) in a placebo-controlled trial, researchers reported here at the 57[^]th[] Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

Patrick Marcellin, MD, professor, department of hepatology, Institut Nationale de la Sant? et de la Recherche M?dicale (INSERM) Unit 481, H?pital Beaujon, Clichy, France, led an international team of researchers in following HBeAg-positive subjects over the course of 5 years.

The first-year improvements during therapy, he noted, were virological, serological, and biochemical (N Engl J Med 2003; 348:808-16), with no resistance mutations detected. Patients were randomised to receive adefovir 10 mg, adefovir 30 mg, or placebo. Most patients had multiple doses of placebo in year 2 due to an error in drug allocation.

Patients given adefovir 10 mg in year 1 who did not seroconvert in years 1 and 2 (n = 65) were allowed to continue in the long-term safety and efficacy study, with assessments every 3 months for 3 years, explained Dr. Marcellin.

Patients were predominantly male (83%) with a median age of 34; 74% were Asian. Median serum HBV deoxyribonucleic acid (DNA) was 8.45 log[_]10[] copies/mL, and the median alanine aminotransferase (ALT) was 2.0 times the upper limit of normal (ULN).

Upon follow-up through year 5, 38 of the 65 patients had a confirmed rebound in HBV DNA or were never fully suppressed. At 5 years, the median change from baseline in serum HBV DNA and ALT for the 41 patients still on adefovir was -4.05 log[_]10[] copies/mL and -50 U/L, Dr. Marcellin noted.

Probabilities of HBeAg loss and seroconversion at 240 weeks were 60% and 48%, respectively. Four patients (2%) lost hepatitis B s antigen (HBsAg) and seroconverted to anti-HBs.

Adefovir-resistant mutations A181V and/or N236T were detected in 13 of the long-term study patients (20%) beginning at week 195; 12 patients (18%) also had virologic resistance and 5 patients had clinical resistance.

There were no serious adverse events related to adefovir.

Dr. Marcellin concluded that these results showed positive long-term safety and efficacy in a difficult-to-treat population. Liver biopsies of 15 patients taken at baseline were compared again after long-term follow up and demonstrated improvements in necroinflammation and fibrosis in the majority of patients.

[Presentation title: Long-term Efficacy and Safety of Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B (CHB) Patients. Poster 969]