title: Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B.
abstract: Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES). At enrollment, the 65 LTSES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log(10) copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 x upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log(10) copies/mL and -50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow-up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A181V or N236T developed in 13 LTSES patients; the first observation was at study week 195. There were no serious adverse events related to ADV.
  
  
  CONCLUSIONS
  Treatment with ADV beyond 48 weeks was well tolerated and produced long-term virological, biochemical, serological, and histological improvement.
authors.affiliation: Hopital Beaujon, Paris, France. patrick.marcellin@bjn.aphp.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
authors.forename: Seng G Lee
authors.initials: SG
authors.lastname: Lim
authors.forename: William
authors.initials: W
authors.lastname: Sievert
authors.forename: Myron
authors.initials: M
authors.lastname: Tong
authors.forename: Sarah
authors.initials: S
authors.lastname: Arterburn
authors.forename: Katyna
authors.initials: K
authors.lastname: Borroto-Esoda
authors.forename: David
authors.initials: D
authors.lastname: Frederick
authors.forename: Franck
authors.initials: F
authors.lastname: Rousseau