title: Long-term outcomes of add-on adefovir dipivoxil therapy to ongoing lamivudine in patients with lamivudine-resistant chronic hepatitis B.
abstract: OBJECTIVE
  Add-on adefovir dipivoxil (ADV) therapy has been a standard rescue treatment for patients with lamivudine (LAM)-resistant chronic hepatitis B, but the overall benefits of long-term add-on ADV therapy are still limited. The aim of this study was to evaluate the long-term efficiency of add-on ADV treatment and to explore predictive factors associated with it.
  
  
  METHODS
  A total of 158 patients with LAM-resistant chronic hepatitis B were included in this retrospective, multicenter, nationwide study in Japan. After confirming LAM resistance, ADV was added to LAM treatment. Three types of events were considered as outcomes: virological response, hepatitis B e antigen (HBeAg) clearance and alanine aminotransferase (ALT) normalization. Virological response was defined as serum hepatitis B virus (HBV) DNA levels of less than 3 log copies/mL. Baseline factors contributing to these outcomes were examined by univariate and multivariate analyses.
  
  
  RESULTS
  The median total duration of ADV treatment was 41 months (range, 6-84). The rate of virological response was 90.8% at 4 years of treatment; HBeAg clearance and ALT normalization were achieved by 34.0% and 82.7%, respectively, at the end of follow up. Each outcome had different predictive factors: baseline HBV DNA and albumin level were predictive factors for virological response, history of interferon therapy and ALT level for HBeAg clearance, and sex and baseline albumin level for ALT normalization.
  
  
  CONCLUSIONS
  Long-term add-on ADV treatment was highly effective in LAM-resistant chronic hepatitis B patients in terms of virological and biochemical responses. Lower HBV replication and lower albumin level at baseline led to better outcomes.
authors.affiliation: Department of Gastroenterology and Hepatology, NHO, Osaka National Hospital, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Toyama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ishida
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shimada
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohta
authors.forename: Takeaki
authors.initials: T
authors.lastname: Satoh
authors.forename: Michio
authors.initials: M
authors.lastname: Kato
authors.forename: Taizo
authors.initials: T
authors.lastname: Hijioka
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Takano
authors.forename: Toshiki
authors.initials: T
authors.lastname: Komeda
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Yagura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mano
authors.forename: Yukio
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Eiji
authors.initials: E
authors.lastname: Mita