title: Five years of treatment with adefovir dipivoxil in Chinese patients with HBeAg-positive chronic hepatitis B.
abstract: BACKGROUND
  Adefovir dipivoxil (ADV) is a nucleotide analogue with proven efficacy in chronic hepatitis B (CHB).
  
  
  OBJECTIVE
  This study investigated long-term ADV treatment in HBeAg-positive patients.
  
  
  METHODS
  A total of 480 Chinese subjects with HBeAg-positive CHB who participated in a 1-year, double-blind, placebo-controlled study of ADV 10 mg daily were offered open-label continuation for a further 208 weeks.
  
  
  RESULTS
  A total of 390 subjects completed 5 years of treatment. Baseline median hepatitis B virus (HBV) DNA was 8.8 log(10)  copies/ml and alanine aminotransferase (ALT) 2.6 × upper limit of normal. Treatment with ADV resulted in sustained suppression of median HBV DNA by 4.8, 5.0, 5.1, 5.4 and 5.5 log(10)  copies/ml after 1, 2, 3, 4 and 5 years respectively. Continuous treatment with ADV led to a progressive increase in the proportion of subjects achieving undetectable HBV DNA, from 28% after 1 year to 58% after 5 years. HBeAg seroconversion rates increased cumulatively from 11% after 1 year to 29% after 5 years. HBsAg seroconversion was achieved by 1.0% of patients. ADV resulted in ALT normalization that was maintained throughout this study in 75-79% of subjects. Virological breakthrough associated with ADV resistant mutations (rtN236T and rtA181V) occurred in 14.6% of subjects. ADV was well tolerated.
  
  
  CONCLUSIONS
  Five years of ADV treatment in Chinese subjects with HBeAg-positive CHB resulted in increasing virological and serological responses and sustained biochemical responses over time. Virological resistance was identified in 14.6% of patients. Urgent switch or add-on therapy with a nucleoside analogue is necessary if ADV resistant mutations are detected, particularly rtN236T. Treatment was well tolerated.
authors.affiliation: RenJi Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Minde
authors.forename: Mao
authors.initials: M
authors.lastname: Yimin
authors.forename: Yao
authors.initials: Y
authors.lastname: Guangbi
authors.forename: Hou
authors.initials: H
authors.lastname: JinLin
authors.forename: Wang
authors.initials: W
authors.lastname: Hao
authors.forename: Ren
authors.initials: R
authors.lastname: Hong
authors.forename: Wang
authors.initials: W
authors.lastname: Yuming
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xiaqiu
authors.forename: Xu
authors.initials: X
authors.lastname: Daozhen
authors.forename: Chen
authors.initials: C
authors.lastname: Yagang
authors.forename: Niu
authors.initials: N
authors.lastname: Junqi
authors.forename: Chen
authors.initials: C
authors.lastname: Youming
authors.forename: Wang
authors.initials: W
authors.lastname: Yaozong
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dixon
authors.forename: Keith
authors.initials: K
authors.lastname: Barker
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects; D063065:Organophosphonates / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000225:Adenine; C106812:adefovir dipivoxil