title: Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B.
abstract: BACKGROUND
  Large clinical studies assessing long-term adefovir dipivoxil salvage monotherapy in patients with lamivudine-resistant chronic hepatitis B (CHB) are lacking, particularly in patients positive for hepatitis B e antigen (HBeAg). We assessed the efficacy and resistance profile of adefovir dipivoxil monotherapy for up to 5 years in a large cohort of Korean patients with lamivudine-resistant CHB.
  
  
  METHODS
  A total of 320 patients (81.3% HBeAg-positive; 100% genotype C) with confirmed genotypic lamivudine-resistant CHB were switched to adefovir dipivoxil 10 mg once daily. Liver function tests and HBV DNA were monitored every 3 months. Genotypic resistance to adefovir dipivoxil was performed in patients with detectable HBV DNA.
  
  
  RESULTS
  The overall cumulative virological response rate at 5 years of adefovir dipivoxil therapy was 48.8%. The virological response rate was significantly higher in HBeAg-negative patients (62.0% versus 45.9%; P=0.010). Most cases of virological response (131/134, 97.8%) occurred within the first 36 months of therapy. The 5-year cumulative probability of genotypic resistance and virological breakthrough was 65.6% and 61.8%, respectively. Predictive factors for a virological response included baseline HBeAg seronegativity, HBV DNA< or =8 log(10) copies/ml and achievement of an on-treatment initial virological response.
  
  
  CONCLUSIONS
  Adefovir dipivoxil salvage monotherapy for lamivudine-resistant CHB resulted in a modest cumulative virological response rate at 5 years, which was associated with progressive antiviral resistance. Consequently, adefovir monotherapy is not preferable as a first-line strategy for lamivudine resistance where combination lamivudine plus adefovir dipivoxil therapy is available.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Tin
authors.initials: T
authors.lastname: Nguyen
authors.forename: Sun Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Kim
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007723:Korea; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil