title: Long-term outcomes of two rescue therapies in lamivudine-refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir.
abstract: OBJECTIVE
  Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option for patients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mg entecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomes of these two rescue therapies.
  
  
  METHODS
  Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). We determined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower limitation of detection, < 140 copies/mL), biochemical response (alanine aminotransferase < 40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough.
  
  
  RESULTS
  Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56 months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P=0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%, respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough and resistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P=0.001).
  
  
  CONCLUSIONS
  Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppression and resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Mediciner, Seoul, Korea.
authors.forename: EunYoung
authors.initials: E
authors.lastname: Ze
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Mediciner, Seoul, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Baek
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Mediciner, Seoul, Korea.
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Mediciner, Seoul, Korea.
authors.forename: Han Wook
authors.initials: HW
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Mediciner, Seoul, Korea.
authors.forename: Dae Geon
authors.initials: DG
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Mediciner, Seoul, Korea.
authors.forename: Hwan Jun
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Mediciner, Seoul, Korea.
authors.forename: Jae Cheol
authors.initials: JC
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Mediciner, Seoul, Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Mediciner, Seoul, Korea.
authors.forename: HyunWoong
authors.initials: H
authors.lastname: Lee
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000410:Alanine Transaminase; D000225:Adenine
keywords: Adefovir; Chronic hepatitis B; Entecavir; Lamivudine; Resistance