title: Lamivudine plus adefovir vs. entecavir in HBeAg-positive hepatitis B with sequential treatment failure of lamivudine and adefovir.
abstract: OBJECTIVE
  Few studies have adequately examined the efficacy of lamivudine plus adefovir (LAM+ADV) combination therapy vs. entecavir (ETV) monotherapy in HBeAg-positive hepatitis B patients who fail to respond to sequential treatment with LAM and ADV. We compared directly the efficacy of LAM+ADV vs. ETV in such patients and assessed prognostic factors associated with a virologic response at month 12.
  
  
  METHODS
  In total, 72 HBeAg-positive patients who showed resistance (n = 33) or a suboptimal virologic response (n = 39) to ADV monotherapy with resistance to LAM therapy underwent rescue therapy (31 LAM+ADV and 41 ETV). All patients were followed for at least 12 months.
  
  
  RESULTS
  Following 12 months of treatment, in the LAM+ADV and ETV groups, a virologic response was observed in 7/31 (22.6%) and 8/41 (19.5%; P = 0.777) patients; ALT normalization occurred in 11/13 (84.6%) and 16/18 (88.9%; P = 0.566); HBeAg seroconversion in 1/31 (2.3%) and 4/41 (9.8%; P = 0.341) and a virologic breakthrough in 3/31 (9.0%) and 5/41 (12.1%; P = 0.452) respectively. Independent prognostic factors associated with a virologic response were the baseline HBV-DNA level (OR = 0.37; 95% CI 0.17-0.80; P = 0.011) and the duration of prior ADV monotherapy (OR = 0.89; 95% CI 0.83-0.95; P = 0.044).
  
  
  CONCLUSIONS
  Neither LAM+ADV nor ETV was adequately effective in patients with sequential LAM and ADV treatment failure. Thus, when chronic hepatitis B patients show resistance or suboptimal response to ADV monotherapy, early modification of treatment should be considered.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Chang Young
authors.initials: CY
authors.lastname: Son
authors.forename: Han Jak
authors.initials: HJ
authors.lastname: Ryu
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Myoung Ha
authors.initials: MH
authors.lastname: Lee
authors.forename: Kwang Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006509:Hepatitis B / Q000188:drug therapy*; D006513:Hepatitis B e Antigens / Q000032:analysis / Q000378:metabolism*; 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*; D011379:Prognosis; D012189:Retrospective Studies; D017211:Treatment Failure
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