title: Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of Entecavir (ETV) plus adefovir (ADV) for chronic hepatitis B (CHB) patients after multiple nucleos(t)ide analogue (NAs) failure treatment.
  
  
  METHODS
  Hepatitis B e antigen (HBeAg)-positive patients who had a suboptimal response or developed resistance to two or more previous NAs treatments were included, and all subjects were treated with ETV in combination with ADV for ≥ 24 months. Complete virologic response (CVR) was defined as an undetectability of serum hepatitis B virus (HBV) DNA level during treatment. Safety assessment was based on the increasing of serum creatinine and creatine kinase levels.
  
  
  RESULTS
  A total of 45 eligible patients were included. Twenty-five patients had been treated with lamivudine (LAM) or telbivudine (LdT) and developed genotypic resistance. Resistance to ADV was present in 18 patients and 4 patients had a suboptimal response to ETV. Two patients had a resistance to both LAM and ADV. The cumulative probabilities of CVR at 12 and 24 months of ETV + ADV treatment were 88.9% (40/45) and 97.8% (44/45), respectively. Although one patient failed to achieve CVR, its serum HBV DNA level decreased by 3.3 log copies/mL after 24 months of combination therapy. The cumulative probability of HBeAg seroconversion was 15.6% (7/45) and 26.7% (12/45) at 12 and 24 months of treatment, respectively. History of prior exposure to specific NAs did not make a difference to ETV + ADV treatment outcome. There were no significant adverse events related to ETV + ADV therapy observed in the study subjects.
  
  
  CONCLUSIONS
  ETV + ADV can be used as an effective and safe rescue therapy in patients after multiple NA therapy failures, especially in the areas where tenofovir is not yet available.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Xu
authors.forename: Gai-Li
authors.initials: GL
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Qin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Fa-Qun
authors.initials: FQ
authors.lastname: He
authors.forename: Jin-Ye
authors.initials: JY
authors.lastname: Li
authors.forename: Quan-Rong
authors.initials: QR
authors.lastname: Pan
authors.forename: Jie-Yin
authors.initials: JY
authors.lastname: Deng
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; C413685:entecavir; D006147:Guanine; C053001:adefovir; D003404:Creatinine; D003402:Creatine Kinase; D000225:Adenine