title: Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil therapy versus entecavir monotherapy for the treatment-naive patients with chronic hepatitis B: a meta-analysis.
abstract: BACKGROUND
  Currently, there is no consensus on the efficacy and resistance of de novo combination therapy versus monotherapy for treatment naive patients of chronic hepatitis B (CHB).
  
  
  OBJECTIVE
  The aim of this study was to evaluate the effectiveness and resistance of de novo combination of lamivudine (LAM) and adefovir dipivoxil (ADV) compared with entecavir (ETV) monotherapy for nucleos(t)ide-naive patients with CHB.
  
  
  METHODS
  Publications on the effectiveness and resistance of LAM plus ADV versus ETV monotherapy for nucleos(t)ide-naive patients with CHB were identified by a search of PubMed, Embase, the Cochrane Library, Web of science, OVID, and CBM (Chinese Biological Medical Literature) until May 1, 2013. Biochemical response, hepatitis B e antigen seroconversion, and viroligic response were extracted and combined to obtain an integrated result. Viral resistance and safety were reviewed.
  
  
  RESULTS
  Five eligible studies (328 patients in total) were included in the analysis. LAM plus ADV combination therapy produced more rapid HBV DNA reduction rate at 12 weeks than that of ETV monotherapy. At 48 weeks, the combination group had superior viroligic response rates compared with ETV group (90.0% vs. 78.9%, P=0.01). The difference in the ALT normalization and HBeAg seroconversion rates was not found. At week 96, LAM + ADV was more effective than ETV in ALT normalization [RR = 1. 11, 95% CI (1.02, 1.21), P =0.01] and HBeAg seroconversion [RR = 2.00, 95% CI (1.26, 3.18, P=0.003)], and no significant difference was found in the virologic response (P =0.23). No viral resistance occurred in combination therapy and six patients in ETV group were experienced with viral breakthrough. Both groups were well tolerated.
  
  
  CONCLUSIONS
  The de novo LAM plus ADV combination therapy for treatment-naïve patients with CHB was greater than ETV monotherapy in both biochemical response and HBeAg seroconversion rate up to 96 weeks. The rate of emergence of viral resistance in the combination group was less than that in the ETV monotherapy.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.forename: Huaidong
authors.initials: H
authors.lastname: Hu
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. hp_cq@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination / Q000379:methods; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008111:Liver Function Tests; D063065:Organophosphonates / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D006514:Hepatitis B Surface Antigens; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000225:Adenine; C106812:adefovir dipivoxil