title: Entecavir plus adefovir combination treatment for chronic hepatitis B patients after failure of nucleoside/nucleotide analogues.
abstract: BACKGROUND
  The combination of entecavir, a nucleoside analogue, and adefovir, a nucleotide analogue, would be a promising salvage treatment for chronic hepatitis B (CHB) patients who fail nucleoside/nucleotide analogue (NA) regimens.
  
  
  METHODS
  A total of 89 CHB patients who had failed NA regimens and were treated with entecavir plus adefovir combination for at least 12 months were included.
  
  
  RESULTS
  Mean baseline HBV DNA of patients was 6.16 ±1.44 log(10) IU/ml. Patients were classed by the number of previously failed NAs; 1 NA (lamivudine; n=15; Group 1), 2 NAs (lamivudine and either adefovir or entecavir; n=39; Group 2) and 3 NAs (lamivudine, adefovir and entecavir; n=35; Group 3). After 12 months of treatment, the mean reduction in HBV DNA was greater in Group 1 than in Group 2 or 3 (-5.81 ±1.71, -3.20 ±1.36 and -2.93 ±1.56 log(10) IU/ml, respectively; P<0.01). The rates of virological response (HBV DNA<2,000 IU/ml) were 100%, 79.5% and 34.3% (P<0.01), and the rates of complete virological response (HBV DNA<60 IU/ml) were 53.3%, 25.6% and 14.3% in Group 1, 2 and 3, respectively (P<0.01) at 12 months. Higher baseline HBV DNA (odds ratio =0.59; P=0.02) and increasing number of previously failed NAs (P<0.01) were independently associated with a lower rate of complete virological response at 12 months.
  
  
  CONCLUSIONS
  Entecavir plus adefovir combination treatment was effective in achieving virological response in CHB patients after failure of NAs. However, its effect progressively decreased as the number of previously failed NAs increased.
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. limys@amc.seoul.kr
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Lim
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Lee
authors.forename: Nae-Yun
authors.initials: NY
authors.lastname: Heo
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Shim
authors.forename: Han Chu
authors.initials: HC
authors.lastname: Lee
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Suh
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage* / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D004338:Drug Combinations; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine