title: Tenofovir has inferior efficacy in adefovir-experienced chronic hepatitis B patients compared to nucleos(t)ide-naïve patients.
abstract: OBJECTIVE
  A recent study reported that entecavir had inferior efficacy in nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients compared to NA-naïve patients. We sought to compare the efficacy of tenofovir disoproxil fumarate (TDF) in NA-experienced and NA-naïve CHB patients.
  
  
  METHODS
  We retrospectively enrolled 252 consecutive patients who had a serum hepatitis B virus (HBV) DNA level greater than 2,000 IU/mL at the initiation of TDF treatment and who received TDF for at least 6 months. Complete virologic suppression (CVS) was defined as undetectable serum HBV DNA. We generated a multivariate Cox proportional-hazard model to examine predictive factors that were independently associated with time to CVS.
  
  
  RESULTS
  The mean age of patients was 48.2 years, and the cohort included 181 NA-naïve patients and 71 NA-experienced patients. The median duration of TDF treatment was 14.4 (interquartile range, 9.5-17.8) months. A total of 167 (92.3%) of 181 NA-naïve patients achieved CVS, and 60 (84.5%) of 71 NA-exposed patients achieved CVS. Forty-nine (89.1%) of 55 patients who previously took an NA aside from adefovir and 11 (68.8%) of 16 adefovir-experienced patients achieved CVS. In multivariable analysis, previous adefovir exposure significantly influenced time to CVS (hazard ratio, 0.37; 95% confidence interval, 0.19-0.72;P=0.003), after adjusting for HBeAg positivity, baseline HBV DNA level and cirrhosis.
  
  
  CONCLUSIONS
  Tenofovir had inferior efficacy in adefovir-experienced CHB patients compared to NA-naïve patients. The response of patients with previous adefovir exposure to TDF monotherapy should be monitored closely.
authors.affiliation: Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Korea.
authors.forename: Goh Eun
authors.initials: GE
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Gastroenterology and Hepatology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Jeong-Ju
authors.initials: JJ
authors.lastname: Yoo
authors.affiliation: Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea.
authors.forename: Minjong
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, CHA Gangnam Medical Center, CHA University, Seoul, Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Dong Hyeon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Ewha Womans University School of Medicine Liver Center, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Hwi Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Su Jong
authors.initials: SJ
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: INSERM Unité 1052, Cancer Research Center of Lyon, Hospices Civils de Lyon, Lyon University, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009711:Nucleotides / Q000737:chemistry / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000068698:Tenofovir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D009711:Nucleotides; D063065:Organophosphonates; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine
keywords: Adefovir; Hepatitis B; Tenofovir