title: Tenofovir-based rescue therapy for chronic hepatitis B patients who had failed treatment with lamivudine, adefovir, and entecavir.
abstract: OBJECTIVE
  In the past decade, many chronic hepatitis B (CHB) patients have undergone sequential treatment with lamivudine (LAM), adefovir (ADV), and entecavir (ETV) to manage antiviral resistance or insufficient suppression of HBV-DNA. Very limited data are available on the efficacy of tenofovir (TDF) rescue regimens in patients with multidrug resistance (MDR).
  
  
  METHODS
  We investigated the antiviral efficacy of TDF/LAM combination therapy versus TDF/ETV combination therapy in 52 patients who failed three previous antiviral therapies.
  
  
  RESULTS
  The study subjects were treated with TDF/LAM combination therapy (n = 25) or TDF/ETV combination therapy (n = 27) for more than six months. Virologic response (VR) occurred in 39 (75%) patients (19 patients belonged to the TDF/LAM group and 20 patients belonged to the TDF/ETV group). The VR rates were not different between the TDF/LAM and TDF/ETV groups (56.0% vs 51.9% at month 12, and 72.0% vs 78.8% at month 18; log rank P = 0.515). In addition, treatment efficacy of TDF/LAM combination or TDF/ETV combination was not statistically different according to types of MDR. In multivariate analysis, absolute HBV-DNA level at the start of TDF rescue treatment (P < 0.001; OR, 0.452; 95% CI, 0.306-0.666) was only significantly associated with VR.
  
  
  CONCLUSIONS
  TDF/ETV combination therapy was not associated with higher rate of VR compared with TDF/LAM combination therapy in MDR CHB patients. These results raise the suspicion about the superiority of the combination therapy over TDF monotherapy. The lower HBV-DNA levels at the start of TDF-based rescue therapy were associated with higher VR.
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Byung Gyu
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Ju Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Shi Jung
authors.initials: SJ
authors.lastname: Sung
authors.affiliation: Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Bo Ryung
authors.initials: BR
authors.lastname: Park
authors.affiliation: Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Chang Jae
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Byung Uk
authors.initials: BU
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: In Du
authors.initials: ID
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Sung-Jo
authors.initials: SJ
authors.lastname: Bang
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.|Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Neung Hwa
authors.initials: NH
authors.lastname: Park
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D063065:Organophosphonates; D000068698:Tenofovir / Q000008:administration & dosage*; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine
keywords: chronic hepatitis B; multidrug resistance; tenofovir