title: Efficacy of long-term tenofovir-based rescue therapy in patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs.
abstract: BACKGROUND
  Few studies have investigated the efficacy of long-term tenofovir disoproxil fumarate (TDF)-based rescue therapy in patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs.
  
  
  METHODS
  We retrospectively analyzed 40 Japanese patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs who received TDF-based rescue therapy [TDF monotherapy, TDF plus lamivudine (LAM) combination therapy, or TDF plus entecavir (ETV) combination therapy] followed up for a median of 45 months (range 14-99 months). Viral response, changes in hepatitis B surface antigen levels from the baseline, and viral breakthrough during therapy were analyzed.
  
  
  RESULTS
  The proportion of patients with undetectable serum hepatitis B virus (HBV) DNA levels (less than 2.1 log copies per milliliter) (viral response) during TDF-based rescue therapy was 68, 78, 85, 88, 83, 81, 88, and 100 % at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, and 4 years respectively. There were no differences in the viral response rate between the TDF plus LAM group and the TDF plus ETV group. The mean reduction from the baseline in hepatitis B surface antigen levels in patients with LAM-resistant HBV was greater than the reductions in patients with adefovir dipivoxil (ADV)-resistant or ETV-resistant HBV at 2 and 3 years (P = 0.024, and P = 0.025 respectively). However, two patients with ADV- or ETV-resistant HBV at the baseline developed viral breakthrough during TDF-based rescue therapy.
  
  
  CONCLUSIONS
  Long-term therapy with a TDF-based rescue regimen demonstrated high viral suppression in patients in whom LAM plus ADV combination therapy, ETV plus ADV combination therapy, or ETV monotherapy had failed. However, patients with ADV- or ETV-resistant HBV at the baseline may develop viral breakthrough and resistance, and careful follow-up is advised.
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. fumitakas@toranomon.gr.jp.|Okinaka Memorial Institute for Medical Research, Tokyo, Japan. fumitakas@toranomon.gr.jp.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Fujiyama
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Mineta
authors.affiliation: Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000068698:Tenofovir / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000068698:Tenofovir
keywords: Drug resistance; Entecavir; Hepatitis B virus; Lamivudine; Tenofovir disoproxil fumarate