title: Long-term use of entecavir in nucleoside-naïve Japanese patients with chronic hepatitis B infection.
abstract: OBJECTIVE
  To evaluate the long-term efficacy of entecavir in nucleoside-naïve chronic hepatitis B patients.
  
  
  METHODS
  One hundred and sixty-seven patients treated with entecavir 0.01mg, 0.1mg or 0.5mg for 24-52weeks in Phase II studies entered rollover study ETV-060 and received entecavir 0.5mg daily. Responses were evaluated among patients with available samples.
  
  
  RESULTS
  After 96weeks in ETV-060 (120-148weeks total entecavir treatment time), 88% (127/144) of patients had HBV-DNA <400 copies/ml; 90.1% (128/142) had alanine aminotransferase (ALT) 1x the upper limit of normal (ULN) among those with abnormal baseline ALT; and 26% (32/121) achieved HBe seroconversion among those HBeAg(+) at baseline. A subset of 66 patients received entecavir 0.5mg (approved dose) from Phase II baseline: at week 96 in ETV-060, 83% (48/58) had HBV-DNA <400 copies/ml, 88% (52/59) had ALT 1x ULN, and 20% (10/49) achieved HBe seroconversion. Twenty-one out of 66 patients had paired baseline and on-treatment biopsies: 100% (21/21) and 57% (12/21) demonstrated histologic improvement, and improvement in fibrosis, respectively, over 3years. The 3-year cumulative probability of resistance was 3.3% for all patients and 1.7% for the 0.5mg subset.
  
  
  CONCLUSIONS
  Long-term entecavir for nucleoside-naïve patients resulted in high rates of virological, biochemical, and histological response, with minimal resistance.
authors.affiliation: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.forename: Koichi
authors.initials: K
authors.lastname: Takaguchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Fujioka
authors.forename: Michiko
authors.initials: M
authors.lastname: Shindo
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kobashi
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Chifumi
authors.initials: C
authors.lastname: Sato
authors.forename: Kendo
authors.initials: K
authors.lastname: Kiyosawa
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Tanikawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Masaki
authors.forename: Taku
authors.initials: T
authors.lastname: Seriu
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D044466:Asian People; D001706:Biopsy; D015331:Cohort Studies; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009705:Nucleosides; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D009705:Nucleosides; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase