title: Emergence of entecavir-resistant mutations in nucleos(t)ide-naive Japanese patients infected with hepatitis B virus: virological breakthrough is also dependent on adherence to medication.
abstract: OBJECTIVE
  Currently, five nucleos(t)ide analogues (NUCs) are available for the treatment of chronic hepatitis B in the world. We examined the prevalence of hepatitis B virus (HBV) DNA and alanine aminotransferase normalization in patients receiving entecavir (ETV) and the frequency of ETV-resistant mutations during an approximately 27-month use of ETV in chronic hepatitis B patients in an urban hospital in Japan.
  
  
  METHODS
  A retrospective analysis of 81 NUC-naive chronic hepatitis B patients who received 0.5 mg of ETV daily was performed. HBV DNA was measured and sequence analysis of HBV DNA was performed in virological breakthrough patients.
  
  
  RESULTS
  Hepatitis B e antigen (HBeAg)-positive patients with HBV DNA 5.0-7.0 log IU/mL group and all HBeAg-negative patients achieved serum HBV DNA negativity by 12 months. Four patients experienced virological breakthrough during ETV therapy. Two patients had no genotypic mutations, and medical interviews revealed that they had poor adherence to ETV.
  
  
  CONCLUSIONS
  We found that some of the HBV virological breakthroughs during ETV treatment were related to poor adherence to medication, highlighting that clinicians should pay attention to the emergence of resistant mutants as well as adherence to ETV.
authors.affiliation: Department of Medicine and Clinical Oncology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kamezaki
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Maruyama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007564:Japan; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase