title: Efficacy of entecavir treatment for lamivudine-resistant hepatitis B over 3 years: histological improvement or entecavir resistance?
abstract: OBJECTIVE
  Long-term lamivudine therapy is required for patients with chronic hepatitis B, because hepatitis reappears frequently after it has withdrawn. However, hepatitis B virus (HBV) mutants resistant to lamivudine emerge frequently accompanied by breakthrough hepatitis.
  
  
  METHODS
  Effects of entecavir were evaluated in 19 patients who had developed breakthrough hepatitis during lamivudine therapy for longer than 5 years. This study is a subgroup analysis of a previously reported study. Entecavir, in either 0.5 or 1.0 mg/day doses, was given to 10 and nine patients for 52 weeks, respectively, and then all received 1.0 mg/day entecavir for an additional 68-92 weeks.
  
  
  RESULTS
  There were no differences in biochemical and virological responses in the two groups of patients with respect to the two different initial doses of entecavir. Serum levels of alanine aminotransferase were normalized in 17 (90%) patients, and hepatitis B e antigen (HBeAg) disappeared from the serum in two (14%) of the 14 patients who were HBeAg-positive before. Furthermore, a decrease in histological activity index score greater than 2 points was achieved in nine of the 11 (82%) patients in whom annual liver biopsies were performed during 3 years while they received entecavir. HBV mutants resistant to entecavir emerged in five of the 19 (26%) patients, and hepatitis flare occurred in two of them (40%).
  
  
  CONCLUSIONS
  Entecavir in the long term would be useful for histological improvement of breakthrough hepatitis induced by lamivudine-resistant HBV mutants in patients with chronic hepatitis B. However, the relatively high rate of entecavir resistance is a concern, and other strategies need to be considered when available.
authors.affiliation: Department of Hepatology, Toranomon Hospital, Takatsu-ku, Kawasaki City, Japan. suzunari@interlink.or.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yatsuji
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Miyakawa
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007564:Japan; D019259:Lamivudine / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase