title: Interferon for treatment of breakthrough infection with hepatitis B virus mutants developing during long-term lamivudine therapy.
abstract: BACKGROUND
  We aimed to treat patients with chronic hepatitis B on long-term treatment with lamivudine who developed lamivudine-resistant hepatitis B virus (HBV) mutants along with clinical relapses.
  
  
  METHODS
  Of 217 patients with chronic hepatitis B who had been treated with lamivudine for 1-6 years, 23 (11%) developed lamivudine-resistant hepatitis B virus (HBV) mutants. Seven of them, including 1 whose case was previously reported, received interferon (IFN) daily for 4 weeks and then two or three times a week thereafter to cope with exacerbation of hepatitis. We investigated the efficacy of this IFN therapy in 6 patients, excluding the 1 previously reported.
  
  
  RESULTS
  In 4 patients, HBV DNA decreased to below the detectable limit of the branched DNA assay (<0.7 MEq/ml) accompanied by normalization of transaminase levels. During IFN therapy, 2 patients seroconverted to antibody to hepatitis B e antigen (HBeAg) and showed normalized transaminase levels. Interferon was required in 7 of the 111 (6%) patients with chronic hepatitis B who were positive for HBeAg, but in none of the 106 who were positive for antibody to HBeAg ( P = 0.014).
  
  
  CONCLUSIONS
  The efficacy of IFN in controlling virological breakthroughs and exacerbation of hepatitis by infection with lamivudine-resistant HBV mutants in patients with HBeAg-positive chronic hepatitis B could enhance the versatility of lamivudine, which may have to be given to them indefinitely.
authors.affiliation: Research Institute for Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Takashi
authors.initials: T
authors.lastname: Someya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
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: Yuzo
authors.initials: Y
authors.lastname: Miyakawa
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D012008:Recurrence; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D007372:Interferons