title: In vivo immunization by vaccine therapy following virus suppression by lamivudine: a novel approach for treating patients with chronic hepatitis B.
abstract: BACKGROUND
  Both the hepatitis B virus (HBV) and the immune response of the hosts to HBV play important roles in the pathogenesis of chronic hepatitis B (CHB). Lamivudine is a potent antiviral agent with minimal immune modulator capacity. Moreover, lamivudine causes severe side effects like breakthrough of HBV DNA and breakthrough hepatitis in patients with CHB. On the other hand, vaccine therapy, a recently-developed immune therapy, exhibits potent immune modulatory potentials and almost no side effects, but possesses little antiviral capacity in patients with CHB.
  
  
  OBJECTIVE
  The aim of this clinical trial is to evaluate the efficacy of a combination therapy of lamivudine and vaccine in patients with CHB.
  
  
  METHODS
  Seventy-two patients with CHB (hepatitis B e antigen (HBeAg)-positive, 40; antibody to HBeAg (anti-HBe)-positive, 32). All patients received lamivudine at a dose of 100 mg daily for 12 months. Fifteen patients (HBeAg+, 9; anti-HBe+, 6) receiving oral lamivudine were also given a vaccine containing 20 microg of hepatitis B surface antigen, intradermally, once every 2 weeks for 12 times (combination therapy).
  
  
  RESULTS
  Twelve months after the start of therapy, serum HBV DNA became negative in 9 of 9 (100%) HBeAg+ CHB patients receiving combination therapy and in 15 of 31 (48%) HBeAg+ CHB patients receiving lamivudine monotherapy (P < 0.05). The rate of seroconversion from HBeAg to anti-HBe was also significantly higher in patients receiving combination therapy (56% versus lamivudine monotherapy, 16%, P < 0.05). Of the 57 patients receiving lamivudine monotherapy, breakthrough of HBV DNA was found in 10 and breakthrough hepatitis was found in 4; however, these were not seen in any patient receiving combination therapy.
  
  
  CONCLUSIONS
  Combination therapy represents a better therapeutic regimen with few complications in patients with CHB.
authors.affiliation: Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-Cho, Ehime 791 0295, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Horiike
authors.forename: Sk Md
authors.initials: SM
authors.lastname: Fazle Akbar
authors.forename: Kojiro
authors.initials: K
authors.lastname: Michitaka
authors.forename: Kouji
authors.initials: K
authors.lastname: Joukou
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Naohiko
authors.initials: N
authors.lastname: Kojima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiasa
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.forename: Morikazu
authors.initials: M
authors.lastname: Onji
mesh_terms: D000328:Adult; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007114:Immunization; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D017325:Hepatitis B Vaccines; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine