title: Failure of therapeutic vaccination using hepatitis B surface antigen vaccine in the immunotolerant phase of children with chronic hepatitis B infection.
abstract: OBJECTIVE
  The aim of this study was to investigate the efficacy of specific hepatitis B virus (HBV) vaccination as active immunotherapy in treating chronic hepatitis B (CHB) infection during the immune-tolerant phase in children with normal aminotransferase levels and high viral load.
  
  
  METHODS
  Fifty-one immunotolerant patients were randomly and prospectively recruited into two groups. Group 1 included 23 patients that were vaccinated with three standard injections of the GenHevac B vaccine in the deltoid or quadricep muscle, initially, and at 30 days and 60 days, for specific immunization. Group 2 contained 28 patients who did not receive any medication or vaccination and were recruited as the control group. Post-vaccination evaluation was performed at 6 months from the first injection and at the end of the 12th month by serological and virological analyses. A response criterion to therapy was defined as loss of HBV-DNA in serum and hepatitis B early antigen (HBeAg) seroconversion (loss of HBeAg, development of antibody to HBeAg (anti-HBe)).
  
  
  RESULTS
  The mean alanine aminotransferase (ALT) value in group 1 at the beginning of the vaccination was 33.6 +/- 8.1 IU/L; this changed to 31.7 +/- 9.0 IU/L at 6 months after first injection and 29.2 +/- 7.1 IU/L at the end of 12 months (P > 0.05). In this group, mean HBV-DNA load at the starting point of the vaccination was 3,709 +/- 1,126 pg/mL; this value changed to 3,569 +/- 726 pg/mL at the sixth month and 3,295 +/- 832 pg/mL at the 12th month (P > 0.05). In group 2, the mean ALT values at the beginning of therapy, and at the 6th and 12th month were 32 +/- 8 IU/L, 31.8 +/- 8 IU/L, and 29.7 +/- 7 IU/L, respectively (P > 0.05), and the mean viral load of HBV-DNA values were 3,827 +/- 1,375 pg/mL, 3,498 +/- 886 pg/mL, and 3,059 +/- 731 pg/mL, respectively (P > 0.05). The load of HBV DNA of all patients in both groups was greater than 2,000 pg/mL. There was no statistically significant difference in the mean ALT values and mean viral load of HBV DNA (P > 0.05) between group 1 and group 2 at the end of the 6th and 12th months. Except for one each patient in each group, hepatitis B surface antigen (HBsAg) and HBeAg clearance or antibody to HBsAg (anti-HBs) and anti-HBe seroconversion were not observed during the follow-up period (P > 0.05).
  
  
  CONCLUSIONS
  In this study, comparison of vaccinated and unvaccinated groups of immunotolerant children with CHB infection showed no difference in the clearance of HBV DNA and seroconversion of HBeAg to anti-HBe. Different immunization protocols should be considered for future investigations in the immunotolerant phase of children with CHB infection.
authors.affiliation: Department of Pediatric Gastroenterology, Dicle University Medical Faculty, Diyarbakir, Turkey. bdikici@dicle.edu.tr
authors.forename: Bunyamin
authors.initials: B
authors.lastname: Dikici
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bosnak
authors.forename: Hasan
authors.initials: H
authors.lastname: Ucmak
authors.forename: Abdullah
authors.initials: A
authors.lastname: Dagli
authors.forename: Aydin
authors.initials: A
authors.lastname: Ece
authors.forename: Kenan
authors.initials: K
authors.lastname: Haspolat
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D002648:Child; D051263:D-Alanine Transaminase; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000628:therapy*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D017211:Treatment Failure; D014611:Vaccination / Q000379:methods*
chemical_list: D004279:DNA, Viral; C075656:GenHevac B Pasteur; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase; D051263:D-Alanine Transaminase