Failure of therapeutic vaccination using hepatitis B surface antigen vaccine in the immunotolerant phase of children with chronic hepatitis B infection

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. 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)). 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 3709 +/- 1126 pg/mL; this value changed to 3569 +/- 726 pg/mL at the sixth month and 3295 +/- 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 3827 +/- 1375 pg/mL, 3498 +/- 886 pg/mL, and 3059 +/- 731 pg/mL, respectively (P > 0.05). The load of HBV DNA of all patients in both groups was greater than 2000 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). 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.