Is hepatitis-B immunization effective during chronic liver fibrosis? Investigation of secretory and cellular immune responses on an experimental model.

OBJECTIVE: Adults with end-stage of chronic liver diseases have lower antibody titers after hepatitis-B vaccination. We have less amount of knowledge about the effect of non-viral cause chronic liver fibrosis on vaccination. In this study, we investigated the effect of non-viral chronic liver fibrosis on hepatitis B vaccine and the effect of tetanous toxoid co-administration at the level of humoral and cellular immune responses in an experimental model. METHODS: Hepatitis B vaccine was administered either alone or in combination with tetanus toxoid in thioacetamide-induced fibrotic BALB/c mice. Fibrosis level was determined by Knodell scoring. Anti-HBsAg, biochemical parameters, inflammatory (IL-1ß, TNF-α), and anti-inflammatory (IL-10) cytokine levels were investigated in serum samples by automated systems and ELISA; respectively. Frequencies of activated lymphocytes were determined in flow cytometer. RESULTS: Antibody titers significantly decreased after immunization of fibrotic mice. However, co-administration of toxoid significantly elevated antibody titer. The percentage of CD19+CD69+ B lymphocytes was found to be lower in vaccinated fibrotic group compared to vaccinated naive group. Simultaneous administration of toxoid significantly increased the frequencies of CD4+ and CD8+ T cells expressing CD69 and CD127. Interestingly, CD19+CD5+CD1high Breg cells were significantly reduced in the group vaccinated with hepatitis B vaccine and toxoid, simultaneously. The reduction in Breg percentage did not expose a significant decrease in the level of IL-10. CONCLUSION: Non-viral chronic liver fibrosis causes a reduction on specific antibody level after vaccination. Reduction on Breg cell frequency may have an effect on elevation of antibody level after co-administration of tetanus toxoid.