Long-term follow up of Hepatitis B virus-specific immune response in liver transplant patient receiving third-generation hepatitis B vaccine

Abstract

BACKGROUND AND AIM: Vaccination is associated with lower seroconversion rate in immunosuppressed patients. In our previous study, with the use of 3rd generation pre-S containing Hepatitis B virus (HBV) vaccine (Sci-B-Vac™), 50% (10/20) liver transplant patients had hepatitis B surface antigen (HBsAg) seroconversion and 7 with sustained (>6 months) antibody production. We aim to investigate the long-term efficacy of the third-generation recombinant HBV vaccine in immunocompromised liver transplant patients. PATIENTS AND METHODS: All patients recruited for vaccination had undergone HBV-related liver transplantation and had no evidence of HBV recurrence or immunity at more than 12 months (median 20.9 months, range 12.8 – 87.6 months) after transplantation. Among the 20 patients, 2 patients (1 responder and 1 non-responder) had loss follow-up due to immigration. Twelve out of 18 patients with median follow-up 63.6 months (range 63-64 months) from date of vaccination were recruited. Serum HBsAg and anti-HBs levels were monitored. Peripheral blood samples were obtained from each patient. HBV-specific T cell interferon-γ (IFN-γ) ELISPOT was performed. Phenotypes of circulating T- and B-lymphocytes were analysed by FACS. RESULTS: All 12 patients had no evidence of HBV recurrence at last follow-up. Six out of 12 (50%) patients were vaccination responders. Three non-responders were undergoing haemodialysis. Anti-HBs level was detectable (>10 IU/mL) in 3 responders (median 27 IU/mL, range 14-73 IU/mL). IFN-γ secreting T-lymphocyte to HBcAg was higher in responder (mean=5.1 SFC/2x105 PBMC) than in non-responder (mean=1.4 SFC/2x105 PBMC), while response to HBsAg was lower in responder (mean=2.1 SFC/2x105 PBMC) than in non-responder (mean=2.7 SFC/2x105 PBMC). Peripheral blood memory B-lymphocytes in responder was higher (median 0.52, range 0.04 - 0.74 [% out of total nucleated cells] vs median 0.13, range 0.04 - 0.33 [% out of total nucleated cells]) (p=0.026). CONCLUSIONS: Long-term efficacy with the use of 3rd generation recombinant HBV vaccine was demonstrated by the sustained anti-HBs production for >5 years after vaccination. Suggesting active HBV immunization can be achieved in immunocompromised patients with the use of a more immunogenic vaccine. Low T-lymphocytes response might due to the absence of antigenic stimulation in patients without HBV recurrence.