Background Hepatitis A is an indolent disease with a varying clinical spectrum and consequences. Little is known about the immune response to hepatitis A virus (HAV) vaccination, in children auto-inflammatory disorders including SoJIA.
Objectives To assess the sero-protective efficacy and safety of immunization against hepatitis A in patients with auto-inflammatory disorders on treatment, not previously exposed to HAV, and compare this to healthy controls.
Methods Matched case control study including patients with FMF, HIDS, FCAS and SoJIA and controls. All subjects received two doses of the inactivated anti-HAV vaccine at 0 and 6 months. Seroconversion and seroportection rates and anti-HAV IgG antibodies were assessed at enrollment, one month after the first dose and at one and 12 months after the last dose. Exclusion criteria were infection or disease flare concomitant or up to four weeks prior to immunization, recent steroid use (dose>0.5mg/kg/day), known liver disease or immunodeficiency, and serum testing positive for HAV infection. Clinical and demographic data as well as medications used were collected for each patient. Onset of typical disease symptoms within two weeks from immunization was considered as a flare.
Results Twenty-eight patients with a mean age of 5.3 years completed the study; 13 (46%) had SoJIA, 13 (46%) had FMF, one had HIDS and one had FCAS. Thirteen (46%) patients received colchicine, 12 (42%) received methotrexate and 10 (35.7%) received steroids while 7 (25%) were on biologics. The control group consisted of 76 healthy individuals (mean age 4.75 years). At four weeks after primary vaccination, 75% of patients and 77.6% (p=0.4) of the controls attained seroprotection. Ninety-two percent and 100% of the patients while 96.1% and 96.1% (P=0.3) of the controls maintained their antibody status four weeks and 52 weeks after the second dose respectively. Seroconversion rates were 90.8%,98.7% and 98% for the patient group and 92.8%,100%, 100% for the controls at 4 weeks after the first dose, and four and 52 weeks after the second dose.
Mean IgG concentration at 4 weeks was 52.7mIU/ml in the patient and 96.2mIU/ml in the control group (t-test, p=0.003) while it reached 131mIU/ml and 218mIU/ml after the second dose respectively (p=0.001). At 18 months mean IgG concentration was 164 mIU/ml in the patient group and 245 mIU/ml in the control group (p=0.002). Subgroup analysis showed that only 72% patients on DMARDS (MTX=/-biologics) achieved seroprotection after the initial vaccine dose, compared to 92.4% of patients on colchicine, however numbers were small to reach statistical significance.Patients with FMF mounted a better immune response compared to SoJIA patients at all time points [74.5IU/ml vs 36.5IU/ml (p=0.046), 172IU/ml vs 99IU/ml (p=0.015), 210IU/ml vs 129 IU/ml (p=0.015) Kolmogorov-Smirnof test]. Three patients developed a flare (1 HIDS and 2 FMF). Vaccines were well tolerated in the other patients. Mild adverse events were noticed in 6/28 (21.4%) patients and 15/76 (19.7%) controls.
Conclusions Two doses of HAV vaccine are safe and effective in the majority of children with autoinflammatory disorders. Systemic illness should not preclude from completion of the vaccination schedule in cases where immunization against Hepatitis A is mandatory. However, based on our small cohort, there seems to be a significant possibility of flare.
Disclosure of Interest None declared