Objectives: Hepatitis B virus (HBV) reactivation has been described in patients treated with infliximab for inflammatory bowel disease (IBD). This has resulted in a "black box" warning. Although universal vaccination against hepatitis B was implemented in the United States in 1991, up to 10% of vaccine recipients fail to respond with adequate anti-hepatitis B surface antibodies (anti-HBs) levels after a primary series of vaccinations. In addition, anti-HBs levels are expected to decline with time. The objectives of this study were to determine HBV immunity in children with IBD on infliximab therapy and to determine response to a booster dose of the HBV vaccine in patients who were found to be non-immune.
Methods: This was a prospective cross-sectional, single-center study that included 100 pediatric IBD patients on infliximab. Serologic specimens were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and anti-HBs. Patients with an anti-HBs level ≥10 mIU/ml were considered to be immune. One booster dose was given to non-immune patients and a serum sample was collected after 4 weeks to assess the presence of anamnestic response (anti-HBs level ≥10 mIU/ml after booster).
Results: The mean age of the patients was 17.9 (±4.0) years. None of the patients were positive for HBsAg or anti-HBc. In all, 87 patients were vaccinated against HBV and 49/87 (56%) had immunity to HBV as defined by anti-HBs level ≥10 mIU/ml. The mean concentration of anti-HBs levels in immune patients was 295.6 (±350.6) mIU/ml. Older age, lower albumin levels, and the presence of pancolitis were associated with the absence of protective antibodies; however, infliximab dose, frequency, duration, and the concurrent use of immunomodulators were not significantly different between immune and non-immune patients. Thirty-four patients received booster immunization and 26/34 (76%) had an anamnestic response. Interestingly, non-responders were given infliximab with higher frequency (every 5.9 ± 1.2 weeks vs. every 7.1 ± 1.8 weeks, P=0.01). Overall, 75/87 (86%) of previously immunized patients were considered immune against HBV infection.
Conclusions: In pediatric IBD patients seen at a large, urban tertiary care facility in the United States, a significant minority (13%) have not been vaccinated against HBV. Nearly one-half of all patients (and 44% of previously vaccinated patients) did not have protective anti-HBs levels. Moreover, of those previously vaccinated, a significant minority (14%) appear at risk for HBV because protective anti-HBs levels were absent and could not be elicited through booster immunization. Given the high risk for severe HBV infection in this group, efforts should be made to screen for HBV immunity at the time of IBD diagnosis. Booster immunization should be considered in patients without protective antibodies.