To the Editor: We read with great interest the new ESPGHAN guidelines for the diagnosis of celiac disease (CD) (1). Regarding the categories at increased CD risk requiring specific antibodies testing, we believe that individuals with (selective) unresponsiveness to hepatitis B virus (HBV) vaccination should also be included. There are several reports that, after HBV vaccination, naïve patients with CD on a gluten-containing diet have low titers of hepatitis B surface antibodies (HBsAb) and percentages of protective (>10 U/L) values lower than those in controls (2–5). The HBsAb response after an IM (3–7) or ID (8) booster normalizes after starting a proper gluten-free diet (GFD) (Table 1).
The HBsAb response seems to be associated with immunogenetic factors: multiple candidate genes have been implicated, including human leukocyte antigen phenotype DQ2, strongly linked to CD (4,9–11). The amount of gluten intake at vaccination has also been implicated (3).
The still worrying high prevalence of HBV infection in some industrialized and most developing countries requires pediatric gastroenterologists’ alertness to the relevance of poor HBV vaccine response in patients with CD. In fact, the latter could signal undiagnosed CD, requiring investigation of patients by specific antibody testing and/or duodenal biopsy and possible correction by an appropriate booster program during a strict GFD. On the contrary, every new diagnosis of CD in a previously HBV-vaccinated individual should trigger the evaluation of HBsAb titers to take appropriate action in case of nonresponse and to alert patients to their possible lack of full protection against HBV.
1. Husby S, Koletzko S, Korponay-Szabó IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr
2. Ertekin V, Tosun MS, Selimoglu MA. Is there need for a new hepatitis B vaccine schedule for children with celiac disease? Hepat Mon
3. Nemes E, Lefler E, Szegedi L, et al. Gluten intake interferes with the humoral immune response to recombinant hepatitis B vaccine in patients with celiac disease. Pediatrics
4. Ertem D, Gonen I, Tanidir C, et al. The response to hepatitis B vaccine: does it differ in celiac disease? Eur J Gastroenterol Hepatol
5. Blasco Alonso J, Espinosa MG, Navas VM, et al. Hepatitis B vaccine nonresponse in healthy and celiac children. Efficacy of single booster dose. Pediatrics Online
August 3, 2009.
6. Balamtekın N, Uslu N, Baysoy G, et al. Responsiveness of children with celiac disease to different hepatitis B vaccination protocols. Turk J Gastroenterol
7. Leonardi S, Spina M, Spicuzza L, et al. Hepatitis B vaccination failure in celiac disease: is there a need to reassess current immunization strategies? Vaccine
8. Leonardi S, Del Giudice MM, Spicuzza L, et al. Hepatitis B vaccine administered by intradermal route in patients with celiac disease unresponsive to the intramuscular vaccination schedule: a pilot study. Am J Gastroenterol
9. Park SD, Markowitz J, Pettei M, et al. Failure to respond to hepatitis B vaccine in children with celiac disease. J Pediatr Gastroenterol Nutr
10. Leonardi S, Longo R, Cotugno M, et al. Vaccination and celiac disease: results of a retrospective study (in Italian). Minerva Pediatr
11. Martinetti M, De Silvestri A, Belloni C, et al. Humoral response to recombinant hepatitis B virus vaccine at birth: role of HLA and beyond. Clin Immunol