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Letters to the Editor

Children Unresponsive to Hepatitis B Virus Vaccination Also Need Celiac Disease Testing

Vajro, Pietro*; Paolella, Giulia*; Nobili, Valerio

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Journal of Pediatric Gastroenterology and Nutrition: October 2012 - Volume 55 - Issue 4 - p e131
doi: 10.1097/MPG.0b013e31825d4ac9
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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).

Response to HBV vaccination (HBsAb > 10 IU/L) in pediatric patients with celiac disease compared with age-matched controls

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 2012; 54:136–160.
2. Ertekin V, Tosun MS, Selimoglu MA. Is there need for a new hepatitis B vaccine schedule for children with celiac disease? Hepat Mon 2011; 11:634–637.
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 2008; 121:e1570–e1576.
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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 2010; 105:2117–2119.
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 2007; 44:431–435.
10. Leonardi S, Longo R, Cotugno M, et al. Vaccination and celiac disease: results of a retrospective study (in Italian). Minerva Pediatr 2011; 63:363–367.
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 2000; 97:234–240.
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