Incidence of Low Seroimmunity to Hepatitis B Virus in Children With Inflammatory Bowel Disease
Corresponding Author
Abhishek Watts
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Address correspondence and reprint requests to Abhishek Watts, MD, 705 Riley Hospital Drive, ROC 4210, Indianapolis, IN 46202 (e-mail: [email protected]).Search for more papers by this authorWilliam E. Bennett
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Section of Pediatric and Adolescent Comparative Effectiveness Research, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorJean P. Molleston
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorSandeep K. Gupta
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorJoseph M. Croffie
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorShamaila Waseem
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorBrian A. McFerron
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorSteven J. Steiner
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorSanjay Kumar
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorCharles P. Vanderpool
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorEmily C. Hon
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorMolly A. Bozic
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorGirish C. Subbarao
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorMarian D. Pfefferkorn
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorCorresponding Author
Abhishek Watts
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Address correspondence and reprint requests to Abhishek Watts, MD, 705 Riley Hospital Drive, ROC 4210, Indianapolis, IN 46202 (e-mail: [email protected]).Search for more papers by this authorWilliam E. Bennett
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Section of Pediatric and Adolescent Comparative Effectiveness Research, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorJean P. Molleston
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorSandeep K. Gupta
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorJoseph M. Croffie
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorShamaila Waseem
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorBrian A. McFerron
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorSteven J. Steiner
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorSanjay Kumar
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorCharles P. Vanderpool
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorEmily C. Hon
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorMolly A. Bozic
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorGirish C. Subbarao
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorMarian D. Pfefferkorn
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorThe authors report no conflicts of interest.
ABSTRACT
Objectives:
Patients with inflammatory bowel disease (IBD) often receive immunosuppressive therapy, which may make them vulnerable to infections such as hepatitis B. We hypothesized that hepatitis B virus titers are low in the vaccinated pediatric population with IBD. The aims of our study were to identify the incidence of lower titers of hepatitis B surface antibody (HBsAb) and determine which patient factors may be associated with lower HBsAb titers.
Methods:
Patients with diagnosis of IBD, ages 5 to 18 years, were prospectively enrolled. Patients were confirmed to have had a full series of hepatitis B vaccination. Quantitative serum HBsAb titers were measured and logistic regression analysis with independent variables of age, sex, race, disease phenotype, surgery, medications and a dependent variable of adequate HBsAb titers (> 10 mIU/mL) was performed.
Results:
Of the 116 patients enrolled, 57 were boys and 59 were girls. 75 patients had a diagnosis of Crohn disease; 32 had a diagnosis of ulcerative colitis; and 9 patients had been diagnosed as having indeterminate colitis. At the time of the study, 15 patients were taking corticosteroid, 66 on an immunomodulator, and 53 on a biologic. Sixty percent of patients in the 5- to 10-year age group had protective titers versus 22% to 27% in the older groups, P = 0.04. Only 28% of the 116 patients had HBsAb titers of >10m IU/mL. Twenty percent of the patients taking corticosteroids, 27% taking immunomodulators, and 24% taking biologics were found to be seroimmune.
Conclusions:
Nearly two-thirds of pediatric patients with IBD have low titers against hepatitis B virus. Titers were highest in the younger patients. No patient-specific variable, such as the use of immunosuppressants, appeared to influence these low titers.
REFERENCES
- 1.Millonig G, Kern M, Ludwiczek O, et al. Subfulminant hepatitis B after infliximab in Crohn's disease: need for HBV-screening? World J Gastroenterol 2006; 12: 974–976.
- 2.Madonia S, Orlando A, Scimeca D, et al. Occult hepatitis B and infliximab-induced HBV reactivation. Inflamm Bowel Dis 2007; 13: 508–509.
- 3.Ali T, Yun L, Shapiro D, et al. Viral infections in patients with inflammatory bowel disease on immunosuppressants. Am J Med Sci 2012; 343: 227–232.
- 4.Esteve M, Saro C, Gonzalez-Huix F, et al. Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis. Gut 2004; 53: 1363–1365.
- 5.Hou JK, Velayos F, Terrault N, et al. Viral hepatitis and inflammatory bowel disease. Inflamm Bowel Dis 2010; 16: 925–932.
- 6.Coates T, Wilson R, Patrick G, et al. Hepatitis B vaccines: assessment of the seroprotective efficacy of two recombinant DNA vaccines. Clin Ther 2001; 23: 392–403.
- 7.Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep 2006; 55: 1–33.
- 8.Hepatitis B vaccines: WHO position paper-recommendations. Vaccine 2010; 28: 589–590.
- 9.Shouval D. Hepatitis B vaccines. J Hepatol 2003; 39: S70–76.
- 10.Alfaleh F, Alshehri S, Alansari S, et al. Long-term protection of hepatitis B vaccine 18 years after vaccination. J Infect 2008; 57: 404–409.
- 11.Bialek SR, Bower WA, Novak R, et al. Persistence of protection against hepatitis B virus infection among adolescents vaccinated with recombinant hepatitis B vaccine beginning at birth: a 15-year follow-up study. Pediatr Infect Dis J 2008; 27: 881–885.
- 12.Gabbuti A, Romano L, Blanc P, et al. Long-term immunogenicity of hepatitis B vaccination in a cohort of Italian healthy adolescents. Vaccine 2007; 25: 3129–3132.
- 13.Gilca V, De Serres G, Boulianne N, et al. Antibody persistence and the effect of a booster dose given 5, 10 or 15 years after vaccinating preadolescents with a recombinant hepatitis B vaccine. Vaccine 2013; 31: 448–451.
- 14.Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2011; 53: 68–75.
- 15.Wainwright RB, Bulkow LR, Parkinson AJ, et al. Protection provided by hepatitis B vaccine in a Yupik Eskimo population-results of a 10-year study. J Infect Dis 1997; 175: 674–677.
- 16.Lu Y, Jacobson D, Bousvaros A. Immunizations in patients with inflammatory bowel disease. Inflamm Bowel Dis 2009; 15: 1417–1423.
- 17.Hagihara Y, Ohfuji S, Watanabe K, et al. Infliximab and/or immunomodulators inhibit immune responses to trivalent influenza vaccination in adults with inflammatory bowel disease. J Crohns Colitis 2014; 8: 223–233.
- 18.Viget N, Vernier-Massouille G, Salmon-Ceron D, et al. Opportunistic infections in patients with inflammatory bowel disease: prevention and diagnosis. Gut 2008; 57: 549–558.
- 19.Moses J, Alkhouri N, Shannon A, et al. Hepatitis B immunity and response to booster vaccination in children with inflammatory bowel disease treated with infliximab. Am J Gastroenterol 2012; 107: 133–138.
- 20.Gisbert JP, Villagrasa JR, Rodriguez-Nogueiras A, et al. Efficacy of hepatitis B vaccination and revaccination and factors impacting on response in patients with inflammatory bowel disease. Am J Gastroenterol 2012; 107: 1460–1466.
- 21.Gisbert JP, Chaparro M, Esteve M. Review article: prevention and management of hepatitis B and C infection in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33: 619–633.
- 22.Rahier JF, Ben-Horin S, Chowers Y, et al. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2009; 3: 47–91.
- 23.Altunoz ME, Senates E, Yesil A, et al. Patients with inflammatory bowel disease have a lower response rate to HBV vaccination compared to controls. Dig Dis Sci 2012; 57: 1039–1044.
- 24. Wiley-Blackwell, Cunningham M, Foster GR, Irving P, Siegel CA, Rampton D, Shanahan F. What to do about Hepatitis B and Hepatitis C in patients with IBD. Clinical Dilemmas in Inflammatory Bowel Disease 2011; 23–6.
- 25.Nordgaard-Lassen I, Dahlerup JF, Belard E, et al. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment. Dan Med J 2012; 59: c4480.
- 26.Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009; 50: 661–662.
- 27.Gisbert JP, Villagrasa JR, Rodriguez-Nogueiras A, et al. Kinetics of anti-hepatitis B surface antigen titers after hepatitis B vaccination in patients with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19: 554–558.
- 28.Are booster immunisations needed for lifelong hepatitis B immunity? European Consensus Group on Hepatitis B Immunity. Lancet 2000; 355: 561–565.
- 29.WHO position paper - recommendations. Vaccine 2009; 28: 589–590.
- 30.Austin PC, Steyerberg EW. The number of subjects per variable required in linear regression analyses. J Clin Epidemiol 2015; 68: 627–636.
- 31.Salinas GF, De Rycke L, Barendregt B, et al. Anti-TNF treatment blocks the induction of T cell-dependent humoral responses. Ann Rheum Dis 2013; 72: 1037–1043.
- 32.Petersen KM, Bulkow LR, McMahon BJ, et al. Duration of hepatitis B immunity in low risk children receiving hepatitis B vaccinations from birth. Pediatr Infect Dis J 2004; 23: 650–655.
- 33.McMahon BJ, Dentinger CM, Bruden D, et al. Antibody levels and protection after hepatitis B vaccine: results of a 22-year follow-up study and response to a booster dose. J Infect Dis 2009; 200: 1390–1396.
- 34.Bruce MG, Bruden D, Hurlburt D, et al. Antibody levels and protection after hepatitis B vaccine: results of a 30-year follow-up study and response to a booster dose. J Infect Dis 2016; 24: 16–22.
10.1093/infdis/jiv748 Google Scholar
- 35.Belle A, Baumann C, Bigard MA, et al. Impact of immunosuppressive therapy on hepatitis B vaccination in inflammatory bowel diseases. Eur J Gastroenterol Hepatol 2015; 27: 877–881.
- 36.Cossio-Gil Y, Martinez-Gomez X, Campins-Marti M, et al. Immunogenicity of hepatitis B vaccine in patients with inflammatory bowel disease and the benefits of revaccination. J Gastroenterol Hepatol 2015; 30: 92–98.
- 37.deBruyn J, Soon IS, Feng S, et al. Serologic protection to and completion of vaccinations in children with inflammatory bowel disease: P-148. Inflamm Bowel Dis 2012; 18: S74.
- 38.Recommended adult immunization schedule: United States, 2010. Ann Intern Med 2010; 152: 36–39.
- 39.Rey D, Krantz V, Partisani M, et al. Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load. Vaccine 2000; 18: 1161–1165.