June 16, 2023

Individuals diagnosed with inflammatory bowel disease (IBD) or celiac disease (CD) are presumed to have a suboptimal humoral response to the hepatitis B virus (HBV) vaccine. For this reason, multiple clinical guidelines recommend screening patients with IBD or CD for HBV immunity and revaccinating patients when titers are low. A lack of high-quality studies supporting these recommendations, however, has affected clinicians' adherence to testing anti-hepatitis B surface antigen antibody (anti-HBs) levels in these patients.

In a population-based cohort study published in Clinical Gastroenterology and Hepatology in 2023, Mayo Clinic researchers sought to assess the effectiveness of HBV vaccination, including the rates of both HBV immunity and infection, among patients with IBD or CD who were previously vaccinated. The researchers also assessed the effect of time on anti-HBs levels after vaccination.

Imad Absah, M.D., a lead author on the Clinical Gastroenterology and Hepatology article, explains the challenge driving this research. Dr. Absah is a pediatric gastroenterologist and pediatrician at Mayo Clinic in Rochester, Minnesota.

"Currently, patients with IBD and celiac disease are checked for hepatitis B immunity before they start treatment. If their antibody titers are low, the guidelines recommend revaccination and repeat blood tests to document immunity or adequate levels of protective titers. This can result in delay of treatment, extra vaccination and blood tests," says Dr. Absah.

Study methods

The researchers conducted a retrospective cohort study of residents of Olmsted County, Minnesota, with the following study groups. The first study group (IBD/CD group) included 351 individuals who met these criteria: diagnosed with IBD or CD from Jan. 1, 2000, through Dec. 31, 2019 (defined as index date); received two or more HBV vaccines before their index date; underwent HBV screening after their index date.

The researchers also identified two separate population-based comparison groups of age- and sex-matched individuals without a history of IBD or CD at the index date.

• Group 1 included 3,102 Olmsted County residents of all ages who met these criteria: received two or more HBV vaccinations; had anti-HBs titers measured from Jan. 1, 2000, through Dec. 31, 2021; had at least one anti-HBs titer measured anytime after the last documented HBV vaccination.
• Group 2 included five randomly selected residents who were sex matched and age matched to each individual in the IBD/CD group.

Results

Overall, the researchers documented that individuals in the IBD/CD group and the comparison groups had a comparable response to HBV vaccination. They observed no evidence of increased HBV risk in patients with IBD or CD who were fully vaccinated for HBV.

Within the IBD/CD group, HBV-protective titers (≥ 10 mIU/mL) decreased with time before plateauing.

• Forty-five percent of individuals had protective titer levels 5 to 10 years after HBV vaccination.
• Forty-one percent of individuals had protective titer levels 15 to 20 years after HBV vaccination after the last HBV vaccination.

Within the comparison groups, HBV-protective titers also decreased over time. But 15 years after the last HBV vaccination, the protective titer levels in the comparison groups remained consistently higher than the levels found in the IBD/CD group. The researchers note that this difference was not associated with an increased risk of HBV infection among IBD/CD group members who received HBV vaccination before they were diagnosed with a gastrointestinal disease. No new HBV infection developed in the IBD/CD group during a median follow-up of 9.4 years.

Conclusions

According to Dr. Absah and co-authors, these results suggest that routine testing of anti-HBs titers may not be indicated for all patients with IBD or CD who are fully vaccinated for HBV.

"This study along with our previous work on celiac disease and hepatitis B immunity clearly shows that low titers in fully vaccinated patients may not indicate that these patients lack immunity," says Dr. Absah. "Fully vaccinated patients with IBD and celiac in our study had no evidence of increased risk of hepatitis B infection, and the trend in their immunity titers was similar to those found in the general population."

Dr. Absah notes that the next step in research will seek to identify the best method for evaluating an individual's immunity against hepatitis B and explore whether tests measuring cellular immunity rather than antibody levels yield more-useful information.

For more information

Ulrich JA, et al. Effectiveness of hepatitis B vaccination for patients with inflammatory bowel and celiac disease. Clinical Gastroenterology and Hepatology. In press.

Refer a patient to Mayo Clinic.