Autoimmune diseases after hepatitis B immunization in adults: Literature review and meta-analysis, with reference to 'autoimmune/autoinflammatory syndrome induced by adjuvants' (ASIA)

Vaccine. 2018 Sep 11;36(38):5796-5802. doi: 10.1016/j.vaccine.2018.07.074. Epub 2018 Aug 9.


Background: To assess if hepatitis B vaccination in adults is causally associated with autoimmune diseases. Such causation has been claimed based mainly on case reports and uncontrolled studies, and a syndrome 'Autoimmune/autoinflammatory Disorder Induced by Adjuvants' (ASIA) has been claimed to be linked to immunization, particularly hepatitis B vaccination.

Methods: Review of peer-reviewed literature from January 1990 to March 2017 identifying controlled studies with documented incidence of autoimmune diseases occurring after hepatitis B vaccinations in adults. From 1297 studies identified, 259 were further assessed and 49 reviewed further; 19 relevant papers reporting 21 results are reviewed here, and 14 results included in a meta-analysis.

Results: Overall no association between hepatitis B vaccination and the onset of autoimmune diseases was seen. The overall odds ratio was 1.06, with 95% confidence limits of 0.93-1.21, with non-significant heterogeneity. Only one study showed a significant excess risk between hepatitis B immunisation and autoimmune disease.

Conclusions: Despite multiple case reports, there is no reliable scientific evidence of autoimmune diseases being caused by hepatitis B vaccinations.

Keywords: ASIA syndrome; Autoimmune disease; Case-control study; Cohort study; Hepatitis B; Meta-analysis; New Zealand; Vaccination.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adjuvants, Immunologic / adverse effects*
  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / immunology
  • Hepatitis B / prevention & control
  • Hepatitis B Vaccines / adverse effects*
  • Hepatitis B Vaccines / immunology
  • Humans
  • Vaccination / adverse effects*


  • Adjuvants, Immunologic
  • Hepatitis B Vaccines