Hepatitis A vaccine immunogenicity in patients using immunosuppressive drugs: A systematic review and meta-analysis

Introduction: Inactivated hepatitis A (HepA) vaccines are very immunogenic in healthy individuals; however, it remains unclear how different immunosuppressive regimens affect HepA vaccine immunogenicity. Our objective was to summarise the current evidence on immunogenicity of HepA vaccination in patients using immunosuppressive drugs. Methods: We systematically searched the literature for studies on immunogenicity of inactivated HepA vaccines in adults using immunosuppressive drugs. Studies reporting seroconversion rates (SCR) 4–8 weeks after 1 and 2 doses of HepA vaccine in organ transplant recipients and patients with chronic inflammatory conditions were included in a meta-analysis. Results: We included 17 studies, comprising 1,332 individuals. In healthy controls (2 studies), SCRs were 90–94% after the first dose and 100% after the second dose. In organ transplant recipients, SCRs ranged from 0 to 67% after the first dose of vaccine and 0–97% after the second dose. In patients with chronic inflammatory conditions, SCRs ranged from 6% to 100% after the first dose and from 48 to 100% after the second dose of vaccine. Patients using a TNF-alpha inhibitor versus conventional immune-modulators (e.g. methotrexate, azathioprine, corticosteroids) were more likely to seroconvert after the first dose of vaccine (OR12.1 [2.14–68.2]) but not after the second dose of vaccine (OR 0.78 [0.21–2.92]) in a meta-analysis. Conclusion: Studies evaluating HepA vaccine immunogenicity in immunosuppressive agents are heterogeneous. Overall, there is an impaired immune response following HepA vaccination in patients using immunosuppressive drugs, especially after only one dose of vaccine and in organ transplant recipients. HepA vaccination should therefore be considered before immunosuppressive therapy. Future research should focus on alternative vaccination regimens and long-term immunogenicity. Prospero id: CRD42018102607