Analysis of the humoral and cellular response after the third COVID‐19 vaccination in patients with autoimmune hepatitis

Abstract Background & Aims To explore the humoral and T‐cell response to the third COVID‐19 vaccination in autoimmune hepatitis (AIH). Methods Anti‐SARS‐CoV‐2 antibody titers were prospectively determined in 81 AIH patients and 53 healthy age‐ and sex‐matched controls > 7 days (median 35) after the first COVID‐19 booster vaccination. The spike‐specific T‐cell response was assessed using an activation‐induced marker assay (AIM) in a subset of patients. Results Median antibody levels were significantly lower in AIH compared to controls (10908 vs. 25000 AU/mL, p<0.001), especially in AIH patients treated with MMF (N=14, 4542 AU/mL, p=0.004) or steroids (N=27, 7326 AU/mL, p=0.020). Also, 48% of AIH patients had antibody titers below the 10% percentile of the healthy controls (9194 AU/mL, p<0.001). AIH patients had a high risk of failing to develop a spike‐specific T‐cell response (15/34 (44%) vs. 2/16 (12%), p=0.05) and showed overall lower frequencies of spike‐specific CD4+T cells (median: 0.074% vs 0.283;p=0.01) after the booster vaccination compared to healthy individuals. In 34/81 patients, antibody titers before and after booster vaccination were available. In this subgroup, all patients but especially those without detectable/low antibodies titers (<100 AU/mL) after the second vaccination (N=11/34) showed a strong, 148‐fold increase. Conclusion A third COVID‐19 vaccination efficiently boosts antibody levels and T‐cell responses in AIH patients and even seroconversion in patients with absent immune response after two vaccinations, but to a lower level compared to controls. Therefore, we suggest routinely assessing antibody levels in AIH patients and offering additional booster vaccinations to those with suboptimal response.