Analysis of the Humoral and Cellular Response After the Third COVID-19 Vaccination in Patients With Autoimmune Hepatitis

Johannes Hartl; Darius Ferenc Rüther; Paul Maria Duengelhoef; Thomas Theo Brehm; Silja Steinmann; Jan Philipp Weltzsch; Fabian Glaser; Martina Sterneck; Marcial Sebode; Christina Weiler-Normann; Marc Lütgehetmann; Golda Melina Schaub; Friedrich Haag; Christoph Schramm; Julian Schulze zur Wiesch; Ansgar Wilhelm Lohse


Liver International. 2023;43(2):393-400. 

In This Article

Abstract and Introduction


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 (10 908 vs. 25 000 AU/ml, p < .001), especially in AIH patients treated with MMF (N = 14, 4542 AU/ml, p = .004) or steroids (N = 27, 7326 AU/ml, p = .020). Also, 48% of AIH patients had antibody titers below the 10% percentile of the healthy controls (9194 AU/ml, p < .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 = .05) and showed overall lower frequencies of spike-specific CD4 + T cells (median: 0.074% vs 0.283; p = .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 the 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 responses.


Various reports show a reduced immune response to COVID-19 vaccinations in patients on immunosuppression,[1] including liver transplant recipients.[2] Moreover, we have reported recently that AIH patients show an impaired B- and T-cell response after the second COVID-19 vaccination, even in the absence of or under mild immunosuppressive treatment.[3] Also, AIH patients seemed to have an increased risk to acquire SARS-CoV-2 infection.[3] At the same time, immunosuppressive drugs[4,5] and advanced stages of chronic liver diseases[6] are associated with a more severe course of COVID-19. Additionally, various SARS-CoV-2 variants have been identified as being partly resistant to antibody-mediated neutralization requiring induction of higher antibody titers for protection.[5–7] Indeed, the third dose of a COVID-19 vaccine demonstrated effectiveness for boosting the vaccination response and preventing severe outcomes in the general population and patients under immunosuppression like solid organ transplant recipients or patients with a rheumatic disease.[8–10]

In this prospective observational study, we aimed to explore the humoral and T-cell response after the third COVID-19 vaccination in patients with AIH compared to healthy controls in a real-world setting.