ABSTRACT
In a fraction of SARS-CoV-2 vaccinees, hepatitis compatible with features of autoimmune hepatitis (AIH) have been observed. However, it remains unclear whether the association is coincidental, reflects drug-induced liver injury, or involves vaccine-induced antigen-specific immune activation. Here, we report a case of a 52-year-old male developing a transient hepatitis after the first mRNA vaccination and severe AIH-compatible hepatitis after the second. The intrahepatic immune cell infiltrate was analysed by highly multiplexed imaging mass cytometry broadly covering key immune cell populations. Liver and longitudinal blood samples were analysed for the presence and phenotype of SARS-CoV-2 Spike-specific CD8 T cells using MHC class I tetramer technology. Additionally, Serum titers against SARS-Cov2-Spike antibodies were assessed. We identified a panlobular CD8 T cell dominant immune cell infiltrate in the liver without significant plasma cell components. Spike-specific CD8 T cells were highly enriched within the intrahepatic CD8 T cell population expressing activation markers and a tissue-resident phenotype. The activation phenotype correlated with the circulating Spike-specific CD8 T cell profile and longitudinal analysis revealed a rapid decline of T cell activation after the initiation of budesonid therapy. However, the patient experienced a mild relapse under therapy that was paralleled by the peripheral activation of Spike-specific CD8 T cells and was controlled under systemic steroid therapy. Collectively, our results indicate that an immune-mediated hepatitis after COVID19 vaccination can present with typical clinical features of an AIH but can be pathophysiologically separated from a classical AIH. Whether a long-term immunosuppressive regimen will be required remains to be determined.