Acute autoimmune-like hepatitis with atypical anti-mitochondrial antibody after mRNA COVID-19 vaccination: A novel clinical entity?

J Autoimmun. 2021 Sep;123:102706. doi: 10.1016/j.jaut.2021.102706. Epub 2021 Jul 15.


Autoimmune phenomena and clinically apparent autoimmune diseases, including autoimmune hepatitis, are increasingly been reported not only after natural infection with the SARS-CoV-2 virus, but also after vaccination against it. We report the case of a 63-year old man without a history of autoimmunity or SARS-CoV-2 natural infection who experienced acute severe autoimmune-like hepatitis seven days after the first dose of the mRNA-1273 SARS-CoV-2 vaccine. Liver histology showed inflammatory portal infiltrate with interface hepatitis, lobular and centrilobular inflammation with centrilobular necrosis, in absence of fibrosis and steatosis. Serum immunoglobulin G was slightly elevated. Autoimmune liver serology showed an indirect immunofluorescence pattern on triple rodent tissue compatible with anti-mitochondrial antibody (AMA), but, unexpectedly, this pattern was not mirrored by positivity for primary biliary cholangitis (PBC)-specific molecular tests, indicating that this antibody is different from classical AMA. Anti-nuclear antibody (ANA) was also positive with a rim-like indirect immunofluorescence pattern on liver and HEp2 cell substrates, similar to PBC-specific ANA; however, anti-gp210 and a large panel of molecular-based assays for nuclear antigens were negative, suggesting a unique ANA in our patient. He carries the HLA DRB1*11:01 allele, which is protective against PBC. Response to prednisone treatment was satisfactory. The clinical significance of these novel specificities needs to be further evaluated in this emerging condition.

Keywords: Atypical anti-mitochondrial antibody; Autoimmune-like hepatitis; SARS-Cov-2; mRNA vaccine.

Publication types

  • Case Reports
  • Review

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273
  • Animals
  • Antibodies, Antinuclear / immunology
  • Antibody Specificity
  • Autoantibodies / immunology*
  • Autoantigens / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / adverse effects*
  • Cell Line
  • Fluorescent Antibody Technique, Indirect
  • HLA-DRB1 Chains / immunology*
  • Hepatitis, Autoimmune / drug therapy
  • Hepatitis, Autoimmune / etiology*
  • Hepatitis, Autoimmune / immunology
  • Hepatitis, Autoimmune / pathology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Liver / immunology
  • Liver / pathology
  • Male
  • Middle Aged
  • Mitochondria / immunology*
  • Prednisone / therapeutic use
  • Rosuvastatin Calcium / adverse effects
  • Rosuvastatin Calcium / therapeutic use
  • SARS-CoV-2 / immunology*
  • Vaccination / adverse effects*


  • Antibodies, Antinuclear
  • Autoantibodies
  • Autoantigens
  • COVID-19 Vaccines
  • HLA-DRB1 Chains
  • HLA-DRB1*11:01 antigen
  • Immunosuppressive Agents
  • Rosuvastatin Calcium
  • 2019-nCoV Vaccine mRNA-1273
  • Prednisone