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

Abstract

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.

Fig. 1

Transaminases (Panel A) and bilirubin (Panel B) serum levels.

Fig. 2

Indirect immunofluorescence on rodent tissue, VSM47 and HEp2 cells. The staining of the mitochondria-rich distal renal tubules (Panel A) and of the gastric parietal cells (Panel B) is compatible with anti-mitochondrial antibody (AMA), a specificity however negative at molecular level (see text). Panel C shows a positive rim-like staining of the nuclei (rim-like anti-nuclear antibody (ANA)) in the liver. Panel D (VSM47) and Panel E (HEp2 cells) confirm a rim-like ANA and show a trabecular staining of the cytoplasm. A speckled pattern is also visible in the nuclei of Panels D and E.

Fig. 3

Liver biopsy findings. Panel A and B: expanded portal tracts with intense lymphoplasmacytic infiltrate with scattered eosinophils, and interface hepatitis (HE; Panel A 10x, Panel B 20x). Panel C: higher magnification of interface hepatitis (HE 40x). Panel D: intense lobular activity associated with centrilobular necrosis (HE 40x). Panel E: CD38 staining showing plasma cellular infiltrate, also affecting the interface (20x). Courtesy of Luca Mazzucchelli and Elisabetta Merlo, Istituto Cantonale di Patologia EOC, Locarno, Switzerland.