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.

Immune-mediated hepatitis with the Moderna vaccine, no longer a coincidence but confirmed

“…In three cases there were features suggesting coincidental autoimmune hepatitis: 35-year-old lady in her third trimester of pregnancy with positive double stranded DNA, an 80-year-old lady with a history of autoimmune conditions and a 41-year-old lady with strongly positive auto-antibody panel after both doses of vaccination. In the other four cases, a raised IgG, with at least one positive antibody was noted in three cases ( 4) , 5) , 6) , 7) ).…”

“…7 cases of suspected immune-mediated hepatitis have been reported with SARS-2-COV mRNA vaccines (three with Pfizer and four with Moderna) ( 1) , 2) , 3) , 4) , 5) , 6) , 7) ). Liver histology was assessed in every case and findings were similar to ours indicating acute hepatitis with interface hepatitis, lymphoplasmacytic infiltrate and absence of fibrosis.…”

“…We have read with interest the recent cases suggesting the possibility of vaccine-induced immune-mediated hepatitis with Pfizer-BioNTech and Moderna mRNA-1273 mRNA vaccines for the SARS-CoV-2 virus. ( 1) , 2) , 3) , 4) , 5) , 6) , 7) ). However, as the cohort of vaccinated individuals against COVID-19 increases, the previously reported cases could not exclude a coincidental development of autoimmune hepatitis, which has an incidence of 3/100 000 population per year ( 8 ).…”

COVID-19 vaccine and autoimmunity. A new case of autoimmune hepatitis and review of the literature

“…Findings in liver biopsy correlate with reports of AIH following SARS-CoV-2 vaccination. Necroinflammatory hepatitis was observed in all cases of AIH following vaccination with Moderna mRNA-1273 COVID-19 [ [24] , [25] , [26] , [27] , [28] , [29] ], Pfizer-BioNTech mRNA vaccine [ [30] , [31] , [32] , [33] ], and AstraZeneca ChAdOx1 nCoV-19 vaccine [ 8 , 34 ]. It has been suggested that portal infiltration with eosinophils correlates with drug-induced liver injury, including vaccines (i.e., Moderna mRNA-1273 and AstraZeneca ChAdOx1 nCoV-19 vaccines) [ 8 , 27 , 28 ].…”

Sudden onset of vitiligo after COVID‐19 vaccine

“…Since vitiligo is a common pigmentary disorder afflicting 0.5%–2% of the world population 8 and COVID vaccination nowadays is a common practice, the possibility that the onset of vitiligo after vaccination is just a coincidence should also be considered. However, the temporal relationship between the vaccine and development of the disease and the instances of autoimmune phenomena manifesting after COVID‐19 vaccination, 1 , 2 , 5 , 6 suggest that the vaccine could play a role in triggering vitiligo.…”