Autoimmune hepatitis developing after SARS-CoV-2 vaccination: series of three cases

G Rasschaert, Silke François, A Verbeeck, M Schils, M Aerts, P Lesfevre, I Colle, Hendrik Reynaert

Onderzoeksoutput: Meeting abstract (Journal)

Samenvatting

We present a series of three patients with an assumed diagnosis of autoimmune hepatitis (AIH) after SARS-CoV-2 vaccination. A 57-year-old woman was referred for progressive elevation of liver function tests (LFTs) four weeks following the first dose of Moderna mRNA-1273 vaccination. Medical history included Hashimoto’s thyroiditis and SARS-CoV-2 infection six months earlier with a mild disease course. She did not take medication or herbal supplements. No substance abuse was recorded. LFTs were normal one month before vaccination. Physical examination was unremarkable. At referral, laboratories were significant for aspartate aminotransferase (AST) (22xULN), alanine aminotransferase (ALT) (38xULN), alkaline phosphatase (AP) (1.3xULN) and gamma-glutamyl transpeptidase (GGT) (3xULN). Hepatitis A, B, C and E virus markers, HIV, Cytomegalovirus, Epstein-Barr, Herpes simplex type 1 and 2 serology were negative. Ceruloplasmin and α1-antitrypsin levels were normal. Anti-mitochondrial, anti-smooth muscle, anti-liver-kidney microsomal antibodies were negative, while antinuclear antibody (ANA) was positive (1:320, speckled pattern). Total IgG was normal. Abdominal ultrasound was unremarkable. Histology showed interface activity including a mixed inflammatory infiltrate with predominant lymphocytes, focal rosetting was observed. According to the International Autoimmune Hepatitis Group (IAIHG) criteria, pre-treatment score was 19, accounting for definite AIH. Immunosuppression was not immediately started due to slow but progressive decrease of LFTs. However, six weeks later budesonide 9mg was initiated for an increase in LFTs (transaminases x10 ULN). Lack of efficacy necessitated a shift towards methylprednisolone 32mg after one month. Azathioprine 50mg was associated two weeks later. Currently she is doing well with marginal AST and ALT elevation (<1.5ULN) and ANA normalisation. In the future, we will continue to treat her according to the standard of care for AIH. A 53-year-old man consulted for silent icterus since four days, seven days after completing the schedule of Pfizer-BioNTech BNT162b2 mRNA vaccination. He denied smoking, alcohol and medication use and had a negative medical history. LFTs were normal six weeks before vaccination. There was no previous SARS-CoV-2 infection. Physical examination showed jaundice. Laboratories were significant for AST (48xULN), ALT (95xULN), AP (2xULN) and GGT (12xULN). Total bilirubin was 3.1g/dL (direct 2.8mg/dL). Viral serology was negative. Ceruloplasmin and α1-antitrypsin levels were normal. Auto-immune panel showed positive ANA (1:80, speckled pattern). Total IgG was normal. Abdominal ultrasound observed steatosis. Histology was similar to the first patient. According to IAIHG criteria, pre-treatment score was 13, accounting for probable AIH. Spontaneous LFT improvement was appreciated two weeks following presentation. A 39-year-old woman was referred for LFT alterations four weeks after her first dose of Pfizer-BioNTech BNT162b2 mRNA vaccination. She had a medical history of Hashimoto’s thyroiditis and rheumatoid arthritis. LFTs were normal seven months before vaccination. She reported alcohol (5 units/week) and tobacco consumption (12 cigarettes/day). No over the counter drugs were reported. There was no documented previous SARS-CoV-2 infection. Physical examination was unremarkable. Laboratories were significant for AST (11x ULN), ALT (17x ULN), and GGT (1.2x ULN). Viral serology was negative. Ceruloplasmin and α1- antitrypsin levels were normal. The auto-immune panel was negative. Total IgG was normal. Abdominal ultrasound showed mild steatosis. Histology disclosed interface hepatitis and predominant lymphocyte infiltration without biliary changes. According to IAIHG criteria, pre-treatment score was 16, accounting for definite AIH. Immunosuppressive therapy with methylprednisolone (32mg) and azathioprine (100mg) was initiated after work up, about eight weeks after documentation of LFT alteration. At that time there was a continued increase of LFT alterations with a bilirubinaemia of almost 4.0g/dL. An adequate response was observed. With her treatment of methylprednisolone 8mg and azathioprine 100mg, LFTs almost completely normalised. Above, we described the onset of AIH after vaccination with different mRNA SARS-CoV-2 vaccines in three patients. It is accepted AIH can be triggered by a plethora of viruses and drugs. Additionally, past reports have attributed development of AIH to prior vaccination suggesting a potential role of both virus and vaccine in revealing AIH in predisposed individuals. So far there is no pathophysiological link between SARSCoV-2 vaccines and AIH. One hypothesis is molecular mimicry. In vitro data demonstrates spike protein S1 antibodies (for which the mRNA codes) have high affinity against transglutaminase 3, transglutaminase 2, anti-extractable nuclear antigen, nuclear antigen and myelin basic protein. So far, only a handful of similar cases are reported in literature. Important questions are raised concerning the safety of booster vaccination.
Originele taal-2English
ArtikelnummerY05
Pagina's (van-tot)55
Aantal pagina's1
TijdschriftActa Gastro-Enterologica Belgica
Volume85
Nummer van het tijdschrift1
StatusPublished - jan 2022
EvenementBelgian Week of Gastroenterology - online
Duur: 9 feb 202211 feb 2022

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