Autoimmune Hepatitis Following Vaccination for SARS-CoV-2 in Korea: Coincidence or Autoimmunity?

Autoimmune hepatitis (AIH) is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liver to be inflamed. AIH is one of the manifestations of a coronavirus disease 2019 (COVID-19), as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Few cases of AIH have been described after vaccination with two messenger RNA (mRNA)-based vaccines-BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)-against SARS-CoV-2. Herein, we report a case of AIH occurring after Pfizer-BioNTech COVID-19 vaccine. A 27-year-old female presented with jaundice and hepatomegaly, appearing 14 days after receiving the second dose of Pfizer-BioNTech vaccine. Her laboratory results showed abnormal liver function with high total immunoglobulin G level. She was diagnosed with AIH with histologic finding and successfully treated with oral prednisolone. We report an AIH case after COVID-19 vaccination in Korea.

Kang SH ，Kim MY ，Cho MY ，Baik SK ... -  《-》

Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.

Several vaccines have been developed for coronavirus disease 2019 (COVID-19) and are used worldwide. Here we report a case of severe acute hepatitis induced by COVID-19 vaccination. A 54-year-old woman received two doses of the Pfizer-BioNTech COVID-19 mRNA vaccine and an additional dose of the Moderna COVID-19 mRNA vaccine. Seven days after the third dose, she noticed fatigue, appetite loss and dark urine. Laboratory tests were consistent with severe liver injury and jaundice. Anti-smooth muscle antibody and HLA-DR4 were positive; thus, we suspected that she had autoimmune hepatitis (AIH). Intravenous methylprednisolone followed by oral prednisolone were administered. Because remission was not achieved, we performed percutaneous liver biopsy. Histologically, pan-lobular inflammation with moderate infiltration of lymphocytes and macrophages, interface hepatitis, and rosette formation were present. We regarded these findings as confirmation of the diagnosis of AIH. As she had not responded to corticosteroids, we added azathioprine. Liver biochemistry tests gradually improved, and prednisolone could be tapered without relapse of AIH. Dozens of cases of AIH after COVID-19 vaccination have been reported. Corticosteroids were effective in most cases, but some patients have died from liver failure after vaccination. This case illustrates the efficacy of azathioprine for steroid-refractory AIH induced by COVID-19 vaccination.

Ueno M ，Takabatake H ，Itakura J ，Fujita R ，Kayahara T ，Morimoto Y ，Notohara K ，Mizuno M ... -  《-》

SARS-CoV-2 vaccination and risk of severe COVID-19 outcomes in patients with autoimmune hepatitis.

Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. We included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10-0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11-0.35). SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.

Efe C ，Taşçılar K ，Gerussi A ，Bolis F ，Lammert C ，Ebik B ，Stättermayer AF ，Cengiz M ，Gökçe DT ，Cristoferi L ，Peralta M ，Massoumi H ，Montes P ，Cerda E ，Rigamonti C ，Yapalı S ，Adali G ，Çalışkan AR ，Balaban Y ，Eren F ，Eşkazan T ，Barutçu S ，Lytvyak E ，Zazueta GM ，Kayhan MA ，Heurgue-Berlot A ，De Martin E ，Yavuz A ，Bıyık M ，Narro GC ，Duman S ，Hernandez N ，Gatselis NK ，Aguirre J ，Idilman R ，Silva M ，Mendizabal M ，Atay K ，Güzelbulut F ，Dhanasekaran R ，Montano-Loza AJ ，Dalekos GN ，Ridruejo E ，Invernizzi P ，Wahlin S ... -  《-》

First report of post-transplant autoimmune hepatitis recurrence following SARS-CoV-2 mRNA vaccination.

Whilst vaccination for the SARS-CoV-2 virus has been successful in reducing the severity and burden of the COVID-19 pandemic, there have been recent reports of mRNA vaccines triggering autoimmune hepatitis in the native liver. There have been no descriptions thus far of recurrent 'autoimmune hepatitis' after liver transplantation in the context of SARS-CoV-2 vaccination. We describe a patient transplanted for autoimmune hepatitis who was stable for many years until they had immune-mediated flares coinciding with Pfizer-BioNTech mRNA vaccination. Intravenous steroid treatment was required to suppress histologically evident interface hepatitis. We firmly believe that mRNA vaccination was responsible for this 'recurrence' and that clinicians should be vigilant for this reaction in patients transplanted for autoimmune hepatitis.

Mahalingham A ，Duckworth A ，Griffiths WJH 《-》

Autoimmune hepatitis after SARS-CoV-2 vaccine: New-onset or flare-up?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been reported to trigger several autoimmune diseases. There are also recent reports of autoimmune diseases that develop after SARS-CoV-2 vaccines. Autoimmune hepatitis is a polygenic multifactorial disease, which is diagnosed using a scoring system. A 61-year-old woman presented with malaise, fatigue, loss of appetite, nausea and yellow eyes. She had a Pfizer/BioNTech BNT162b2 mRNA vaccine a month ago. Her physical examination revealed jaundice all over the body, especially in the sclera. The laboratory tests showed elevated liver enzymes and bilirubin levels. Antinuclear antibody and anti-smooth muscle antibody were positive and immunoglobulin G was markedly elevated. The liver biopsy revealed histopathological findings consistent with autoimmune hepatitis (AIH). The patient was diagnosed with AIH and initiated on steroid therapy. She rapidly responded to steroid therapy. A few cases of AIH have been reported after the COVID-19 vaccine so far. Although the exact cause of autoimmune reactions is unknown, an abnormal immune response and bystander activation induced by molecular mimicry is considered a potential mechanism, especially in susceptible individuals. As intensive vaccination against SARS-CoV-2 continues, we would like to emphasize that clinicians should be cautious and consider AIH in patients presenting with similar signs and symptoms.

Avci E ，Abasiyanik F 《-》