Autoimmune liver diseases and SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.

Autoimmune Hepatitis-Like Syndrome Following COVID-19 Vaccination: A Systematic Review of the Literature.

OBJECTIVES: During the summer of 2021, case reports began to emerge documenting a small number of individuals who developed autoimmune hepatitis (AIH) following COVID-19 vaccination. These cases are rare and novel, and very little is known. In our systematic review, we analyzed every published case of AIH and reviewed their characteristic findings, treatment, and outcomes. METHODS: We searched PubMed, Embase, and Web of Science from December 1, 2019, to November 1, 2021. Two researchers independently extracted information from the articles about vaccine type, patient history, laboratory values, histology results, treatment regimens, and disease course. RESULTS: Thirty-two patients developed AIH-like syndromes after receiving a COVID-19 vaccine. Jaundice was the most frequently reported symptom (81%), and 19% of patients were initially asymptomatic and presented with elevated liver enzymes found during routine bloodwork. Mean alanine transaminase, aspartate transaminase, and total bilirubin were 1231 U/L, 921 U/L, and 14 mg/dL, respectively. Anti-nuclear antibody was positive in 56%, and anti-smooth muscle antibody in 28% of patients. Steroids were used in 75% of patients. Improvement or complete resolution was seen in 97% of patients. One patient died despite aggressive steroid treatment. CONCLUSION: COVID-19 vaccine-induced AIH is an uncommon association with just 32 documented cases in the literature. Clinicians should be vigilant for AIH in patients who present with liver injury following vaccination. These new findings should under not deter individuals from getting vaccinated, as the benefits of vaccination far outweigh the risks. Fortunately, COVID-19 vaccine-induced AIH appears amendable to corticosteroid therapy and appears to have a favorable outcome.

Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome.

BACKGROUND AND AIMS: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. APPROACH AND RESULTS: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. CONCLUSIONS: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.

[Autoimmune Hepatitis - What is important for clinical practice?] / Autoimmune Hepatitis ­ Was ist wichtig für die Praxis?

Autoimmune hepatitis is a rare but chronic autoimmune-mediated liver disease. Key features are elevated transaminases, hypergammaglobulinemia, presence of specific autoantibodies and typical histological features. Diagnostic scores are helpful in establishing the diagnosis. Immunosuppressive therapy should be initiated in every patient with inflammatory activity. First-line therapy includes steroids and azathioprine and results in biochemical and histological remission in the majority of patients. In most cases, lifelong therapy is required. Every patient should receive regular follow-up surveillance including biochemical parameters as well as sonography and elastography.

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.

SARS-CoV-2 vaccine, a new autoimmune hepatitis trigger?

SARS-CoV2 infection and vaccination against this virus have been related to the development of autoimmune diseases. We report a case of autoimmune hepatitis (AIH) after SARS-COV2 vaccine. Male, 76 years old, with a history of hepatic cirrhosis secondary to primary biliary cholangitis (PBC), compensated, treated with ursodeoxycholic acid and obeticholic acid. The patient received the third dose of the SARS-CoV2 vaccine (BioNTech/Pfizer) in December 2021. In subsequent analytical control, the patient presented altered liver test, with elevation of ALT and AST. Ultrasound was performed, without alterations, and viral causes were ruled out. IgG elevation and positive antinuclear antibodies were observed. A liver biopsy was performed, with findings of intense interface and lobular hepatitis and areas of centrilobular necrosis. The inflammation was predominantly lymphoplasmacytic. The patient was diagnosed with AIH and initiated therapy with steroids and azathioprine, currently with an adequate response. AIH is an immune-mediated disease of uncertain etiology. Cases of AIH with SARS-CoV2 vaccination as a possible trigger have recently been published, with characteristics similar to ours. Some of them had a history of autoimmune pathology, such as this case (PBC). Therefore, it is suggested that vaccination can induce the development of autoimmune pathology in patients at risk. Our reported case reinforces the hypothesis of an association between AIH and the SARS-CoV2 vaccine.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified 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 analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

Autoimmune hepatitis triggered by SARS-CoV-2 vaccination.

The development of autoimmune diseases has been reported after SARS-CoV-2 infection. Vaccination against SARS-CoV-2 could also trigger auto-immunity, as it has been described with other vaccines. An aberrant immune response induced by molecular mimicry and bystander activation, especially in predisposed individuals, is a potential mechanism. We report the case of a 76-year-old woman with Hashimoto thyroiditis and prior COVID-19 infection who developed severe autoimmune hepatitis (with typical features including strongly positive anti-smooth muscle antibody and markedly elevated immunoglobulins G, as well as typical histological findings) following SARS-CoV-2 vaccination (mRNA-1273 SARS-CoV-2 vaccine, Moderna®). The link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated. Although a causality relationship cannot be proven, caution may be warranted when vaccinating individuals with known autoimmune diseases.

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

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.

Autoimmune hepatitis triggered by COVID-19.

We present the case of a 60-year-old female with no drug allergies or toxic habits, with hypothyroidism, and receiving treatment with levothyroxine. She was admitted in February 2021 and presented with choluria of 72 hours duration; there were no abdominal or respiratory clinical symptoms, and no related fever. Medical examination findings included mucocutaneous jaundice and a recorded oxygen saturation of 97 % in ambient air. There was a notable pattern of cytolysis compatible with acute hepatitis, and no history hepatotoxic drugs. Screening was performed for acute hepatitis in addition to serology testing, determination of autoantibodies and immunoglobulins, a PCR test for COVID, and a radiologic study.