ABSTRACT
Background & Aims Liver injury with autoimmune features after vaccination against Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of patients with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Approach & Results Patients without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine and available liver biopsy are included. Fifty-nine patients were recruited;35 females;median age 54 years;they were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Liver histology showed predominantly lobular hepatitis in 45 (76%) cases, predominantly portal hepatitis in 10 (17%), and other patterns in four (7%);seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in 8 (26%), anti-liver kidney microsomal in 4 (13%), anti-mitochondrial antibody in 4 (13%). Ninety-one percent were treated with steroids, ± azathioprine. Serum transaminase levels improved in all cases, and were normal in 24/58 (41%) after three months, and in 30/46 (65%) after six months. One patient required liver transplantation. Re-exposure to SARS-CoV-2 vaccines of 15 patients resulted in three relapses. Conclusion Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcome of this condition. Lay summary Cases of liver injury after vaccination against Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of patients with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition.