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 individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals 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 were 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. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases;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 eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. 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 outcomes of this condition. Impact and implications: 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 individuals 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. © 2022 The Author(s)
ABSTRACT
Background: Several studies have been published on a rare side effect of severe venous thrombosis at unusual sites and thrombocytopenia after vaccination against SARS-CoV- 2, referred to as vaccine-induced immune thrombocytopenia and thrombosis (VITT). Aim(s): To identify new cases of acute splanchnic vein thrombosis (SVT) or Budd-Chiari Syndrome (BCS) who presented following SARS-CoV- 2 vaccination in the Vascular Liver Disease Group (VALDIG) network, and to evaluate the incidence of VITT. Method(s): We conducted a prospective international cohort study between May 1st, 2021 and January 10th, 2022, on consecutive patients with acute SVT or BCS who presented within 6 weeks following any type or dose of SARS-CoV- 2 vaccination. Anonymous data were collected including baseline characteristics, risk factors, treatment and survival. Cases were identified as definite VITT, probable VITT or possible VITT or unlikely VITT as defined by Pavord et al (NEJM 2021). Result(s): 25 patients with acute (N = 24) or recurrent (N = 1) SVT or BCS were collected from 14 centers in 4 countries (after ChAdOx1 nCoV-19 N = 11, BNT162b2 N = 9, Ad26.COV2.S N = 1, mRNA-1273 N = 1). Median time after vaccination to symptoms was 10 days (2-40). Median age was 52.5 years (21-66), 52% were female. Three patients (12%) fulfilled criteria for definite VITT, 6 (24%) for probable VITT, 2 (8%) for possible VITT, 14 (56%) for unlikely VITT. Thrombosis was located in the portal vein (N = 20), hepatic vein(s) (N = 9), mesenteric vein (N = 18) or splenic vein (N = 9). Concomitant extra-abdominal thrombosis was seen in 5 patients (20%). Patients were treated with LMWH (60%), DOACs (24%) or VKA (40%). Six (2/3 with definite VITT) received IVIG. Thrombophilia was found in 5 patients and 3 had a myeloproliferative neoplasm. Conclusion(s): 25 cases of acute SVT or BCS following SARS-CoV- 2 vaccination were identified. Although definite VITT was rare (12%), no underlying disorder was identified in the majority of patients, contrary to 'typical' cases of SVT and BCS.