Acute liver injury with autoimmune features following SARS-CoV-2 vaccination in an ERN/IAIHG cohort: autoimmune hepatitis versus drug-induced autoimmune-like hepatitis

Abstract

Background and aims: It is unclear whether the reported rare cases of acute liver injury with autoimmune features after COVID-19 vaccination represent autoimmune hepatitis (AIH) triggered by the vaccines, requiring long-term immunosuppression, or if the liver injury is self-limiting, as observed in drug-induced autoimmune-like hepatitis (DI-ALH). We report follow-up data of our international cohort of well characterized patients aiming at understanding if the disease course is self-limiting or immunosuppression dependent. Method: Members of the International AIH Group and of the European Reference Network on Hepatological Diseases who had contributed cases to our original cohort were asked to provide followup data of all their patients at 6 and 12 months after the hepatitis diagnosis and at last follow-up. Results: 62 patients were included, median age was 56 years, 35 (56%) female. Median follow-up was 17 months. Fifty-eight patients (94%) were treated with steroids, with or without azathioprine or mycophenolate mofetil. Four patients (6%) died of non-liver related causes. Transaminase levels normalization was achieved by 74%, 85% and 88% of patients at 6 months, 12 months and at last follow-up (median 17 months). Twenty-two patients (35%) had a phenotype and clinical course similar to DI-ALH, characterized by ALT normalization with (n = 18) or without (n = 4) a short (<9 months) immunosuppressive treatment, and no relapse after treatment discontinuation; 18 patients (30%) had a course similar to AIH, characterized by relapse after immunosuppression discontinuation (n = 10), still abnormal ALT levels after 6 months (n = 5) or 12 months (n = 3) of treatment duration; for 22 patients (35%) it was not possible, based on the available data, to assign them to one of the previous groups. Risk factors for a classical AIH course were: positive antismooth muscle antibodies at diagnosis (p = 0.04), advanced liver fibrosis (p = 0.03), and more severe interface hepatitis (p = 0.02). Conclusion: Most patients with acute liver injury and autoimmune features after COVID-19 vaccination appear to have DI-ALH, but a sizable subgroup with a more severe phenotype requires long-term immunosuppression, akin to classical AIH.