Clinical course and prognostic risk factors of SARS-CoV-2 vaccine-related hepatitis: differentiating severe acute respiratory syndrome coronavirus 2 vaccine-associated liver injury from autoimmune hepatitis

Background and aim Reported cases of acute liver injury with autoimmune features post-COVID-19 vaccination raise questions about whether this represents vaccine-triggered autoimmune hepatitis (AIH) or self-limiting drug-induced autoimmune-like hepatitis (DI-ALH). We report follow-up data to determine if the disease course is self-limiting or immunosuppression-dependent. Methods Members of the International AIH Group and the European Reference Network on Hepatological Diseases who contributed cases to our original cohort provide follow-up data at 6 months, 12 months, and at last follow-up. Results Sixty-two patients (median age 56 years, 35 female) were included (median follow-up: 22.8 months). Fifty-eight (93%) received steroids +/- azathioprine/mycophenolate. Four died of non-liver-related causes. Transaminases normalization rates were 71, 92, and 90% at 6 months, 12 months, and last follow-up, respectively. Twenty-four had a DI-ALH-like course, with ALT normalization and no relapse with or without (n = 4) a short (<9 months) immunosuppressive treatment. Nineteen had an AIH-like course, with relapse after discontinuation (n = 11) or persistent ALT elevation despite treatment (n = 8). Nineteen were unclassified. Risk factors for AIH-like progression included a higher revised AIH score, advanced fibrosis, and severe interface hepatitis. Conclusion Most cases resemble DI-ALH, which we propose naming severe acute respiratory syndrome coronavirus 2 vaccine-associated liver injury, but a significant subset requires long-term immunosuppression, resembling classical AIH.