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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

  • Donald Malino
  • , Greta Codoni
  • , Theresa Kirchner
  • , Bastian Engel
  • , Alejandra Maria Villamil
  • , Cumali Efe
  • , Albert Friedrich Stattermayer
  • , Jan Philipp Weltzsch
  • , Marcial Sebode
  • , Christine Bernsmeier
  • , Ana Lleo
  • , Tom J. G. Gevers
  • , Limas Kupcinskas
  • , Agustin Castiella
  • , Jose Pinazo
  • , Eleonora De Martin
  • , Ingrid Bobis
  • , Thomas Damgaard Sandahl
  • , Federica Pedica
  • , Federica Invernizzi
  • Paolo Del Poggio, Tony Bruns, Mirjam Kolev, Nasser Semmo, Fernando Bessone, Baptiste Giguet, Guido Poggi, Masayuki Ueno, Helena Jang, Gulsum Ozlem Elpek, Nese Karadag Soylu, Andreas Cerny, Heiner Wedemeyer, Matthias S. Matter, Sarp Uzun, Gonzalo Matilla-Cabello, Diego Vergani, Giorgina Mieli-Vergani, M. Isabel Lucena, Raul J. Andrade, Yoh Zen, Richard Taubert, Benedetta Terziroli Beretta-Piccoli*
*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)615-624
Number of pages10
JournalEuropean Journal of Gastroenterology & Hepatology
Volume38
Issue number5
DOIs
Publication statusPublished - 1 May 2026

Keywords

  • autoimmune hepatitis
  • COVID-19 vaccines
  • follow-up
  • severe acute respiratory syndrome coronavirus 2 vaccine-associated liver injury
  • vaccine-induced hepatitis
  • DIAGNOSIS
  • CRITERIA

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