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Long-term outcomes of patients with type 1 or 2 autoimmune hepatitis presenting in childhood

  • Giuseppe Maggiore
    Correspondence
    Corresponding author: Epatogastroenterologia, Riabilitazione Nutrizionale, Endoscopia Digestiva e Clinica Del Trapianto di Fegato, Ospedale Pediatrico Bambino Gesù, Piazza Sant’Onofrio 4, 00165, Roma, Italy. +39 06 6859 4973
    Affiliations
    Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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  • Olivier Bernard
    Affiliations
    Paediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Inflammatory Biliary Diseases and Autoimmune Hepatitis, FILFOIE, ERN RARE LIVER, Bicêtre Hospital, APHP, University Paris-Saclay, Le Kremlin-Bicêtre, France
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  • Antonella Mosca
    Affiliations
    Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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  • Eric Ballot
    Affiliations
    Laboratory of Autoimmunity, Department of Immunology, St Antoine Hospital, APHP, Sorbonne University, Paris, France
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  • Catherine Johanet
    Affiliations
    Laboratory of Autoimmunity, Department of Immunology, St Antoine Hospital, APHP, Sorbonne University, Paris, France
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  • Emmanuel Jacquemin
    Affiliations
    Paediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Inflammatory Biliary Diseases and Autoimmune Hepatitis, FILFOIE, ERN RARE LIVER, Bicêtre Hospital, APHP, University Paris-Saclay, Le Kremlin-Bicêtre, France

    Inserm U1193, Hepatinov, University Paris-Saclay, Orsay, France
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Published:January 24, 2023DOI:https://doi.org/10.1016/j.jhep.2023.01.013

      Highlights

      • No differences in outcome between type 1 and type 2 autoimmune hepatitis in children.
      • 19% possibility of ≥ 4-year treatment-free survival throughout childhood and early adulthood.
      • 45%, 4 to 22-year relapse-free children, after withdrawal, based on lasting normal transaminase only, without histology.
      • 81% and 61% 30-year probabilities of overall survival and survival with native liver, respectively.
      • Lasting abnormal prothrombin detects patients who will require liver transplantation in adolescence or early adulthood.

      Abstract

      Background & Aims

      In children with autoimmune hepatitis, issues include the particularities of type 2 hepatitis regarding outcome, the possibility of and criteria for attempting withdrawal of treatment and the long-term outcome. We report our experience on these issues.

      Methods

      From 1973 to 2002, 117 children with type 1 (n=65) or type 2 (n=52) hepatitis, excluding fulminant hepatitis, were treated, primarily with prednisone and azathioprine. Median follow-up was 20 years in survivors.

      Results

      Normalization of transaminase and prothrombin ratio were observed in 93% and 84% of children, respectively; sustained remission after treatment withdrawal was recorded in 24% of the entire population with a median follow-up of 7 years. Based on lasting normal aminotransferase only and without histology, sustained treatment-free remission was obtained in 11 of 24 children with follow-ups of 4-22 years. Gastrointestinal bleeding from varices and the emergence of extrahepatic autoimmune disorders occurred in 10 and 22 patients, respectively. Liver transplantation was performed in 23 patients at a median age of 21 years. The 30-year probabilities of overall survival and native liver survival were 81% and 61%. No differences were observed between types 1 and 2 hepatitis for any of the component parts of outcome. In the multivariate analysis, a persistent abnormal prothrombin ratio was combined with worse probabilities of overall and native liver survivals.

      Conclusions

      In terms of liver outcome, type 2 hepatitis is not different from type 1. Withdrawal of treatment is possible without prior liver histology. A persistent abnormal prothrombin ratio identifies patients who will require liver transplantation in adolescence or early adulthood.

      Impact and implications

      In children with autoimmune hepatitis, there are conflicting reports on the differences between type 1 and type 2 hepatitis regarding outcome, and on the possibility of treatment withdrawal, before which liver histology is required; data concerning >10-year overall and native liver survivals are limited. In this study we found no differences between types 1 and 2 hepatitis; a durable treatment-free state was achieved in 19% of all patients throughout childhood and early adulthood, and in 45% of children for whom treatment withdrawal was attempted without prior liver histology; prothrombin was found to be predictive of 30-year overall and native liver survivals. The results allow a softer approach to treatment withdrawal in children, avoiding the risks of a liver biopsy, and they provide a tool to help anticipate the need for liver transplantation before complications occur.

      Graphical abstract

      Keywords

      Abbreviations:

      AIH (autoimmune hepatitis), ALT (alanine aminotransferase), ANA (anti-nuclear antibodies), SMA (anti-smooth muscle antibodies), ULN (upper limit of normal), anti-LKM1 (anti-liver-kidney microsome type 1 antibodies), anti-LC1 (anti-liver cytosol antibodies), IAIHG (International Autoimmune Hepatitis Group)
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