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
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)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
January 12,
2023
Received in revised form:
December 14,
2022
Received:
July 18,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
