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Updated: May 29, 2025

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms
Published on: May 29, 2020
Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth
Or Steg Saban1, Shannon M Vandriel1, Syeda Aiman Fatima1
1Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Insights
Standard treatment for autoimmune hepatitis (AIH) in children can lead to significant weight gain and growth delays. Early diagnosis and lower prednisone doses are crucial for better growth outcomes in pediatric AIH patients.
Area of Science:
- Pediatric Gastroenterology
- Hepatology
- Endocrinology
Background:
- Autoimmune hepatitis (AIH) in children is typically managed with prednisone induction.
- Concerns exist regarding the impact of standard AIH treatment on pediatric growth trajectories.
Purpose of the Study:
- To investigate the effects of standard AIH therapy on growth patterns in children.
- To identify predictors of altered growth and identify potential areas for treatment modification.
Main Methods:
- Retrospective analysis of growth data from 61 children diagnosed with AIH between 1997 and 2023.
- Mixed-effects models and Cox proportional-hazards models were used to assess growth z-scores and predict growth impairments.
Main Results:
- AIH treatment led to increased BMI z-scores and decreased height z-scores.
- Higher prednisone doses correlated with greater BMI gain and reduced height.
- Children diagnosed before puberty showed higher rates of excessive weight gain and obesity.
Conclusions:
- Standard AIH therapy in children is associated with adverse growth outcomes, including obesity and linear growth delay.
- Younger age at diagnosis and higher prednisone doses at 6 months predict linear growth delay.
- Current treatment protocols for pediatric AIH may require re-evaluation regarding steroid management and non-steroid alternatives.
Background:
Standard-of-care therapy in children with autoimmune hepatitis (AIH) includes induction with prednisone 1-2 mg/kg daily with gradual weaning of the dose. We aimed to test the hypothesis that children with AIH receiving standard-of-care treatment have altered growth trajectories.
Methods:
Children diagnosed with AIH between 1997 and 2023 at SickKids had serial growth measurements. Mixed effect models assessed the impact of time and daily steroid exposure on z-scores. Kaplan-Meier survival methods were used to estimate the cumulative incidence of new-onset growth impairments. A time-dependent Cox proportional hazards model was constructed to determine predictors for growth impairments.
Results:
Sixty-one children (66% females, median age at diagnosis 11.5 y) were included. BMIz showed a sharp increase, and HAZ declined significantly without returning to baseline. Each 1 mg/kg/d prednisone exposure increased BMIz gain in the first 6 months by 0.27 ([95% CI: 0.11, 0.42], p = 0.001), and decreased HAZ by -0.02 ([95% CI: -0.03, -0.01], p = 0.005). Children diagnosed before puberty exhibited a higher occurrence of excessive weight gain (72.2% vs. 49.3%; log-rank p < 0.01) and obesity (63% vs. 31.5%; log-rank p < 0.01) compared to those diagnosed during puberty. In a Cox proportional-hazards model, young age at diagnosis and daily prednisone dose >10 mg 6 months after diagnosis were predictors for linear growth delay.
Conclusions:
This study demonstrates that children with AIH receiving standard-of-care therapy demonstrate altered growth trajectories, long-term excess weight gain, obesity, and linear growth delay. Young age at diagnosis and >10 mg of daily prednisone at 6 months are predictors for linear growth delay. These data indicate the need to re-evaluate standard treatment algorithms for pediatric AIH in terms of steroid dosing and potential nonsteroid alternatives.
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