Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delay

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...

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Main Authors: Or Steg Saban, Shannon M. Vandriel, Syeda Aiman Fatima, Celine Bourdon, Amrita Mundh, Vicky L. Ng, Simon C. Ling, Robert H.J. Bandsma, Binita M. Kamath
Format: Article
Language:English
Published: Wolters Kluwer Health/LWW 2025-02-01
Series:Hepatology Communications
Online Access:http://journals.lww.com/10.1097/HC9.0000000000000624
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author Or Steg Saban
Shannon M. Vandriel
Syeda Aiman Fatima
Celine Bourdon
Amrita Mundh
Vicky L. Ng
Simon C. Ling
Robert H.J. Bandsma
Binita M. Kamath
author_facet Or Steg Saban
Shannon M. Vandriel
Syeda Aiman Fatima
Celine Bourdon
Amrita Mundh
Vicky L. Ng
Simon C. Ling
Robert H.J. Bandsma
Binita M. Kamath
author_sort Or Steg Saban
collection DOAJ
description 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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spelling doaj-art-09bc5a40ca184f428ac9015ea290208e2025-02-05T02:10:59ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2025-02-019210.1097/HC9.0000000000000624HC90000000000000624Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delayOr Steg Saban0Shannon M. Vandriel1Syeda Aiman Fatima2Celine Bourdon3Amrita Mundh4Vicky L. Ng5Simon C. Ling6Robert H.J. Bandsma7Binita M. Kamath8 1 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada 1 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada 1 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada 2 Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada 1 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada 1 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada 1 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada 1 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada 1 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, CanadaBackground:. 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.http://journals.lww.com/10.1097/HC9.0000000000000624
spellingShingle Or Steg Saban
Shannon M. Vandriel
Syeda Aiman Fatima
Celine Bourdon
Amrita Mundh
Vicky L. Ng
Simon C. Ling
Robert H.J. Bandsma
Binita M. Kamath
Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delay
Hepatology Communications
title Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delay
title_full Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delay
title_fullStr Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delay
title_full_unstemmed Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delay
title_short Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delay
title_sort children with autoimmune hepatitis receiving standard of care therapy demonstrate long term obesity and linear growth delay
url http://journals.lww.com/10.1097/HC9.0000000000000624
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