Steg Saban Or, Vandriel Shannon M, Fatima Syeda Aiman, Bourdon Celine, Mundh Amrita, Ng Vicky L, Ling Simon C, Bandsma Robert H J, Kamath Binita M
Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Hepatol Commun. 2025 Feb 3;9(2). doi: 10.1097/HC9.0000000000000624. eCollection 2025 Feb 1.
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.
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.
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.
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.
自身免疫性肝炎（AIH）患儿的标准治疗方案包括每日使用泼尼松1 - 2毫克/千克进行诱导治疗，并逐渐减少剂量。我们旨在验证接受标准治疗的AIH患儿生长轨迹发生改变这一假设。
1997年至2023年在病童医院被诊断为AIH的患儿进行了连续生长测量。混合效应模型评估时间和每日类固醇暴露对z评分的影响。采用Kaplan - Meier生存方法估计新发生长障碍的累积发生率。构建时间依赖性Cox比例风险模型以确定生长障碍的预测因素。
纳入61名儿童（66%为女性，诊断时中位年龄11.5岁）。体重指数z评分急剧上升，身高别体重z评分显著下降且未恢复到基线水平。每1毫克/千克/天的泼尼松暴露在最初6个月使体重指数z评分增加0.27（[95%置信区间：0.11, 0.42]，p = 0.001），并使身高别体重z评分降低 - 0.02（[95%置信区间： - 0.03, - 0.01]，p = 0.005）。与青春期诊断的患儿相比，青春期前诊断的患儿出现体重过度增加（72.2%对49.3%；对数秩检验p < 0.01）和肥胖（63%对31.5%；对数秩检验p < 0.01）的发生率更高。在Cox比例风险模型中，诊断时年龄小以及诊断后6个月每日泼尼松剂量>10毫克是线性生长延迟的预测因素。
本研究表明，接受标准治疗的AIH患儿生长轨迹发生改变，出现长期体重过度增加、肥胖和线性生长延迟。诊断时年龄小以及6个月时每日泼尼松剂量>10毫克是线性生长延迟的预测因素。这些数据表明需要在类固醇给药和潜在的非类固醇替代方案方面重新评估儿童AIH的标准治疗算法。
