Hospital for Sick Children, Toronto, Ontario, Canada.
Hospital for Sick Children, Toronto, Ontario, Canada.
J Pediatr. 2018 Mar;194:128-135.e1. doi: 10.1016/j.jpeds.2017.10.071. Epub 2017 Dec 21.
To evaluate a large anti-tumor necrosis factor (TNF)-treated pediatric inflammatory bowel disease cohort for drug-induced liver injury (DILI) following presentation of an index case with suspected DILI with autoimmune features after infliximab exposure. To characterize the incidence, natural history, and risk factors for liver enzyme elevation with anti-TNF use.
We reviewed the index case and performed a retrospective cohort study of 659 children receiving anti-TNF therapy between 2000 and 2015 at a tertiary pediatric inflammatory bowel disease center. Patients with alanine aminotransferase (ALT) ≥×2 the upper limit of normal were included. The incidence, evolution, and risk factors for liver injury were examined with univariate and multivariable proportional hazards regression. Causality was assessed using the Roussel-Uclaf Causality Assessment Method.
The index case, a teenage girl with Crohn's disease, developed elevated liver enzymes and features of autoimmune hepatitis on liver biopsy 23 weeks after starting infliximab. The injury resolved entirely within 4 months of withdrawing infliximab without additional therapy. Overall, 7.7% of our cohort developed new ALT elevations while on anti-TNF. Most ALT elevations were mild and transient and attributable to alternate etiologies. No additional clear cases of autoimmune hepatitis were identified.
Transient liver enzyme abnormalities are relatively common among anti-TNF-treated children. Anti-TNF-related DILI with autoimmune features is rare but must be recognized so that therapy can be stopped.
评估一个大型抗 TNF 治疗小儿炎症性肠病队列，该队列中一名患儿在接受英夫利昔单抗治疗后出现疑似具有自身免疫特征的 DILI，该患儿为索引病例。目的在于评估抗 TNF 治疗后发生药物性肝损伤（DILI）的情况，以明确其发生率、自然史和肝酶升高的风险因素。
我们对索引病例进行了研究，并对 2000 年至 2015 年在一家三级儿科炎症性肠病中心接受抗 TNF 治疗的 659 例儿童进行了回顾性队列研究。纳入丙氨酸氨基转移酶（ALT）≥2 倍正常值上限的患者。使用单变量和多变量比例风险回归分析评估肝损伤的发生率、演变和风险因素。使用 Roussel-Uclaf 因果关系评估方法评估因果关系。
索引病例是一名患有克罗恩病的少女，在开始使用英夫利昔单抗 23 周后出现肝酶升高和自身免疫性肝炎的特征。在停用英夫利昔单抗后 4 个月内，损伤完全消退，无需额外治疗。总体而言，7.7%的患儿在接受抗 TNF 治疗时出现新的 ALT 升高。大多数 ALT 升高是轻度和短暂的，归因于其他病因。未发现其他明确的自身免疫性肝炎病例。
在接受抗 TNF 治疗的儿童中，肝酶异常是相对常见的。具有自身免疫特征的抗 TNF 相关 DILI 罕见，但必须加以识别，以便停止治疗。
