Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
Department of Pediatrics, Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland.
J Pediatr Gastroenterol Nutr. 2024 Sep;79(3):583-591. doi: 10.1002/jpn3.12300. Epub 2024 Jul 1.
Biological treatments (BTs) are essential in managing pediatric inflammatory bowel diseases (PIBDs). Elevated liver enzymes sometimes succeed BT, yet elucidating studies are scarce. We addressed liver biochemistry after introducing BT and searched for their determinants.
We identified PIBD patients receiving infliximab, adalimumab, vedolizumab, or ustekinumab at the Children's Hospital, University of Helsinki, Finland, in 2000-2023, and followed their alanine transaminase (ALT) and γ-glutamyl transpeptidase (GT) levels for 24 months. ALT was categorized based on the age- and sex-specific upper limit of normal. We disregarded 46 patients with underlying primary sclerosing cholangitis with/without autoimmune hepatitis (AIH), pretreatment AIH diagnosis, and elevated liver enzymes at the beginning of BT from the analyses.
Of 618 BT episodes in 403 patients, 22.2% exhibited increased ALT or GT (ALT in 117, GT in 4, and both ALT/GT in 16 episodes). Of all ALT elevations (n = 133), 41.4% occurred within the first 3 months. ALT elevation was more common after infliximab (representing 59.5% of BTs) than other BTs (25.9% vs. 14.2%, adjusted odds ratio [OR]: 2.41, 95% confidence interval [CI]: 1.23-4.72). AIH followed 1.5% (n = 9) of BT episodes. Ninety-five percent of ALT elevations resolved within 6 months. Antibiotic exposure (particularly to metronidazole) was associated with ALT elevation in general (adjusted OR: 5.76, 95% CI: 2.40-13.9) and short disease duration before starting BT with notable ALT elevation (adjusted OR: 1.10, 95% CI: 1.01-1.22).
Benign ALT elevation is common within 3 months after starting BT (especially infliximab) and scarcely led to cessation of the treatment. AIH is a rare finding during the first year of BT.
生物制剂（BTs）对于治疗小儿炎症性肠病（PIBDs）至关重要。有时升高的肝酶会影响 BT 的效果，但相关研究仍较少。本研究旨在介绍 BT 后检测肝生化，并探讨其决定因素。
我们在芬兰赫尔辛基大学儿童医院识别了 2000 年至 2023 年接受英夫利昔单抗、阿达木单抗、维得利珠单抗或乌司奴单抗治疗的 PIBD 患者，并对其 24 个月的丙氨酸氨基转移酶（ALT）和γ-谷氨酰转肽酶（GT）水平进行了随访。ALT 基于年龄和性别特异性正常上限进行分类。我们从分析中排除了 46 例存在原发性硬化性胆管炎和/或自身免疫性肝炎（AIH）、预处理 AIH 诊断以及 BT 开始时肝酶升高的患者。
在 403 名患者的 618 次 BT 中，22.2%（117 例 ALT 升高，4 例 GT 升高，16 例同时升高）出现 ALT 或 GT 升高。所有 ALT 升高（n=133）中，41.4%发生在治疗开始后 3 个月内。英夫利昔单抗后 ALT 升高更为常见（占 BT 的 59.5%），而其他 BT 中则较少见（25.9% vs. 14.2%，调整后的比值比[OR]：2.41，95%置信区间[CI]：1.23-4.72）。BT 后有 1.5%（n=9）发生 AIH。95%的 ALT 升高在 6 个月内恢复正常。一般而言，抗生素暴露（尤其是甲硝唑）与 ALT 升高相关（调整后的 OR：5.76，95%CI：2.40-13.9），BT 前疾病持续时间较短且明显 ALT 升高（调整后的 OR：1.10，95%CI：1.01-1.22）。
BT 开始后 3 个月内，丙氨酸氨基转移酶（ALT）升高较为常见（尤其是英夫利昔单抗），但很少导致治疗中断。BT 治疗第一年发现 AIH 较为罕见。
