1Division of Gastroenterology, Hepatology, and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; 2Neonatal Intensive Care Unit, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Toronto, ON, Canada; and 4Division of Rheumatology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Inflamm Bowel Dis. 2014 Jan;20(1):47-59. doi: 10.1097/01.MIB.0000436953.88522.3e.
Methotrexate (MTX) is an immunomodulator used in pediatric inflammatory bowel disease (IBD) maintenance regimens. However, MTX use is associated with liver toxicity. We aimed to systematically review and meta-analyze the incidence of hepatotoxicity with MTX use among children with IBD.
We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases from 1946 to April 2013 for cohort studies and collected information about the study design, IBD treatment results, and hepatotoxicity. Pooled proportions of toxicity with 95% confidence interval (CI) were estimated using a random-effects model.
Twelve high-quality studies were included in this review. Fifty-seven of 457 patients treated with MTX developed varied degrees of abnormal liver biochemistry. The pooled proportion of patients with abnormal liver biochemistry was 10.2% (95% CI 5.4%-18.5%) across all studies included in the meta-analysis. Due to hepatotoxicity, dose reductions were required in 6.4% (95% CI 4.3%-9.5%), whereas 4.5% (95% CI 2.8%-7.2%) of patients required discontinuation.
Hepatotoxicity after the use of MTX among IBD patients was a relatively common event. Monitoring for hepatotoxicity is strongly recommended, as discontinuation of MTX may be necessary in a significant proportion of children.
甲氨蝶呤（MTX）是一种免疫调节剂，用于儿科炎症性肠病（IBD）的维持治疗方案。然而，MTX 的使用与肝毒性有关。我们旨在系统地回顾和荟萃分析 MTX 在儿童 IBD 中的使用与肝毒性的关系。
我们检索了 MEDLINE、EMBASE、Web of Science 和 Cochrane 对照试验中心注册数据库，从 1946 年至 2013 年 4 月，以收集关于研究设计、IBD 治疗结果和肝毒性的信息。使用随机效应模型估计毒性的合并比例及其 95%置信区间（CI）。
本综述共纳入了 12 项高质量的研究。在接受 MTX 治疗的 457 例患者中，有 57 例出现不同程度的异常肝功能。荟萃分析中纳入的所有研究的患者出现异常肝功能的合并比例为 10.2%（95%CI 5.4%-18.5%）。由于肝毒性，需要减少剂量的比例为 6.4%（95%CI 4.3%-9.5%），而需要停药的比例为 4.5%（95%CI 2.8%-7.2%）。
IBD 患者使用 MTX 后发生肝毒性是一个相对常见的事件。强烈建议监测肝毒性，因为在相当一部分儿童中可能需要停止 MTX 的使用。
