Section of Gastroenterology and Hepatology at Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Inflamm Bowel Dis. 2012 Feb;18(2):359-67. doi: 10.1002/ibd.21820. Epub 2011 Jul 12.
Crohn's disease and ulcerative colitis are chronic debilitating diseases for which there are multiple treatment options. There are limited data on methotrexate's efficacy and safety profile. Our aim was to estimate the hepatotoxicity associated with its use in inflammatory bowel diseases (IBDs).
We systematically searched the Medline, Cochrane Library, Web of Science, and EMBASE databases and manually examined references in selected articles for trials that used methotrexate as a treatment for IBDs. Thirteen trials that fulfilled the inclusion and exclusion criteria were included in the meta-analysis. Information on trial and patient characteristics, use of methotrexate as well as other treatments or placebo, and levels of hepatic aminotransferase enzymes were abstracted by two independent investigators using a standardized form. A random effects model was used to pool the incidence rates of reported abnormalities in hepatic aminotransferases.
The pooled incidence rate of abnormal hepatic aminotransferase levels (defined as up to a 2-fold increase over the upper limit of the normal range) in patients treated with methotrexate for IBD was 1.4 per 100 person-months, while the rate of hepatotoxicity (defined as greater than a 2-fold over the upper limit of the normal range) was 0.9 per 100 person-months. The rate of withdrawal from treatment due to these abnormalities was 0.8 per 100 person-months.
The incidence of methotrexate-related hepatotoxicity as measured by elevation in transaminases and drug withdrawal secondary to elevated transaminases is relatively low.
克罗恩病和溃疡性结肠炎是两种慢性衰弱性疾病，有多种治疗选择。关于甲氨蝶呤的疗效和安全性数据有限。我们的目的是评估其在炎症性肠病（IBD）中的肝毒性。
我们系统地检索了 Medline、Cochrane 图书馆、Web of Science 和 EMBASE 数据库，并手动检查了选定文章中的参考文献，以寻找使用甲氨蝶呤治疗 IBD 的试验。符合纳入和排除标准的 13 项试验被纳入荟萃分析。两名独立研究者使用标准化表格摘录了试验和患者特征、甲氨蝶呤的使用以及其他治疗或安慰剂、肝转氨酶水平的信息。使用随机效应模型对报告的肝转氨酶异常发生率进行合并。
用甲氨蝶呤治疗 IBD 的患者中，异常肝转氨酶水平（定义为超过正常范围上限的 2 倍）的合并发生率为每 100 人月 1.4 例，而肝毒性（定义为超过正常范围上限的 2 倍）的发生率为每 100 人月 0.9 例。由于这些异常而停止治疗的发生率为每 100 人月 0.8 例。
用转氨酶升高和因转氨酶升高而停药来衡量的甲氨蝶呤相关肝毒性的发生率相对较低。
