Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Am J Gastroenterol. 2010 Jul;105(7):1620-6. doi: 10.1038/ajg.2010.21. Epub 2010 Feb 16.
We aimed to characterize the spectrum of liver enzyme test (LET) abnormalities that occur while using methotrexate for inflammatory bowel disease (IBD).
A retrospective review was undertaken of subjects using methotrexate for IBD at a single center. The clinical and epidemiological parameters, and hepatotoxicity risk factors, were recorded. Subjects were excluded if cumulative methotrexate doses could not be ascertained, if they had a diagnosis of rheumatoid arthritis or psoriasis, or if baseline and follow-up LETs were not available. Also noted were the cumulative methotrexate dose during the peak LET increase, severity of LET increase, and whether normalization occurred.
Eighty-seven subjects were included (Crohn's disease, n=67; UC, n=17; indeterminate colitis n=3). The mean therapy duration was 81 weeks (3- to 364-week range), and the cumulative average dose was 1,813 mg (25-8,255-mg range). Thirty-seven (43%) subjects received a cumulative dose >1,500 mg. Sixty-seven (77%) had normal LETs, and in 51 (76%) LETs remained normal throughout methotrexate therapy. In the 16 (24%) who developed LET abnormalities, seven (44%) had underlying risk factor(s) for liver disease. Normalization (without dose reduction) occurred in 14 (88%) while continuing methotrexate. Of 20 subjects with abnormal LETs at baseline, nine (45%) subsequently normalized while continuing methotrexate, whereas nine (45%) worsened. Seventeen liver biopsies were performed in 11 and were classified as Roenigk's grade I in 15 (88%) subjects. Roenigk IIIb or IV was not seen.
Methotrexate is commonly associated with LET abnormalities, but these frequently normalize while still on therapy, and in only 5% will drug discontinuation be necessary. Liver biopsies rarely have substantive abnormalities.
本研究旨在描述在使用甲氨蝶呤治疗炎症性肠病（IBD）时发生的肝酶试验（LET）异常谱。
对单中心使用甲氨蝶呤治疗 IBD 的患者进行回顾性研究。记录临床和流行病学参数以及肝毒性危险因素。如果无法确定累积甲氨蝶呤剂量、如果患有类风湿关节炎或银屑病、或如果基线和随访 LET 不可用，则排除患者。还记录了在 LET 升高峰值期间的累积甲氨蝶呤剂量、LET 升高的严重程度以及是否正常化。
共纳入 87 例患者（克罗恩病，n=67；溃疡性结肠炎，n=17；未确定结肠炎，n=3）。平均治疗时间为 81 周（3-364 周），累积平均剂量为 1813mg（25-8255mg）。37 例（43%）患者累积剂量>1500mg。67 例（77%）患者 LET 正常，51 例（76%）患者在整个甲氨蝶呤治疗期间 LET 正常。在 16 例（24%）发生 LET 异常的患者中，7 例（44%）存在肝脏疾病的潜在危险因素。在继续使用甲氨蝶呤的情况下，14 例（88%）患者实现了正常化（无需减少剂量）。在基线时有异常 LET 的 20 例患者中，9 例（45%）在继续使用甲氨蝶呤的情况下随后恢复正常，而 9 例（45%）则恶化。11 例患者进行了 17 次肝活检，其中 15 例（88%）患者被分类为 Roenigk Ⅰ级。未见 Roenigk Ⅲb 或 IV 级。
甲氨蝶呤常与 LET 异常相关，但这些异常通常在治疗期间仍会正常化，只有 5%的患者需要停药。肝活检很少有实质性异常。
