Te H S, Schiano T D, Kuan S F, Hanauer S B, Conjeevaram H S, Baker A L
Department of Medicine, University of Chicago Hospitals, Illinois 60637, USA.
Am J Gastroenterol. 2000 Nov;95(11):3150-6. doi: 10.1111/j.1572-0241.2000.03287.x.
Methotrexate is currently used as a treatment for refractory inflammatory bowel disease. This study sought to evaluate the hepatic effects of long-term methotrexate therapy in patients with inflammatory bowel disease and to determine whether the established guidelines for monitoring methotrexate-related hepatotoxicity with surveillance liver biopsy in patients with psoriasis or rheumatoid arthritis are applicable to these patients.
Thirty-two patients with inflammatory bowel disease receiving cumulative methotrexate doses of > or = 1500 mg were studied. Liver chemistry tests were obtained before and during therapy. Twenty patients underwent liver biopsies as recommended for methotrexate-treated patients with psoriasis; the biopsies were reviewed and graded according to Roenigk's criteria for methotrexate-induced hepatotoxicity (a grading system for methotrexate hepatotoxicity in psoriasis patients) by a liver pathologist blinded to the methotrexate dose.
In patients who had liver biopsies, the mean cumulative methotrexate dose was 2633 mg (range, 1500-5410 mg), given for a mean of 131.7 wk (range, 66-281 wk). Nineteen of 20 patients (95%) had mild histological abnormalities (Roenigk's grade I and II), and one patient had hepatic fibrosis (Roenigk's grade IIIB). Abnormal liver chemistry tests, present in 6 of 20 (30%) patients, did not identify the patient with Roenigk's grade IIIB hepatotoxicity.
Cumulative methotrexate doses up to 5410 mg given up to 281 wk in patients with inflammatory bowel disease are associated with little hepatotoxicity. Surveillance liver biopsies based on cumulative methotrexate doses are not warranted in these patients.
甲氨蝶呤目前用于治疗难治性炎症性肠病。本研究旨在评估长期甲氨蝶呤治疗对炎症性肠病患者肝脏的影响，并确定针对银屑病或类风湿关节炎患者制定的通过监测肝活检来监测甲氨蝶呤相关肝毒性的既定指南是否适用于这些患者。
对32例累积甲氨蝶呤剂量≥1500mg的炎症性肠病患者进行研究。在治疗前和治疗期间进行肝功能检查。按照推荐对银屑病患者使用甲氨蝶呤治疗时的方案，20例患者接受了肝活检；肝活检由一位对甲氨蝶呤剂量不知情的肝脏病理学家根据罗宁克（Roenigk）甲氨蝶呤诱导肝毒性标准（一种用于银屑病患者甲氨蝶呤肝毒性的分级系统）进行评估和分级。
接受肝活检的患者中，甲氨蝶呤平均累积剂量为2633mg（范围1500 - 5410mg），平均给药时间为131.7周（范围66 - 281周）。20例患者中有19例（95%）有轻度组织学异常（罗宁克I级和II级），1例患者有肝纤维化（罗宁克IIIB级）。20例患者中有6例（30%）肝功能检查异常，但未识别出罗宁克IIIB级肝毒性患者。
炎症性肠病患者中甲氨蝶呤累积剂量高达5410mg、给药时间长达281周时，肝毒性较小。这些患者无需基于甲氨蝶呤累积剂量进行监测性肝活检。
