Fournier MR, Klein J, Minuk GY et al. Am J Gastroenterol 2010;105:1620–6.
The proper monitoring regimen for methotrexate use remains controversial. This series from the gastroenterology literature examined the hepatotoxicity of methotrexate in inflammatory bowel disease. Most cases of transaminase elevation resolved without dose modification, and the 17 liver biopsies undertaken were without worrisome pathological changes; however, the small sample size (n=87) limits the generalizability of the findings of this study.
The major clinical toxicity problem associated with methotrexate use is hepatotoxicity, which, in rare cases, can lead to cirrhosis. Several sets of recommendations have been proposed for liver function test (LFT) monitoring and biopsy in these patients, depending on the disease and source group. Since no formal recommendations are available for methotrexate use in inflammatory bowel disease (IBD), this group examined their single-center experience with 87 patients who had used methotrexate as IBD therapy for >4 weeks (mean 81 weeks) and who had regular LFT monitoring. Most patients had been started on methotrexate 25 mg weekly via a parenteral route. Folic acid was supplemented in 76 patients (87%). Of the 87 patients, 37 had been exposed to a total dose of >1500 mg. Sixty-seven patients (77%) had normal LFTs at drug initiation, and, of these, 76% continued to have normal LFTs throughout the course of therapy. When observed, elevation of LFTs normalized without dose adjustment in 88% of patients. One patient exposed to >3000 mg methotrexate underwent three liver biopsies for persistent elevation of LFTs, demonstrating some progressive fibrous change, but these were mild and therapy was continued. Among 20 (23%) patients started on methotrexate in the face of abnormal LFTs, 45% had normalizing of their LFTs while 45% experienced worsening values. Overall, 17 liver biopsies were performed: 14 due to a cumulative methotrexate dose >1500 mg and three for elevated LFTs on methotrexate (described above). Fifteen of the 17 showed normal histology, while two showed a mild fibrotic change not requiring alteration of therapy.