Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease

Am J Gastroenterol. 2000 Nov;95(11):3150-6. doi: 10.1111/j.1572-0241.2000.03287.x.


Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Adult
  • Biopsy
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / pathology
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / drug therapy*
  • Female
  • Folic Acid Antagonists / administration & dosage
  • Folic Acid Antagonists / adverse effects*
  • Folic Acid Antagonists / therapeutic use
  • Humans
  • Liver / pathology
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Time Factors


  • Folic Acid Antagonists
  • Methotrexate