title: Changes in liver biochemistry during methotrexate use for inflammatory bowel disease.
abstract: OBJECTIVE
  We aimed to characterize the spectrum of liver enzyme test (LET) abnormalities that occur while using methotrexate for inflammatory bowel disease (IBD).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Fournier
authors.forename: Julianne
authors.initials: J
authors.lastname: Klein
authors.forename: Gerald Y
authors.initials: GY
authors.lastname: Minuk
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008111:Liver Function Tests; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D004791:Enzyme Inhibitors; D008727:Methotrexate