title: The long-term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis.
abstract: OBJECTIVE
  To determine if the long-term use of methotrexate (MTX) in juvenile rheumatoid arthritis (JRA) is associated with the development of significant liver fibrosis, and to describe the presence of risk factors for liver fibrosis in patients with JRA.
  
  
  METHODS
  Needle biopsies of the liver were performed on a cross-section cohort of 14 patients with JRA who had received a total cumulative dose of MTX that was either > 3,000 mg or > 4,000 mg/1.73 m2 of body surface area. Biopsy samples were independently graded according to the Roenigk Classification Scale by 2 pathologists. The presence of risk factors for MTX hepatotoxicity, especially biochemical abnormalities reflective of liver injury and alcohol consumption, were assessed.
  
  
  RESULTS
  Thirteen biopsy samples (93%) were classified as grade I, and 1 (7%) as grade II; none demonstrated significant fibrosis. However, histologic abnormalities were found in 13 biopsy samples (93%). Only 2 patients (14%) consumed more than 1 alcoholic drink per month. Thirteen patients (93%) had biochemical abnormalities while being treated with MTX, but only 5 patients (36%) had at least 1 determination in which the aspartate or alanine aminotransferase elevation was > 3 times the upper limit of normal.
  
  
  CONCLUSIONS
  Long-term use of MTX for JRA does not appear to be associated with the development of significant liver fibrosis. Although nearly all patients had minor histologic changes, no significant clinical consequences were apparent. A prospective study of a larger population will more accurately define the incidence of MTX-related liver fibrosis and appropriate monitoring guidelines in JRA.
authors.affiliation: Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hashkes
authors.forename: W F
authors.initials: WF
authors.lastname: Balistreri
authors.forename: K E
authors.initials: KE
authors.lastname: Bove
authors.forename: E T
authors.initials: ET
authors.lastname: Ballard
authors.forename: M H
authors.initials: MH
authors.lastname: Passo
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy*; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D012709:Serum Albumin
chemical_list: D018501:Antirheumatic Agents; D012709:Serum Albumin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008727:Methotrexate