Elevation of serum hepatic aminotransferases during treatment of rheumatoid arthritis with low-dose methotrexate. Risk factors and response to folic acid

Scand J Rheumatol. 1999;28(5):273-81. doi: 10.1080/03009749950155454.


Sixty-six rheumatoid arthritis (RA) patients were analyzed retrospectively to assess the incidence and risk factors for elevation of serum hepatic aminotransferases during methotrexate (MTX) therapy. The effect of folate supplementation on serum ALT and RA activity was evaluated prospectively in 14 patients who showed a sustained high serum level of ALT. The frequency of elevation of serum AST or ALT was 4-5 times greater than in patients taking other DMARDs. Multivariate linear regression analysis demonstrated that elevation of ALT was independently associated with sex (female), obesity, baseline ALT, MTX dose, and gastrointestinal side effects. Folate supplementation caused ALT levels to decrease in all patients within 3 months. Eleven patients showed no change of RA activity, but 3 patients dropped out of the study because of the exacerbation of RA. These results suggest that careful monitoring of serum hepatic aminotransferases is necessary in patients with predisposing factors, especially those receiving more than 0.15 mg/kg of MTX weekly. Folate supplementation can reverse the sustained elevation of ALT, but might cause exacerbation of RA in some patients.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / enzymology
  • Aspartate Aminotransferases / blood*
  • Female
  • Folic Acid / therapeutic use
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Liver / enzymology
  • Male
  • Medical Records
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Retrospective Studies


  • Adrenal Cortex Hormones
  • Antirheumatic Agents
  • Histamine H2 Antagonists
  • Folic Acid
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Methotrexate