Mercaptopurine rescue after azathioprine-induced liver injury in inflammatory bowel disease

Aliment Pharmacol Ther. 2010 Jan;31(1):120-4. doi: 10.1111/j.1365-2036.2009.04132.x.

Abstract

Background: Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation.

Aim: To describe the tolerance to mercaptopurine (MP) in patients with previous AZA-related liver injury.

Methods: Retrospective description of 31 patients (14 Crohn's, 17 ulcerative colitis), in which AZA therapy was interrupted because of liver injury, with MP started as alternative therapy.

Results: Mean AZA dose was 2.2 +/- 0.4 mg x kg/day. Median (interquartile range) of AZA exposure when liver injury was detected was 2 months (1-5.2). The type of AZA-related injury was cytolitic in 32%, cholestatic in 39% and mixed in 29%. After a median of 2.5 months (0.7-5.2), the therapy was switched to MP at a mean dose of 1.3 +/- 0.2 mg x kg/day. Median of follow-up of MP therapy was 32 months (8-54). In 87.1% of patients (95%CI: 70-96%), MP was tolerated without further liver injury; of these, 77.4% tolerated full MP doses and 9.7% tolerated lower doses. In a further cohort of 12.9% of patients, (95%CI: 3-29%), liver injury reappeared (two cholestasis, two mixed), 1-3 months after the onset of MP exposure.

Conclusion: The administration of MP is a good alternative in patients with AZA-related liver injury, before thiopurines are definitely discarded.

MeSH terms

  • Adolescent
  • Adult
  • Azathioprine / adverse effects*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Colitis, Ulcerative / complications
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / complications
  • Crohn Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Mercaptopurine / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Mercaptopurine
  • Azathioprine