Incidence, risk factors and clinical course of thiopurine-induced liver injury in patients with inflammatory bowel disease

Aliment Pharmacol Ther. 2005 Nov 1;22(9):775-82. doi: 10.1111/j.1365-2036.2005.02636.x.


Background: The incidence of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease varies in different studies.

Aims: To assess the rate of thiopurine-induced liver toxicity in patients with inflammatory bowel disease; to determine the predictive factors and to characterize its clinical course and management.

Methods: A cohort of 161 patients was prospectively followed for a median of 271 days. Hepatotoxicity was established when alanine transaminase or alkaline phosphatase plasma levels were greater than twice the upper normal limit.

Results: Abnormal liver function was detected in 21 patients (13%; 95% CI: 7-18). Hepatotoxicity occurred in 16 patients (10%; 95% CI: 6-16) after a median of 85 days. In five cases, treatment was withdrawn due to hepatotoxicity. Use of corticosteroids was associated with hepatotoxicity (OR: 4.94; 95% CI: 1.01-23.98) with antitumour necrosis factor concomitant therapy showing a protective role (OR: 0.3; 95% CI: 0.1-3.1). gamma-Glutamyl transferase plasma levels at the onset of hepatotoxicity showed the best predictive value for treatment withdrawal (area under the receiver operating characteristic curve: 0.95).

Conclusions: The incidence of hepatotoxicity in inflammatory bowel disease patients receiving thiopurines is relevant, mainly in patients co-treated with corticosteroids. gamma-Glutamyl transferase plasma level is a useful biomarker in therapy withdrawal prediction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Azathioprine / adverse effects
  • Biomarkers / analysis
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / physiopathology
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / physiopathology
  • Liver / physiopathology
  • Liver Diseases / physiopathology
  • Liver Function Tests
  • Male
  • Mercaptopurine / adverse effects*
  • Middle Aged
  • Prospective Studies
  • Risk Factors


  • Biomarkers
  • Immunosuppressive Agents
  • Mercaptopurine
  • Azathioprine