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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·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·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. [ABSTRACT FROM AUTHOR]