Azathioprine
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Hepatotoxicity: case report A 34-year-old woman with Crohn’s disease developed hepatotoxicity during treatment with azathioprine. The woman reported watery rectal leakage and a colonoscopy revealed acute on chronic inflammatory changes of her pouch. She started receiving azathioprine 100 mg/day and, 2 weeks later, she presented with a 2-day history of abdominal pain, nausea and vomiting. On examination, she had hypotension, tachycardia, shock-fist tenderness of her abdomen and tender erythematous nodules on her extremities. Laboratory tests on hospital day 1 revealed the following: AST 5978, ALT 4858, ALT 121, bilirubin 1.6, direct bilirubin 1.2, albumin 3.3, creatinine 2.5, blood urea nitrogen 37, WBC count 2.5 and prothrombin time 25.2 seconds. She had a 6-thioguanine nucleotide level of 99 and a 6-methylmercaptopurine level of 1003. A CT scan showed diffuse hepatic steatosis and a Doppler ultrasound showed patent portal and hepatic veins. Erythema nodosum was revealed by skin biopsy. Azathioprine was discontinued and the woman received supportive care. Three days later, her liver function improved with the following results: AST 114, ALT 1194, ALT 105, bilirubin 0.6, direct bilirubin 0.4, albumin 2.7, creatinine 0.6, blood urea nitrogen 14, WBC count 10.1 and prothrombin time 16.8 seconds. [Patient outcome not stated.] Author comment: "This case of [azathioprine]-induced hepatotoxicity was unique in that liver toxicity reflected an abrupt non-cholestatic hypersensitive mechanism of hepatitis. Furthermore, low levels of [6-thioguanine nucleotide] and [6-methylmercaptopurine] suggested low risk for toxicity, raising a suspicion for an unknown metabolic pathway by which [azathioprine] induces acute liver injury without cholestasis." Koczka CP, et al. Acute noncholestatic azathioprine induced hepatotoxicity in a female with Crohns disease. American Journal of Gastroenterology 102 (Suppl. 2): 801083788 S281 abstr. 449, Sep 2007 [abstract] - USA
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Reactions 27 Oct 2007 No. 1175
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