Azathioprine-Induced Rapid Hepatotoxicity

Objective: To report a case of rapid hepatotoxicity seen within days of initiating azathioprine therapy as a possible adverse reaction. Case Summary: A 62-year-old female with Crohn's disease was being maintained on occasional oral prednisone when more aggressive therapy became indicated. The patient was started on azathioprine and continued a prednisone taper. Liver enzymes became elevated by the third day of therapy. Peak liver enzyme values on day 10 of therapy were aspartate aminotransferase 119 U/L, alanine aminotransferase 210 U/L, and alkaline phosphatase 460 U/L. The patient did not develop any symptoms of hepatotoxicity. Azathioprine was discontinued and liver enzyme levels returned to baseline within 3 weeks. Discussion: Azathioprine hepatotoxicity has been reported previously. A MEDLINE search (1966 to August 2013) found 39 articles related to various types of azathioprine hepatotoxicity. Previous literature predominately involves male patients and a general onset of 2 to 12 months after starting azathioprine therapy. Our case involves a female patient with an onset of days. According to the Naranjo probability scale, this reaction is considered possible, whereas the Council for International Organizations of Medical Sciences Probability Scale categorized this reaction as probable. The concurrent prednisone therapy may have increased the patient's risk of azathioprine hepatotoxicity, but is not likely the sole cause as prior to and after discontinuing azathioprine the liver enzymes remained normal despite prednisone therapy. Conclusions: Prescribers should be aware that monitoring liver enzymes when initiating azathioprine may be warranted within the first week, especially if the patient is taking corticosteroids or other high-risk medications that cause hepatotoxicity.