Thiopurine methyltransferase deficiency and azathioprine intolerance in autoimmune hepatitis

Thiopurine methyltransferase deficiency has been associated with intolerance to azathioprine. Our goals were to assess the frequency of enzyme deficiency in autoimmune hepatitis and correlate deficiency states with azathioprine intolerance. Eighty-six patients receiving azathioprine (50-150 mg daily) were evaluated for enzyme activity and azathioprine-related complications. Their findings were compared to 89 similarly treated but untested patients. Thirteen patients (15%) had low thiopurine methyltransferase levels (11.4+/- 0.9 U/ml RBC; range, 3.5-14.9 U/ml RBC). Azathioprine intolerance occurred as commonly in patients with normal or above normal enzyme levels as in patients with below normal levels (12% versus 15%, p = 0.7). Patients treated without enzyme testing had the same frequency of complications (9% versus 13%, p = 0.5) as tested patients. We conclude that routine screening of blood thiopurine methyltransferase levels has a low yield for identifying individual patients at risk for azathioprine toxicity during conventional low dose therapy for autoimmune hepatitis.