Predictors of azathioprine toxicity in children with autoimmune hepatitis

Azathioprine (AZA) is an important steroid-sparing drug in the management of autoimmune hepatitis (AIH). Avoidance of its adverse events that could be severe and carry a risk of mortality in a few cases is important, preferably with cheap and easy assessments that could be feasible in developing countries with the unavailability of molecular assays. Assessment of thiopurine methyltransferase (TPMT), the key enzyme for the inactivation of AZA, as a predictor of AZA toxicity had been a matter of conflict. This work aimed to study the role of TPMT serum level assessment and other host-, disease-, and treatment-related factors in predicting AZA toxicity.

Sixty-six children with AIH, divided into two groups, were recruited. Group 1 included twelve children with AZA toxicity and group 2 included fifty-four children without AZA toxicities. Both groups were compared for demographic, clinical, laboratory, histopathological, and treatment-related factors, and serum TPMT level, measured by ELISA.

TPMT serum level was comparable in both groups (p = 0.363). Duration of treatment until enzyme normalization and duration of AZA therapy were significantly associated with AZA toxicity (p = 0.007 and p = 0.01, respectively). At the first follow-up treatment with AZA, total leucocyte count (TLC) and neutrophil counts were significantly lower in group 1 (p = 0.005 and p = 0.002, respectively). Moreover, the percentage reduction of TLC and neutrophil counts were significantly higher in group 1 (p < 0.001, for both).

Monitoring for AZA adverse events in those with the defined predictors of AZA-related adverse events is more important than TPMT assessment.