Utility of Monitoring Azathioprine Metabolites in the Management of Children with Autoimmune Hepatitis

Aim: Although monitoring of the active metabolite (6-thioguanine or 6-TG) and hepatotoxic metabolite (6 methylmercaptopurine or 6-MMP) of the drugs azathioprine (AZA) or 6-mercaptopurine is well-established in children with inflammatory bowel disease, there is little information about the utility of this practice in children with AIH. Objectives: The purpose of this single center retrospective study was two-fold: 1) To determine if metabolite monitoring (MM) was associated with improved clinical outcome and 2) To determine levels of 6-TG associated with remission. Methods: Chart review was performed of all patients ages 0-21 years at the Johns Hopkins Hospital with definite or probable AIH from 1991 to 2012 seen over two years of follow up. Results: Twenty-one patients with AIH met the inclusion criteria of pre-transplant state and treatment with AZA or 6-MP. 10 patients did not have MM (Group 1); 11 patients had MM at least once (Group 2). Average AZA dose for Group 1 patients was 1.2 (0.6-1.8) mg/kg/day vs. 1.9 (1.3-2.9) for Group 2 patients (P=0.002). 4/10 (40%) Group 1 patients achieved remission vs. 7/11 (64%) Group 2 patients (P=0.39). The average 6-TG level for Group 2 remission patients was 162.7 pmol/8 × 108 red blood cells (RBC) (41.5-316; N=7). One patient developed liver failure presumably secondary to AZA-cholestasis (6-MMP level of 6792 pmol/8 × 108 RBC), since it resolved with discontinuation of AZA. Conclusions: MM in children with AIH may prove useful for determining 6TG levels associated with remission, permit dose escalation as necessary, and assist in determination of AZA toxicity.