A Lower 6MMP/6TG Ratio may be a Therapeutic Target in Pediatric Autoimmune Hepatitis

Background: Azathioprine(AZA) is the mainstay of maintenance therapy in pediatric autoimmune hepatitis(AIH). However, the use of thiopurines metabolites to individualize therapy and avoid toxicity has not been clearly defined. Methods: Retrospective analysis of children ≤18 years diagnosed with AIH between January 2001 and 2016. Standard definitions were used for treatment response and disease flare. Thiopurine metabolite levels were correlated with the corresponding LFT. Results: 56 children (32 female) were diagnosed with AIH at a median age of 11 years (IQR 9). No difference in 6-thioguanine-nucleotide (6-TG) levels [271(IQR 251) pmol/8 x 108 RBC vs. 224(IQR 147) pmol/8 x 108 RBC, p = 0.06] was observed in children in remission when compared to those who were not in remission. No correlation was observed between the 6-TG and ALT levels (r = - 0.179, p = 0.109) or between 6-methyl-mercaptopurine(6-MMP) and ALT levels (r = 0.139, p = 0.213). The 6-MMP/6–TG ratio was significantly lower in patients who were in remission [2(7) vs. 5(10), p = 0.04]. Using a quartile analysis, we found that having a ratio of

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