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BACKGROUND/AIMS:Azathioprine is a key drug in the management of autoimmune hepatitis (AIH),with effects mediated via conversion to 6-thioguanine (6-TG) and6-methylmercaptopurine (6-MMP), the latter controlled by thiopurinemethyltransferase (TPMT). Our aims were to evaluate the role of TPMT genotypingand phenotyping and to examine 6-TG and 6-MMP metabolite levels in patientswith AIH. METHODS: TPMT genotyping and phenotyping was performed on 86 patientswith AIH, and metabolites evaluated in assessable patients. RESULTS: Eighty-sixpatients with AIH received azathioprine; 22 developed toxicity and 4/22 wereheterozygous for TPMT alleles. Cirrhosis was more common amongst patients whodeveloped toxicity (12/22 (54.5%) versus 19/64 (29.6%), P=0.043). Patients whorequired persistent prednisone at equivalent azathioprine doses had a highermean fibrosis stage (P=0.044). TPMT activity, but not metabolites, was lower inpatients with stage III/IV fibrosis versus stage I/II fibrosis (30+/-1.92versus 35.2+/-1.93, P=0.044). Azathioprine dose significantly correlated withmeasured 6-TG levels (r=0.409, P<0.0001) and 6-MMP levels (r=0.387,P<0.001). CONCLUSIONS: Advanced fibrosis but not TPMT genotype or activitypredicts azathioprine toxicity in AIH. Overlap in 6-TG and 6-MMP metabolite levelsis noted whether or not steroid therapy is used to maintain remission.Leggil'articolo