کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3314838 | 1211221 | 2006 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Utility of thiopurine methyltransferase genotyping and phenotyping, and measurement of azathioprine metabolites in the management of patients with autoimmune hepatitis Utility of thiopurine methyltransferase genotyping and phenotyping, and measurement of azathioprine metabolites in the management of patients with autoimmune hepatitis](/preview/png/3314838.png)
Background/AimsAzathioprine is a key drug in the management of autoimmune hepatitis (AIH), with effects mediated via conversion to 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP), the latter controlled by thiopurine methyltransferase (TPMT). Our aims were to evaluate the role of TPMT genotyping and phenotyping and to examine 6-TG and 6-MMP metabolite levels in patients with AIH.MethodsTPMT genotyping and phenotyping was performed on 86 patients with AIH, and metabolites evaluated in assessable patients.ResultsEighty-six patients with AIH received azathioprine; 22 developed toxicity and 4/22 were heterozygous for TPMT alleles. Cirrhosis was more common amongst patients who developed toxicity (12/22 (54.5%) versus 19/64 (29.6%), P = 0.043). Patients who required persistent prednisone at equivalent azathioprine doses had a higher mean fibrosis stage (P = 0.044). TPMT activity, but not metabolites, was lower in patients with stage III/IV fibrosis versus stage I/II fibrosis (30 ± 1.92 versus 35.2 ± 1.93, P = 0.044). Azathioprine dose significantly correlated with measured 6-TG levels (r = 0.409, P < 0.0001) and 6-MMP levels (r = 0.387, P < 0.001).ConclusionsAdvanced fibrosis but not TPMT genotype or activity predicts azathioprine toxicity in AIH. Overlap in 6-TG and 6-MMP metabolite levels is noted whether or not steroid therapy is used to maintain remission.
Journal: Journal of Hepatology - Volume 45, Issue 4, October 2006, Pages 584–591