BACKGROUND: In autoimmune hepatitis (AIH) patients treated with azathioprine, the utility of measuring thiopurine methyltransferase (TPMT) and azathioprine metabolites has been limited. OBJECTIVE: To evaluate the association between TPMT genotype and enzyme activity, and the impact of TPMT enzyme activity on levels of azathioprine metabolites and leukopenia to assess the clinical utility of monitoring azathioprine metabolites in Alaska Native and other non-Caucasian AIH patients. METHODS: Individuals with AIH were recruited at the Alaska Native Medical Center (Alaska, USA) and the University of Texas Southwestern Medical Center (Texas, USA). Identification of TPMT genotype and measurement of enzyme activity were performed. The metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) were measured in participants who were on azathioprine, and the associations with disease remission and leukopenia were assessed. RESULTS: Seventy-one patients with AIH were included. The distribution of TPMT genotypes was similar to that reported in other populationbased studies. TPMT genotype and phenotype were strongly associated (P<0.0001). Levels of 6-TGN and 6-MMP correlated with azathioprine dose only in individuals with normal TPMT enzyme activity. Patients with leukopenia due to azathioprine were no more likely to have abnormal TPMT enzyme levels than those without leukopenia (P=1.0). No specific level of 6-TGN metabolites was associated with remission or leukopenia. DISCUSSION: Results of the present study were consistent with previous studies in Caucasian populations. TPMT genotype and phenotype correlated well, and levels of 6-TGN and 6-MMP metabolites were not associated with remission of AIH or toxicity of azathioprine. CONCLUSIONS: The present study confirmed the limited utility of monitoring levels of azathioprine metabolites in AIH patients.
BACKGROUND: In autoimmune hepatitis (AIH) patients treated with azathioprine, the utility of measuring thiopurine methyltransferase (TPMT) and azathioprine metabolites has been limited. OBJECTIVE: To evaluate the association between TPMT genotype and enzyme activity, and the impact of TPMT enzyme activity on levels of azathioprine metabolites and leukopenia to assess the clinical utility of monitoring azathioprine metabolites in Alaska Native and other non-Caucasian AIH patients. METHODS: Individuals with AIH were recruited at the Alaska Native Medical Center (Alaska, USA) and the University of Texas Southwestern Medical Center (Texas, USA). Identification of TPMT genotype and measurement of enzyme activity were performed. The metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) were measured in participants who were on azathioprine, and the associations with disease remission and leukopenia were assessed. RESULTS: Seventy-one patients with AIH were included. The distribution of TPMT genotypes was similar to that reported in other populationbased studies. TPMT genotype and phenotype were strongly associated (P<0.0001). Levels of 6-TGN and 6-MMP correlated with azathioprine dose only in individuals with normal TPMT enzyme activity. Patients with leukopenia due to azathioprine were no more likely to have abnormal TPMT enzyme levels than those without leukopenia (P=1.0). No specific level of 6-TGN metabolites was associated with remission or leukopenia. DISCUSSION: Results of the present study were consistent with previous studies in Caucasian populations. TPMT genotype and phenotype correlated well, and levels of 6-TGN and 6-MMP metabolites were not associated with remission of AIH or toxicity of azathioprine. CONCLUSIONS: The present study confirmed the limited utility of monitoring levels of azathioprine metabolites in AIH patients.
Authors: Michael A Heneghan; Michael L Allan; Jeffrey D Bornstein; Andrew J Muir; David A Tendler Journal: J Hepatol Date: 2006-06-23 Impact factor: 25.083
Authors: F Alvarez; P A Berg; F B Bianchi; L Bianchi; A K Burroughs; E L Cancado; R W Chapman; W G Cooksley; A J Czaja; V J Desmet; P T Donaldson; A L Eddleston; L Fainboim; J Heathcote; J C Homberg; J H Hoofnagle; S Kakumu; E L Krawitt; I R Mackay; R N MacSween; W C Maddrey; M P Manns; I G McFarlane; K H Meyer zum Büschenfelde; M Zeniya Journal: J Hepatol Date: 1999-11 Impact factor: 25.083
Authors: Elke M Hennes; Mikio Zeniya; Albert J Czaja; Albert Parés; George N Dalekos; Edward L Krawitt; Paulo L Bittencourt; Gilda Porta; Kirsten M Boberg; Harald Hofer; Francesco B Bianchi; Minoru Shibata; Christoph Schramm; Barbara Eisenmann de Torres; Peter R Galle; Ian McFarlane; Hans-Peter Dienes; Ansgar W Lohse Journal: Hepatology Date: 2008-07 Impact factor: 17.425
Authors: Lilla M Roy; Richard M Zur; Elizabeth Uleryk; Chris Carew; Shinya Ito; Wendy J Ungar Journal: Pharmacogenomics Date: 2016-03-29 Impact factor: 2.533