Azathioprine metabolite measurements are not useful in following treatment of autoimmune hepatitis in Alaska Native and other non-Caucasian people.
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.


CONCLUSIONS
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.
Alaska Native Tribal Health Consortium, Anchorage, Alaska 99508, USA. edferucci@anthc.org
Elizabeth D
ED
Ferucci
Kathy J
KJ
Hurlburt
Marlyn J
MJ
Mayo
Stephen
S
Livingston
Heike
H
Deubner
James
J
Gove
Julia
J
Plotnik
Brian J
BJ
McMahon
D000328:Adult; D000413:Alaska; D001379:Azathioprine / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D019693:Hepatitis, Autoimmune / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007198:Indians, North American; D008297:Male; D015122:Mercaptopurine / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged
D015415:Biomarkers; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine
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