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

Elizabeth D. Ferucci, Kathy J. Hurlburt, Marlyn J. Mayo, Stephen Livingston, Heike Deubner, James Gove, Julia Plotnik, Brian J. McMahon

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 population-based 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.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalCanadian Journal of Gastroenterology
Volume25
Issue number1
StatePublished - Jan 2011

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thiopurine methyltransferase
Autoimmune Hepatitis
Azathioprine
Leukopenia
Genotype
Enzymes
Therapeutics
Phenotype
Alaska Natives

Keywords

  • Autoimmune liver disease
  • Azathioprine
  • Minority populations
  • Thiopurine methyltransferase

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Azathioprine metabolite measurements are not useful for following treatment of autoimmune hepatitis in Alaska Native and other non-Caucasian people. / Ferucci, Elizabeth D.; Hurlburt, Kathy J.; Mayo, Marlyn J.; Livingston, Stephen; Deubner, Heike; Gove, James; Plotnik, Julia; McMahon, Brian J.

In: Canadian Journal of Gastroenterology, Vol. 25, No. 1, 01.2011, p. 21-27.

Research output: Contribution to journalArticle

Ferucci, Elizabeth D. ; Hurlburt, Kathy J. ; Mayo, Marlyn J. ; Livingston, Stephen ; Deubner, Heike ; Gove, James ; Plotnik, Julia ; McMahon, Brian J. / Azathioprine metabolite measurements are not useful for following treatment of autoimmune hepatitis in Alaska Native and other non-Caucasian people. In: Canadian Journal of Gastroenterology. 2011 ; Vol. 25, No. 1. pp. 21-27.
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AU - Ferucci, Elizabeth D.

AU - Hurlburt, Kathy J.

AU - Mayo, Marlyn J.

AU - Livingston, Stephen

AU - Deubner, Heike

AU - Gove, James

AU - Plotnik, Julia

AU - McMahon, Brian J.

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N2 - 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 population-based 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.

AB - 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 population-based 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.

KW - Autoimmune liver disease

KW - Azathioprine

KW - Minority populations

KW - Thiopurine methyltransferase

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