Diagnosis of 6 mercaptopurine hepatotoxicity post liver transplantation utilizing metabolite assays

Nickolas Kontorinis, Kaushik Agarwal, Gabriel Gondolesi, M. Isabel Fiel, Marian O'Rourke, Thomas D. Schiano

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Azathioprine and 6-mercaptopurine (6 MP) are commonly used as immunosuppression postsolid organ transplantation. Recently, a better understanding of the metabolism of these drugs has developed. 6 Mercaptopurine is metabolized by thiopurine methyl transferase (TPMT) which is under the control of a common genetic polymorphism. Genetic testing and measurement of levels of 6 MP metabolites allow identification of patients at risk of toxicity. We report two cases of cholestatic hepatocellular injury associated with 6 MP toxicity occurring after orthotopic liver transplantation. Cholestasis developed after the introduction of 6 MP. Patients underwent extensive investigation and 6 MP toxicity was considered only after all other causes had been excluded. Thiopurine methyl transferase alleles identified on genetic testing were normal as were the 6 thioguanine levels. However, 6-methyl mercaptopurine levels were significantly elevated into the toxic range. Cholestasis resolved within a few weeks of drug withdrawal. 6 Mercaptopurine hepatotoxicity can present with a variety of clinical, biochemical and histological manifestations post OLT and should be considered as a cause of liver enzyme elevation. Monitoring of 6 MP metabolite levels in addition to TPMT allele testing is useful to prevent 6 MP toxicity and to help guide therapy.

Original languageEnglish
Pages (from-to)1539-1542
Number of pages4
JournalAmerican Journal of Transplantation
Volume4
Issue number9
DOIs
StatePublished - Sep 2004
Externally publishedYes

Keywords

  • 6 methyl mercaptopurine
  • 6 thioguanine
  • Azathioprine
  • Cholestasis

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