Diagnosis of 6 mercaptopurine hepatotoxicity post liver transplantation utilizing metabolite assays.
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.
Kontorinis
Nickolas
N
Recanati-Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY, USA. nickolas.kontorinis@mssm.edu
Agarwal
Kaushik
K
Gondolesi
Gabriel
G
Fiel
M Isabel
MI
O'Rourke
Marian
M
Schiano
Thomas D
TD
D001663:Bilirubin / Q000097:blood; D001711:Biotransformation; D004396:Coloring Agents; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D016031:Liver Transplantation / Q000473:pathology*; D015122:Mercaptopurine / Q000009:adverse effects* / Q000493:pharmacokinetics; D008780:Methyltransferases / Q000378:metabolism; D008875:Middle Aged; D016896:Treatment Outcome
D004396:Coloring Agents; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001663:Bilirubin