Azathioprine-induced vanishing bile duct syndrome: The value of early thiopurine metabolism assessment.
ductopenia
hepatitis
pharmacogenomics
pharmacovigilance
thiopurine
vanishing bile duct syndrome
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
13
05
2023
received:
03
03
2023
accepted:
17
05
2023
medline:
21
7
2023
pubmed:
23
5
2023
entrez:
23
5
2023
Statut:
ppublish
Résumé
About 15% to 28% of patients treated with thiopurines experienced adverse drug reactions, such as haematological and hepatic toxicities. Some of these related to the polymorphic activity of the thiopurine S-methyltransferase (TPMT), the key detoxifying enzyme of thiopurine metabolism. We report here a case of thiopurine-induced ductopenia with a comprehensive pharmacological analysis on thiopurine metabolism. A 34-year-old woman, with a medical history of severe systemic lupus erythematosus with recent introduction of azathioprine therapy, presented with mild fluctuating transaminase blood levels consistent with a hepatocellular pattern, which evolved to a cholestatic pattern over the next weeks. A blood thiopurine metabolite assay revealed low 6-thioguanine nucleotides (6-TGN) level and a dramatically increased 6-methylmercaptopurine ribonucleotides (6-MMPN) level, together with an unfavourable [6-MMPN:6-TGN] metabolite ratio and a high TPMT activity. After a total of about 6 months of thiopurine therapy, a transjugular liver biopsy revealed a ductopenia, and azathioprine discontinuation led to further clinical improvement. In line with previous reports from the literature, our case supports the fact that ductopenia is a rare adverse drug reaction of azathioprine. The mechanism of reaction is unknown but may involve high 6-MMPN blood level, due to unusual thiopurine metabolism (switched metabolism). Early therapeutic drug monitoring with measurement of 6-TGN and 6-MMPN blood levels may help physicians to identify patients at risk of similar duct injury.
Substances chimiques
Azathioprine
MRK240IY2L
Immunosuppressive Agents
0
Thioguanine
FTK8U1GZNX
Thionucleotides
0
Methyltransferases
EC 2.1.1.-
Mercaptopurine
E7WED276I5
Guanine Nucleotides
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
2625-2630Informations de copyright
© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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