{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:00:31Z","timestamp":1778313631688,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>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\u2010methyltransferase (TPMT), the key detoxifying enzyme of thiopurine metabolism. We report here a case of thiopurine\u2010induced ductopenia with a comprehensive pharmacological analysis on thiopurine metabolism. A 34\u2010year\u2010old 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\u2010thioguanine nucleotides (6\u2010TGN) level and a dramatically increased 6\u2010methylmercaptopurine ribonucleotides (6\u2010MMPN) level, together with an unfavourable [6\u2010MMPN:6\u2010TGN] metabolite ratio and a high TPMT activity. After a total of about 6\u00a0months 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\u2010MMPN blood level, due to unusual thiopurine metabolism (switched metabolism). Early therapeutic drug monitoring with measurement of 6\u2010TGN and 6\u2010MMPN blood levels may help physicians to identify patients at risk of similar duct injury.<\/jats:p>","DOI":"10.1111\/bcp.15797","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T05:40:21Z","timestamp":1684820421000},"page":"2625-2630","source":"Crossref","is-referenced-by-count":5,"title":["Azathioprine\u2010induced vanishing bile duct syndrome: The value of early thiopurine metabolism assessment"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-3571","authenticated-orcid":false,"given":"Laurent","family":"Chouchana","sequence":"first","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance, Service de Pharmacologie p\u00e9rinatale, p\u00e9diatrique et adulte, H\u00f4pital Cochin, AP\u2010HP.Centre Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3571-7277","authenticated-orcid":false,"given":"Benoit","family":"Terris","sequence":"additional","affiliation":[{"name":"Service de Pathologie, H\u00f4pital Cochin, AP\u2010HP.Centre Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3316-8785","authenticated-orcid":false,"given":"Philippe","family":"Sogni","sequence":"additional","affiliation":[{"name":"Service d'h\u00e9patologie, H\u00f4pital Cochin, AP\u2010HP.Centre Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2045-4742","authenticated-orcid":false,"given":"Jean\u2010Marc","family":"Treluyer","sequence":"additional","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance, Service de Pharmacologie p\u00e9rinatale, p\u00e9diatrique et adulte, H\u00f4pital Cochin, AP\u2010HP.Centre Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6031-574X","authenticated-orcid":false,"given":"Nathalie","family":"Costedoat\u2010Chalumeau","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence maladies auto\u2010immunes et syst\u00e9miques rares d'Ile de France, D\u00e9partement de M\u00e9decine interne, H\u00f4pital Cochin, AP\u2010HP.Centre Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cit\u00e9 (CRESS)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9102-2667","authenticated-orcid":false,"given":"Marie\u2010Anne","family":"Loriot","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Pharmacog\u00e9n\u00e9tique, Service de Biochimie, H\u00f4pital europ\u00e9en Georges 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