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A systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel disease.: 6-thioguanine-related hepatotoxicity in inflammatory bowel disease

Alexander Teml 1, 2 Matthias Schwab 2, 3 Daan Hommes 4 Sven Almer 5 Milan Lukas 6 Thomas Feichtenschlager 7 Timothy Florin 8 Julia Seiderer 9 Wolfgang Petritsch 10 Bernd Bokemeyer 11 Wolfgang Kreisel 12 Klaus Herrlinger 13 Peter Knoflach 14 Bruno Bonaz 15 Thomas Klugmann 16 Hans Herfarth 17 Nikolaus Pedarnig 18 Walter Reinisch 1, *
* Corresponding author
1 Medizinische Universität Wien = Medical University of Vienna
2 Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart]
3 Department of Clinical Pharmacology
4 Leiden University Medical Center (LUMC)
5 Division of Gastroenterology and Hepatology/IMK
6 Charles University [Prague]
7 Krankenhaus Rudolfstiftung
8 Mater Health Services' Adult Hospital
9 University-Hospital Munich-Großhadern
10 Institute of human genetics
11 Gastroenterologische Gemeinschaftspraxis Minden
12 Klinikum Freiburg
13 Robert Bosch Hospital
14 Krankenhaus der Barmherzigen Schwestern
15 Département d'hépato-gastroentérologie
16 Internistische Gemeinschaftspraxis
17 UR - Universität Regensburg
18 Unidata Geodesign GmbH
Abstract : OBJECTIVE: Drug-induced liver injury was recently reported as a major complication leading to hepatic nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease (IBD) and 6-thioguanine (6-TG) therapy. The aim of the study was to evaluate the prevalence of 6-TG-related hepatotoxicity in a large multi-centered IBD population by means of a systematic online survey. METHODS: Clinical and laboratory data, imaging techniques (sonography, CT, MRI) and histology of liver biopsies were surveyed in IBD patients treated with 6-TG. The decision on whether liver imaging and/or liver biopsy were performed was exclusively at the discretion of the investigator. RESULTS: 6-TG use was fully documented in 296 patients (median treatment duration 56 weeks, range < 1-207). Laboratory signs of drug-induced liver injury were found in 43 patients (14.5%). Liver imaging revealed pathologic results in 68/176 patients (38.6%). Liver biopsy was performed in a subset of 60 patients; using silver-reticulin staining (n = 59), NRH was considered in 16 patients (27.1%). Age was the only independent, albeit weak, risk factor for development of NRH. CONCLUSION: This large online survey confirms the strong association between 6-TG treatment and the significant risk of development of NRH in patients with IBD. The definitive diagnosis of NRH depends solely upon liver biopsy.
Keywords : thiopurines 6-thioguanine drug-induced liver injury inflammatory bowel disease nodular regenerative hyperplasia thiopurines.
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https://www.hal.inserm.fr/inserm-00388043
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Alexander Teml, Matthias Schwab, Daan Hommes, Sven Almer, Milan Lukas, et al.. A systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel disease.: 6-thioguanine-related hepatotoxicity in inflammatory bowel disease. Wiener Klinische Wochenschrift, Springer Verlag, 2007, 119 (17-18), pp.519-26. ⟨10.1007/s00508-007-0841-0⟩. ⟨inserm-00388043⟩

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