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Wiener klinische Wochenschrift

, Volume 119, Issue 17–18, pp 519–526 | Cite as

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

  • Alexander Teml
  • Matthias Schwab
  • Daan W. Hommes
  • Sven Almer
  • Milan Lukas
  • Thomas Feichtenschlager
  • Timothy Florin
  • Julia Seiderer
  • Wolfgang Petritsch
  • Bernd Bokemeyer
  • Wolfgang Kreisel
  • Klaus R. Herrlinger
  • Peter Knoflach
  • Bruno Bonaz
  • Thomas Klugmann
  • Hans Herfarth
  • Nikolaus Pedarnig
  • Walter ReinischEmail author
Original Article

Summary

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

6-thioguanine Drug-induced liver injury Inflammatory bowel disease Nodular regenerative hyperplasia Thiopurines 

Eine systematische Studie zur Untersuchung der 6-Thioguanin-assoziierten Hepatotoxizität bei Patienten mit chronisch-entzündlichen Darmerkrankungen

Zusammenfassung

HINTERGRUND: Vor kurzem wurde von Leberveränderungen im Sinne einer nodulär regenerativen Hyperplasie (NRH) als Ausdruck einer 6-Thioguanin (6-TG) assoziierten Hepatotoxizität bei Patienten mit chronisch-entzündlichen Darmerkrankungen (CED) berichtet. Das Ziel dieser multi-zentrischen Internet-Studie war es, die Prävalenz der Hepatotoxizität von 6-TG in einer großen CED-Population zu untersuchen. METHODIK: Klinische Daten, Laborwerte, bildgebende Untersuchungen (Sonographie, CT, MRI) und histologische Ergebnisse von Leberbiopsien wurden bei Patienten mit CED unter Therapie mit 6-TG untersucht. Die Entscheidung zur Durchführung von bildgebenden Untersuchungen und Leberbiopsien lag ausschließlich bei den einzelnen Zentren. ERGEBNISSE: Bei 296 Patienten wurde die Anwendung von 6-TG über einen Zeitraum von 56 Wochen (Median, Spannweite < 1–207) dokumentiert. Laborveränderungen als Zeichen einer Hepatotoxizität wurden bei 43 Patienten (14,5%) beobachtet. Mittels bildgebender Verfahren wurden bei 68/176 Patienten (38,6%) pathologische Ergebnisse gefunden. An 60 Patienten erfolgte eine Leberbiopsie. Mit Durchführung einer Silber-Retikulin Färbung (n = 59) konnte bei 16 Patienten (27,1%) eine NRH gezeigt werden. Höheres Alter war der einzige unabhängige, aber schwache Risikofaktor dafür. SCHLUSSFOLGERUNG: Diese derzeit größte Studie bestätigt den starken Zusammenhang zwischen der Anwendung von 6-TG bei Patienten mit CED und dem signifikanten Risiko für die Entwicklung einer NRH. Die definitive Diagnose der NRH kann nur durch eine Leberbiopsie gestellt werden.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Alexander Teml
    • 1
    • 2
  • Matthias Schwab
    • 2
    • 3
  • Daan W. 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 R. Herrlinger
    • 13
  • Peter Knoflach
    • 14
  • Bruno Bonaz
    • 15
  • Thomas Klugmann
    • 16
  • Hans Herfarth
    • 17
  • Nikolaus Pedarnig
    • 18
  • Walter Reinisch
    • 1
    Email author
  1. 1.Medical University of ViennaAustria
  2. 2.Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, and University of TübingenGermany
  3. 3.Department of Clinical PharmacologyUniversity of TübingenGermany
  4. 4.Leiden University Medical CenterLeidenThe Netherlands
  5. 5.Division of Gastroenterology and Hepatology/IMKLinköping universitySweden
  6. 6.Charles UniversityPragueCzech Republic
  7. 7.Krankenhaus RudolfstiftungViennaAustria
  8. 8.Mater Health Services' Adult HospitalSouth BrisbaneAustralia
  9. 9.University-Hospital Munich-GroßhadernMunichGermany
  10. 10.Medical University of GrazAustria
  11. 11.Gastroenterologische Gemeinschaftspraxis MindenGermany
  12. 12.Klinikum FreiburgGermany
  13. 13.Robert Bosch HospitalStuttgartGermany
  14. 14.Krankenhaus der Barmherzigen SchwesternWelsAustria
  15. 15.CHU de GrenobleGrenoble CedexFrance
  16. 16.Internistische GemeinschaftspraxisLeipzigGermany
  17. 17.University RegensburgGermany
  18. 18.Unidata GeodesignViennaAustria

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