Literature DB >> 17188950

Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated with long-term, low dose 6-thioguanine. Some evidence for dose or metabolite level dependent effects?

L P L Gilissen1, L J J Derijks, A Driessen, L P Bos, P M Hooymans, R W Stockbrügger, L G J B Engels.   

Abstract

BACKGROUND: 6-Thioguanine is used in inflammatory bowel disease since 2001, with promising short-term results. In 2003, liver histology of some 6-thioguanine treated patients showed nodular regenerative hyperplasia. Recently, magnetic resonance imaging revealed nodular regenerative hyperplasia in patients with normal histology. AIMS: Investigating the presence of nodular regenerative hyperplasia in long-term 6-thioguanine treated patients. PATIENTS AND METHODS: Inflammatory bowel disease patients, using 6-thioguanine minimally 24 months, were asked to undergo liver biopsy and magnetic resonance imaging.
RESULTS: Fourteen patients used 6-thioguanine minimally 24 months, 13 participated. Mean 6-thioguanine therapy duration, daily dose and 6-thioguanine nucleotide levels were: 36 months, 18.8 mg (0.28 mg/kg) and 705 pmol/8x10(8) erythrocytes, respectively. Liver histology and magnetic resonance imaging showed no nodular regenerative hyperplasia. DISCUSSION: Liver biopsy and magnetic resonance imaging showed no nodular regenerative hyperplasia in these long-term 6-thioguanine treated inflammatory bowel disease patients. 6-thioguanine dose and metabolite levels were lower compared with previous nodular regenerative hyperplasia reports, suggesting dose or metabolite level-dependent effects. Otherwise, nodular regenerative hyperplasia is related with inflammatory bowel disease itself and immunosuppressives, including azathioprine and 6-mercaptopurine.
CONCLUSION: 6-Thioguanine is debated due to nodular regenerative hyperplasia. We found no nodular regenerative hyperplasia in inflammatory bowel disease patients with long-term, low dosed 6-thioguanine, suggesting metabolite level-dependent effects. Therefore, 6-thioguanine still seems useful, but in selected patients, intolerant for other immunosuppressives, low dosed and under close surveillance of metabolite levels and hepatotoxity.

Entities:  

Mesh:

Substances:

Year:  2006        PMID: 17188950     DOI: 10.1016/j.dld.2006.10.007

Source DB:  PubMed          Journal:  Dig Liver Dis        ISSN: 1590-8658            Impact factor:   4.088


  8 in total

Review 1.  Start low, go slow, but don't go this way yet.

Authors:  Brian Bressler; Robert Enns
Journal:  Can J Gastroenterol       Date:  2008-02       Impact factor: 3.522

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

Authors:  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 Reinisch
Journal:  Wien Klin Wochenschr       Date:  2007       Impact factor: 1.704

Review 3.  Use of thiopurines in inflammatory bowel disease.

Authors:  Pascal Frei; Luc Biedermann; Ole Haagen Nielsen; Gerhard Rogler
Journal:  World J Gastroenterol       Date:  2013-02-21       Impact factor: 5.742

4.  Safety and efficacy of the immunosuppressive agent 6-tioguanine in murine model of acute and chronic colitis.

Authors:  Miloslav Kverka; Pavel Rossmann; Helena Tlaskalova-Hogenova; Klara Klimesova; Bindia Jharap; Nanne K de Boer; Rene M Vos; Adriaan A van Bodegraven; Milan Lukas; Chris J Mulder
Journal:  BMC Gastroenterol       Date:  2011-05-05       Impact factor: 3.067

Review 5.  How I treat my inflammatory bowel disease-patients with thiopurines?

Authors:  Berrie Meijer; Chris Jj Mulder; Adriaan A van Bodegraven; Nanne K H de Boer
Journal:  World J Gastrointest Pharmacol Ther       Date:  2016-11-06

Review 6.  Efficacy of thioguanine treatment in inflammatory bowel disease: A systematic review.

Authors:  Berrie Meijer; Chris Jj Mulder; Godefridus J Peters; Adriaan A van Bodegraven; Nanne Kh de Boer
Journal:  World J Gastroenterol       Date:  2016-10-28       Impact factor: 5.742

7.  Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: A systematic review.

Authors:  Linea Natalie Toksvang; Magnus Strøh Schmidt; Sofie Arup; Rikke Hebo Larsen; Thomas Leth Frandsen; Kjeld Schmiegelow; Cecilie Utke Rank
Journal:  PLoS One       Date:  2019-05-24       Impact factor: 3.240

Review 8.  Thiopurines in Inflammatory Bowel Disease. How to Optimize Thiopurines in the Biologic Era?

Authors:  Carla J Gargallo-Puyuelo; Viviana Laredo; Fernando Gomollón
Journal:  Front Med (Lausanne)       Date:  2021-07-16
  8 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.