OJGas  Vol.3 No.6 , October 2013
Azathioprine induced liver cirrhosis: An unusual side effect
ABSTRACT
In recent years, the hepatotoxic potential of thiopurines, in particular 6-thioguanine (6-TG), has been discussed in literature. However, cirrhosis was exceptionally reported. We report the case of a 56-year-old woman with ileocaecal Crohn’s disease treated with azathioprine. After taking azathioprine (2 mg/kg daily) for four years, she underwent surgical treatment for acute intestinal obstruction. In peroperative, we noticed a cirrhotic liver. A surgical biopsy was performed and the diagnosis of cirrhosis was confirmed. Autoimmune and viral liver diseases were ruled out by laboratory parameters. Therefore, Azathioprine is believed to be the causative factor for inducing liver cirrhosis. Thus, treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle.

Cite this paper
Ben Slama Trabelsi, A. , Hamami, E. , Ksiaa, M. , Souguir, A. , Ben Mabrouk, M. , Brahem, A. , Jmaa, A. and Ajmi, S. (2013) Azathioprine induced liver cirrhosis: An unusual side effect. Open Journal of Gastroenterology, 3, 295-297. doi: 10.4236/ojgas.2013.36050.
References
[1]   Podolsky, D.K. (2002) Inflammatory bowel disease. New England Journal of Medicine, 347, 417-429.
http://dx.doi.org/10.1056/NEJMra020831

[2]   Markowitz, J., Grancher, K., Kohn, N. and Daum, F. (2002) Immunomodulatory therapy for pediatric inflammatory bowel disease: Changing patterns of use, 1990-2000. American Journal of Gastroenterology, 97, 928-932.

[3]   Boer, N.K.H., Mulder, C.J.J. and van Bodegraven, A.A. (2005) Myelotoxicity and hepatotoxicity during azathioprine therapy. Netherlands Journal of Medicine, 63, 444-446.

[4]   Pearson, D.C., May, G.R., Fick, G.H. and Sutherland, L.R. (1995) Azathioprine and 6-mercaptopurine in Crohn’s disease. A meta-analysis. Annals of Internal Medicine, 123, 132-142.
http://dx.doi.org/10.7326/0003-4819-123-2-199507150-00009

[5]   Fraser, A.G., Orchard, T.R. and Jewell, D.P. (2002) The efficacy of azathioprine for the treatment of inflammatory bowel disease: A 30 year review. Gut, 50, 485-489.
http://dx.doi.org/10.1136/gut.50.4.485

[6]   Lowry, P.W., Franklin, C.L., Weaver, A.L., et al. (2001) Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut, 49, 665-670.
http://dx.doi.org/10.1136/gut.49.5.665

[7]   Gisbert, J.P., González-Lama, Y. and Maté, J. (2007) Thiopurine-induced liver injury in patients with inflamematory bowel disease: A systematic review. American Journal of Gastroenterology, 102, 1518-1527.
http://dx.doi.org/10.1111/j.1572-0241.2007.01187.x

[8]   Macdonald, A. (2006) Omega-3 fatty acids as adjunctive therapy in Crohns disease. Gastroenterology Nursing, 29, 295-301.
http://dx.doi.org/10.1097/00001610-200607000-00005

[9]   Cuffari, C., Dassopoulos, T., Turnbough, L., Thompson, R.E. and Bayless, T.M. (2004) Thiopurine methyltransferase activity influences clinical response to azathioprine in inflammatory bowel disease. Clinical Gastroenterology and Hepatology, 2, 410-417.
http://dx.doi.org/10.1016/S1542-3565(04)00127-2

[10]   Kiefer, K. and El-Matary, W. (2009) 6 mercaptopurine as an alternative to azathioprine in azathioprine-induced hepatoxicity. Inflammatory Bowel Diseases, 15, 318-319.
http://dx.doi.org/10.1002/ibd.20603

[11]   Boson, W.L., Romano-Silva, M.A., Correa, H., Falcao, R.P., Teixeira-Vidigal, P.V. and De Marco, L. (2003) Thiopurine methyltransferase polymorphisms in a Brazilian population. Pharmacogenomics Journal, 3, 178-182. http://dx.doi.org/10.1038/sj.tpj.6500175

[12]   Dubinsky, M.C., Lamothe, S. and Yang, H.Y. (2000) Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology, 118, 705-713.
http://dx.doi.org/10.1016/S0016-5085(00)70140-5

[13]   Dubinsky, M.C., Yang, H. and Hassard, P.V. (2002) 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology, 122, 904-915.
http://dx.doi.org/10.1053/gast.2002.32420

[14]   Hosni-Ahmed, A., Barnes, J.D., Wan, J. and Jones, T.S. (2011) Thiopurine methyltransferase predicts the extent of cytotoxicty and DNA damage in astroglial cells after thioguanine exposure. PLoS One, 6, e29163.
http://dx.doi.org/10.1371/journal.pone.0029163

[15]   Coulthard, S. and Hogarth, L. (2005) The thiopurines: An update. Investigational New Drugs, 23, 523-532.
http://dx.doi.org/10.1007/s10637-005-4020-8

[16]   Gastal, G.R., Moreira, S., Noble, C.F., Ferreira, L.E., Franca, P.H. and Pinho, M. (2012) Toxicity of azathioprine: Why and when? Analysis of the prevalence of polymorphism in Joinville, SC, Brazil. Arquivos de Gastroenterologia, 49, 130-134.
http://dx.doi.org/10.1590/S0004-28032012000200007

 
 
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