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?

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/8 x 10(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. (c) 2006 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.