Absence of nodular regenerative hyperplasia after low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients

• Published in: Digestive and liver disease 2008-02, Vol.40 (2), p.108-113
• Main Authors: de Boer, N.K.H, Zondervan, P.E, Gilissen, L.P.L, den Hartog, G, Westerveld, B.D, Derijks, L.J.J, Bloemena, E, Engels, L.G.J.B, van Bodegraven, A.A, Mulder, C.J.J
• Format: Article
• Language: English
• Subjects: 6-Thioguanine; 6-Thioguaninenucleotides; Adult; Aged; Antimetabolites, Antineoplastic - adverse effects; Female; Gastroenterology and Hepatology; Hepatotoxicity; Humans; Hyperplasia; Inflammatory bowel disease; Inflammatory Bowel Diseases - drug therapy; Liver - drug effects; Liver - pathology; Male; Middle Aged; Nodular regenerative hyperplasia; Prospective Studies; Thioguanine - administration & dosage; Thioguanine - adverse effects; TPMT; Treatment Outcome
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2007.10.013

Abstract Background The use of 6-thioguanine has been proposed as a rescue drug for inflammatory bowel disease patients. Initial data on short-term efficacy and toxicity of 6-thioguanine were promising; however, these have been challenged by reports concerning its potential hepatotoxic effect (nodular regenerative hyperplasia). We proposed that these histological liver abnormalities may well be dose- or level-dependent. Aims We performed a prospective multi-centre study on the hepatotoxic potential of long-term and (as compared with prior studies) low-dose 6-thioguanine use. Patients Inflammatory bowel disease patients using 6-thioguanine for at least 30 consecutive months and consenting to undergo a liver biopsy were enrolled. Methods Liver biopsy specimens were scored by two pathologists, unaware of clinical data. Laboratory parameters, determined prior to initiation of 6-thioguanine therapy and prior to biopsy, were reviewed. Results Twenty-eight biopsies were analysed. The majority of patients (89%) were azathioprine and/or 6-mercaptopurine intolerant inflammatory bowel disease patients. In 26 patients (93%) no signs of nodular regenerative hyperplasia were detected; in two additional patients nodular regenerative hyperplasia could not be excluded due to inconclusive pathological findings. The mean 6-thioguanine dosage, 6-thioguaninenucleotides level, duration of use and cumulative dosage were 19.5 mg, 564 pmol/8 × 108 RBC, 38 months and 22491 mg, respectively. Conclusions We have demonstrated that low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients is not likely to be associated with induction of nodular regenerative hyperplasia. The induction of nodular regenerative hyperplasia appears to be 6-thioguanine dose or 6-thioguaninenucleotides level dependent.