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* = Presenting author

P437 Short term prevalence of nodular regenerative hyperplasia of the liver in IBD patients treated with allopurinol-thiopurine combination therapy

M. Seinen*1, D. van Asseldonk1, N. de Boer1, G. Bouma1, C. Mulder1, E. Bloemena2, A. van Bodegraven3

1VU University Medical Centre, Gastroenterology and Hepatology, Amsterdam, Netherlands, 2VU University Medical Center, Pathology, Amsterdam, Netherlands, 3ORBIS Medical Center, Internal Medicine, Gastroenterology, and Geriatrics, Sittard, Netherlands

Background

Tioguanine has been associated with nodular regenerative hyperplasia (NRH) of the liver. Combination therapy of allopurinol and adapted dose conventional thiopurine leads to a pharmacokinetic profile partly comparable with that of tioguanine ((high 6-thioguanine nucleotides (6-TGN) and low 6-methylmercaptopurine (6-MMPR) concentrations)). Therefore, combination therapy of allopurinol and conventional thiopurines may induce NRH of the liver in a comparative way. We assessed short term prevalence of NRH in IBD-patients treated with allopurinol-thiopurine combination therapy.

Methods

This was an observational, single-centre cross-sectional study. All adult IBD-patients who were treated at least one year with allopurinol-thiopurine combination therapy were eligible. Subjects were identified at the Outpatients' clinic and they were consecutively invited to participate. All patients underwent a liver biopsy, and venous blood was drawn to measure haematological and hepatic parameters, including thrombocyte count and alkaline phosphatase, but also to determine thiopurine metabolite concentrations. Histopathology was assessed by an experienced hepatopathologist.

Results

Eighteen IBD-patients, of which thirteen were diagnosed with Crohn's disease were included. The median age at inclusion was 36 year (IQR 25-42). Combination therapy was initiated in nine patients as a result of elevated transaminase activities during thiopurine monotherapy. The median duration of combination therapy at inclusion was 24 months (IQR 20-28). The median 6-TGN and 6-MMPR level was 685 pmolx108 RBC (IQR 498-940) and 305 pmolx108 RBC (IQR 198-608). In none of the patients NRH was observed; sinusoidal dilatation was observed in four patients. No trombocytopenia was observed.

Conclusion

Short term prevalence of NRH in IBD-patients who were treated with a combination of allopurinol and low dose conventional thiopurine, was low, as in none of the included eighteen patients NRH was observed.