Hepatic histology of IBD patients following one year of combination therapy with allopurinol and low-dose conventional thiopurines

Nodular regenerative hyperplasia (NRH) of the liver is a histopathological
condition that has been associated with the use of thiopurines and in
particular with 6-thioguanine (6-TG). Combination therapy of allopurinol and
low, adapted dose thiopurine provides a different metabolisation profile of
conventional thiopurine derivatives, resulting in increased 6 thioguanine
nucleotides (6-TGN) concentrations and decreased 6 methyl mercaptopurine
(6-MMP) concentrations. This *corrected* thiopurine metabolism induces
metabolites in a ratio which resembles the observed metabolites levels during
6-TG administration. Therefore, combination therapy of allopurinol and adapted
dose thiopurine might be associated with nodular regenerative hyperplasia of
the liver (NRH). Early stage (presumably reversible) NRH may only be identified
by pathohistological examination. The aim of this study is to determine the 1
years prevalence of NRH in patients treated with combination therapy of
allopurinol and low dose thiopurine and to compare the incidence/prevalence
with the reported findings of 6TG-induced NRH.

To determine the percentage of patients with nodular regenerative hyperplasia
of the liver after at least 1 year of combination therapy of allopurinol and
low dose AZA or MP and to compare this with the reported findings of 6TG
induced NRH

This study will be a single centre observational cross-sectional study. Each
study object will visit the hospital once within the scope of this study. This
study ends when the number of included patients reaches the calculated number
of 22.

Patients will be asked to visit the hospital for one day. They will undergo an
ultrasound of the spleen and liver and subsequently a liver biopsy will be
performed. Blood will be drawn once, physical examination will be performed ans
a questionaire will be conducted. The direct benefit for participating subjects
is that liver biopsy might reveal histological abnormalities, probably related
to the use of combination therapy of allopurinol and low dose thiopurines, that
have not (yet) become clinical apparent. In these cases, alternative
therapeutic options should be considered in order to avoid further liver
abnormalities, and if reversible, allow for regeneration of normal
architecture. The burden for the patient is the extra hospital visit and a
liver biopsy which holds a complication risk of an estimated maximum of
approximately 1.0% 1. At the VU University Hospital, only two bleeding
complications for which admittance to the ward was indicated, have been
documented in a recent series of about 1000 liver biopsies mainly performed in
patients with viral and autoimmune-type hepatitis.