Assess hepatotoxicity of long-term azathioprine and 6-mercaptopurine use in IBD-patients as compared with a cohort of long-term 6TG users
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is histological assessed NRH
Secondary outcome
- liver stiffness assesed by Fibroscan (if available)
- endosonographically determined liver and spleen size and liver appearance
- Standard laboratory tests, including liver tests and full blood count.
Background summary
Hepatotoxicity during thiopurine therapy, of which the pathogenesis has not
completely been elucidated, is a well-known adverse event that frequently
results in thiopurine withdrawal. 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). 6-TG has been proposed
to function as a rescue drug in case of intolerance to the other
immunomodulators. However, the occurrence of NRH led to rejection of 6-TG. Not
only with 6-TG but also with classical thiopurine therapy has NRH been
described, albeit less frequent. It is likely that during AZA and 6-MP therapy
NRH is more frequent present as NRH initially does not go together with
clinical symptoms. However, studies as performed with 6-TG on the incidence and
prevalence of NRH during AZA and 6-MP are scarce. As thiopurines are being
prescribed for longer periods, there is a compelling need for long term safety
data. Furthermore, more adequate dosed 6-TG may not be so strongly related with
histological abnormalities of the liver as compared with the classical
thiopurines.
Study objective
Assess hepatotoxicity of long-term azathioprine and 6-mercaptopurine use in
IBD-patients as compared with a cohort of long-term 6TG users
Study design
This study will be a multi-center observational cross-sectional case-control
study. Each study subject will visit the hospital once within the scope of this
study. This study ends when the number of included participants reaches the
calculated number.
Study burden and risks
The patients will be asked to visit the hospital for one day. They will undergo
a Fibroscan (not in every participating hospital) and an ultrasonography of the
spleen and liver and subsequently a liver biopsy will be performed. (1.0% major
complication) Blood will be drawn by one venous puncture, physical examination
will be performed and a questionnaire will be conducted.
The benefit of participation is that liverbiopsies could reveal histological
abnormalities which require dose adjustments of the thiopurine therapy and
thereby reduce the worsening of the liver abnormalities. Also knowlegde on this
topic is of major importance for future thiopurine prescriptions in IBD
patients.
De Boelelaan 1118
Amsterdam 1081HZ
NL
De Boelelaan 1118
Amsterdam 1081HZ
NL
Listed location countries
Age
Inclusion criteria
Crohns disease or ulcerative colitis; age between 18 and 70 years; AZA , 6-MP
or 6-TG therapy for more than five years succesively; written informed consent
Exclusion criteria
anaemia (Hb<6.5mmol/l), thrombopenia (<50x10*9/l), contra-indications to
undergo a liver biopsy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL23867.029.08 |