Postprandial FGF-19 response after fat challenge in patients with cholestatic liver disease

PBC and PSC are disorders of unknown etiology. The protective effect of FGF-19
on the liver might be lacking or insufficient in these diseases. A suboptimal
production of FGF-19 could be the cause of insufficient suppression of bile
acid synthesis in the liver, which is particularly harmfull in cholestasis,
like in PSC and PBC. With this research we want to study the intestinal
production of FGF-19 in patients with PBC and PSC after a standardized oral fat
challenge. Moreover, we will analyze the effect of this FGF19 production on
bile acid synthesis in the liver.

Hypothetically, in patients with PBC or PSC the FGF-19 production or -response
could be altered. The goal of this research is to study the FGF19 production
after a standardized oral fat challenge and the effect of this FGF19 production
on bile acid synthesis in the liver, in patients with PBC or PSC.
We postulate that PBC or PSC are the result of insufficient intestinal
FGF19-production or hepatic resistance to FGF19.

Study design: Observational study with invasive measurements.

Patients with PSC, PBC, IBD without PSC or PBC and healthy volunteers (n=12 per
group) will be invited to participate in our study. These patients will be
recruted from the Hepatology outpatient clinic of the AMC (PSC, PBC) or from
the Inflammatory Bowel Disease outpatient clinic of the AMC (IBD without PSC or
PBC). Only patients will be included with an established diagnosis via liver
biopsy (PBC), MRI (PSC) or by a clinicians judgement based on medical history,
colonoscopy and laboratory findings (IBD). Diagnostics will not be part of this
study.

To include patients in our study from the outpatient clinics, collaborating
physicians will be informed about this study and will be asked to provide
information about this study to patients that could be potential participants.
Naturally, it will be stated that the information is provided free of
obligations and that refusing the request of participation in this study does
not have any consequences for their treatment in the AMC.
Healthy subjects will be recruited from the public squares in the AMC via a
written announcement. If this will not lead to recruitment of enough subjects,
placing an advertisement in a local newspaper will be considered.

Participants in this study will be administered a standardised oral fat
challenge: 30 gram fat per square meter body surface, in the form of cream
containing 35 gram fat/100 ml.
Blood sampling will be performed at hourly intervals until 8 hours after the
oral fat challenge (8 a.m. until 4p.m.) and will be drawn from an indwelling
venous cannula that is placed for this purpose. The blood samples will be
analysed for FGF19 and C4 (precursor of bile acid synthesis) in our laboratory.
The results of these tests will not have clinical consequences for the subjects
since this is a pilot study.

Patients are expected to fast overnight (no food after 0.00 hrs a.m) until 4
p.m. on the day of the study. This means they are not allowed to eat nor drink,
except from drinking water. A standardized oral fat challenge (30 gram fat per
square meter body surface, in the form of cream containing 35 gram fat/100 ml)
will be administered. Blood sampling will be performed at hourly intervals
until 8 hours after the oral fat challenge (08.00-16.00) via an indwelling
venous cannula. The risks of this study are related to the use of this
indwelling canula during the 8 hours of the study; hematoma, recurring
haemorrhage and phlebitis might occur.