Evaluation of the CAP-value for quantitating liver steatosis in obese children using 1H-MRS as reference standard

The number of overweight childeren in The Netherlands is growing rapidly,
causing a rise in the number of children with fatty livers. However, not all
overweight children will develop fatty livers. Currently, there are no easy,
cheap and non-invasive methods to establish which child does and which child
does not have fatty liver disease. As fatty liver disease (or hepatic
steatosis) is toxic for the liver and increases the risk of developing type 2
diabetes and cardiovascular disease, such easy, cheap and non-invasive methods
are subject of many investigations.

The current best practice for establishing the presence of fatty liver disease
is liver biopsy, which is seldomly performed in the paediatric population due
to its concomitant risks (bleeding, pain, morbididty and even mortality). Our
center (AMC Amsterdam) has ample experience with MRI-methods that allow
measurement of the liver fat percentage in either children of adults. MRI-scans
are much more patient friendly than liver biopsy but still not all subjects are
capable of having MRI-scan (they may be claustrophobic, or too large to fit the
MRI-scanner). Furthermore, the costs of MRI-scans makes this less attractive as
screening tool for the presence of fatty liver disease.

In this study we aim to investigate a new method for liver fat assessment in
(overweight) children at risk of developing fatty liver disease. This method
uses the FibroScan® devive (a special ultrasonography device that hitherto only
measured liver elasticity) to measure the CAP-value. It takes about 5 minutes,
is easy and does not cause discomfort to the patient. The CAP-value is a
quantitative measure of the amount of liver fat. In this study we will
investigate the reliability and accuracy of the CAP-value by comparing its
results with the liver fat percentage as measured with MRI. As US is still the
mainstay tool for most paediatricians and (paediatric) radiologists, a
head-to-head comparison of the performance of US and FibroScan/CAP with 1H-MRS
as reference is important and also a secondary outcome measure.

To investigate the correlation between the CAP-value measured with the
FibroScan® device and liver fat percentage measured with 1H-MRS in a
well-characterized cohort of obese children at risk of having fatty liver
disease.

An observational study in 60 patients recruited from the department of
Paediatrics of the AMC, Slotervaartziekenhuis, VUmc, Onze Lieve Vrouwe Gasthuis
and Ziekenhuis Amstelland) with an increased risk of having fatty livers. All
60 subjects will receive a FibroScan® /CAP-measurement, US and MRI-scan (1H-MR
Spectroscopy, liver fatmapping, MRE) for liver fat percentage on 1 day
performed in a single centre (AMC). By comparing both results, we will test
whether CAP-value can be used in clinical practice as a quantitative liver fat
measurement in children.

The advantage of participation in this study for patients is that presence of
liver steatosis is very accurately determined by 1H MRS. Liver steatosis is a
well established risk factor in obesity related to increased risk for diabetes
type 2. It thus helps in risk stratifying in obesity. In addition, the results
of the extended MRI scan and FibroScan®/CAP are discussed in detail with the
parents/patients by the consulting paediatrician. Furthermore, it is important
to evaluate this new technique (CAP-value) to ascertain whether it already can
be used for obese children in clinical practise. In the future, obese children
and children with chronic liver disease may benefit considerably by this new
diagnostic modality.

FibroScan® is a rapid, non-invasive measurement using a hand-held ultrasound
device that sends a vibration into the tissue of interest, in this case the
liver. It is a safe tool and the vibration causes no discomfort. The transient
elastography (TE) value gives information on liver stiffness (fibrosis) while
the new CAP-value provides information on the amount of fat. FibroScan®/CAP and
US sessions will take approximately 10 minutes (3 complete measurements). 1H-MR
Spectroscopy , liver fatmapping and MRE (for liver stiffness measurements) will
require a total in-room time of at most 30 minutes. MRI is a non-invasive,
non-ionizing examination. During scanning the patient will have to lie still on
his or her back in a tunnel. Subjects will also have to hold their breaths
several times on expiration. From experience, they do not find it hard to
follow and perform these instructions. In fact, we expect that children will
find the MRI-scans less boring when performed with breath hold procedures as
they report that lying still during MRI-scans is the most bothersome aspect of
having MRI performed.

The vibrations of the MRE transducer are felt, but do not cause discomfort or
pain. The physical burden of this examination is therefore very limited.
Participation in the study will require one extra visit to the hospital. No
oral or intravenous contrast medium will be given to the subjects. Subjects
with contra-indications for MRI-scanning are excluded from participation in
this study (see appendix E4). There will be little extra physical and
psychological discomfort associated with participation besides the four hour
fast period.