Evaluation of the CAP-value for quantitating liver steatosis using 1H-MRS and liver biopsy as reference standard

Hepatic steatosis is becoming a large health burden in both Western and
non-Western societies. There is a need for specific diagnostic tools that can
both separate patients with significant steatosis from those without and
quantify the amount of steatosis. Quantification will help clinicians to guide
therapy. Several tools exist, such as ultrasonography, CT, serum test panels,
MR Imaging, 1H-MR Spectroscopy and liver biopsy. However, all suffer from
shortcomings. A new tool for quantifying steatosis is the Controlled
Attenuation Parameter (CAP), available on the FibroScan© (a device used to
determine the presence of liver fibrosis with ultrasound waves and vibrations).
This tool gives a continuous outcome measure and has thus far been evaluated
mainly against semi-quantitative scoring of liver biopsies and not against
other continuous outcome measures such as 1H-MR Spectroscopy or MRI based liver
fat-maps. We hypothesize that CAP-values correlate with fat percentages found
at 1H-MR Spectroscopy and that CAP-values can be used in daily practice for
reproducible and accurate fat measurements.

Main objective: investigate the correlation between CAP-values with fat
percentages found at 1H-MR Spectroscopy and steatosis grade at liver biopsy.
Secondary objectives: investigate the reproducibility of CAP-measurements;
investigate the correlation between FibroScan (CAP-value and TE-value) and MR
Elastography (Viscosity and Elastography parameters); investigate the
correlation between CAP-values and fat percentage at MRI-based liver fatmaps;
investigate and compare the burden of and patient preference for liver biopsy,
CAP-measurement and MRI-scan for liver fat measurements; investigate the
influence of a fatty meal on CAP-values in healthy volunteers.

Multi-centre observational study

Participating in this study leads to no immediate advantage for the individual
participant. However, it is important to evaluate the precision of this new
technique (CAP-value) when it is to be used in clinical practise. In the
future, patients 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. FibroScan© sessions will
take approximately 10 minutes, depending on whether one or two examiners are
present. 1H-MR Spectroscopy and MRE will be performed during one or two MRI
sessions of approximately 30-45 minutes. MRI is a non-invasive, non-ionizing
examination and has no physical burden, except that during scanning the patient
will have to lie still on his or her back in a tunnel. Subjects will have to
hold their breaths several times on expiration. Subjects can indicate when they
are ready for the next breath hold. From experience, they do not find it hard
to follow and perform these instructions. The vibrations of the MRE transducer
are felt, but do not cause discomfort or pain. Each scanning session will
require an extra visit (maximum of two) to the hospital. No oral or intravenous
contrast medium will be given to the patient. Subjects with contra-indications
for MRI-scanning are excluded from participation in this study (see appendix
E4). Subjects are not delayed in treatment for their disease as those requiring
as those requiring (change in) medication following the result of liver biopsy
are excluded. Administration of the Calogen Neutral (dietary supplement drink)
to subjects in cohort B will temporarily raise subjects* triglycerides, but
will have no temporary or lasting ill effects on subjects* health.
Additionally, 7 * 10ml blood will be drawn via venepuncture in cohort B only.
All subjects will be asked to fast overnight or for at least 8 hours before
measurements.