The natural history of Non-alcoholic Fatty Liver Disease in obese children: a long-term follow-up study.

Non-alcoholic Fatty Liver Disease (NAFLD) is defined as chronic hepatic
steatosis that is not caused by a metabolic/genetic disease, infections, use of
steatogenic drugs, alcoholic consumption or malnutrition. The spectrum of NAFLD
ranges from simple steatosis, steatohepatitis, to fibrosis and cirrhosis.
Symptoms will usually be absent until complications like decompensated
cirrhosis, liver failure or hepatocellular carcinoma occur.
In children the reported pooled prevalence of NAFLD in general population
studies is 8% and 34% in studies based on child obesity clinics. However,
advanced fibrosis is reported in up to 17% of children referred to liver
centres after screening. In view of their long life expectancy, those with
significant fibrosis at paediatric age are considered particularly at risk of
cirrhosis and its complications during their life time. NAFLD is not only a
liver disorder, but also an independent risk factor for type 2 diabetes and
probably also for cardiovascular disease and nephropathy at adult age.

The high prevalence and important long term health risks makes NAFLD highly
suitable for screening. Current guidelines differ in their advise on the
frequency of screening and the follow-up of patients. This is due to limited
data on the prevalence and progression of liver fibrosis in paediatric NAFLD
patients. Therefore guidelines are mostly based on expert opinion. An evidence
based guideline is urgently needed to identify patients with NAFLD and fibrosis
in time and thereby offer them adequate treatment and follow-up.

To investigate the natural history of NAFLD, we will determine the change in
ELF test for fibrosis and change in liver fat percentage measured by 1H-MRS.

A long term follow-up study.

MRI-scans do not involve ionizing radiation and inherent risks are therefore
low. As no intravenous contrast is used, there are no risks from
contrast-induced-nephropathy or IV-leakage. Claustrophobia can occur, but this
is unlikely given the new wide-bore 3T MR Scanner at the AMC that additionally
allow subjects to watch TV during the examination. FibroScan is a safe
ultrasound-based method to detect steatosis and fibrosis and is already used in
clinical practice. The measurement takes 5-10 minutes and is not painful.
FibroScan does not involve ionizing radiation.
As such, no structural risk analysis was performed, as the registered product
is used within its indication and inherent risks in this measurement are
considered low. Venepuncture is a safe method but can sometimes cause mild
discomfort. We conclude that participation does not form any health risk for
the subjects and that the psysical burden is minimal.
Some of the participants in this follow-up study have been identified as
suffering from NAFLD in the previous study. It is standard clinical care that
NAFLD is followed up by imaging (usually ultrasonography) and blood sampling
every 6-12 months in order to identify deterioration of liver function. By
participating in this study, steatosis can be assessed more accurately since
1H-MRS has a higher accuracy in detecting steatosis compared to
ultrasonography. In addition, participants will undergo screening for fibrosis
(ELF test and FibroScan) and will be referred to the NAFLD outpatient clinic
when signs of fibrosis are present. Subjects who did not have NAFLD at baseline
or who showed remission of NAFLD after lifestyle intervention are still at risk
of recurrence of steatosis if obesity or other risk factors are still present.
The advantage of participation for those patients is that NAFLD is accurately
detected and they will receive proper follow-up or treatment if NAFLD is indeed
present.