Non-Alcoholic Fatty Liver Disease in children: determining the prevalence of liver fibrosis using FibroScan®

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 at adult age. The high prevalence and
important long term health risks makes NAFLD highly suitable for screening.
Screening for NAFLD in children with obesity is propagated in all major
national and international obesity and hepatology guidelines. Screening
consists of detecting NAFLD, i.e. liver steatosis, and subsequent detecting the
presence of fibrosis, since those with fibrosis are at highest risk of liver
and non-liver morbidity and mortality. However, screening for NAFLD is not
straightforward due to several gaps of knowledge, most importantly:
- non-invasive tools to subsequently measure liver fibrosis have not been
evaluated in a screening setting
- there is limited data on the prevalence and progression of liver fibrosis in
paediatric NAFLD
- there is a lack of data on the cost-effectiveness of screening in children
Due to these gaps of knowledge, guidelines are mostly based on expert opinion
and do not provide a comprehensive algorithm on when and how to stage fibrosis.
Consequently, although screening is widely performed in clinical practice,
physicians use different primary screening tools, do not know which screening
result should prompt referral and often do not refer patients, when referred
staging for fibrosis of those with abnormal screening test is often not
performed.Therefore, at present those with relevant liver fibrosis are not
adequately identified and denied follow-up and treatment by intensified life
style intervention. The urgency to come to a more comprehensive screening
strategy is further underscored by the development of additional
pharmacological therapies for NAFLD. These therapies are likely to become
available in the near future and will make advanced NAFLD a more easily
treatable disorder.

1) determine the percentage of children with probable significant fibrosis
(F>=2) using FibroScan®, when screening children based on the NASPGHAN 2017
guideline.
2) determine the cost-effectiveness of screening for NAFLD when following the
NASPGHAN 2017 screening guideline.
3) investigate the usefulness of two additional non-invasive fibrosis tests;
- XL-probe versus M-probe of FibroScan®
- ELF-test versus FibroScan® (M-probe)
- Shear wave elastography versus FibroScan® (M-probe) and ELF test
4) Quality of life in children with NAFLD
5) Patient experience of screening process and illness perception

This is a prospective study.

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. For this
study, the FibroScan® measurement will be performed with one extra probe
(XL-probe). Therefore the measurement will take an additional 5 minutes. We
consider this as no extra burden of the participants. Shear wave elastography
is a modality that is incorporated in a regular ultrasound apparatus. This
measurement will take 5 minutes and causes no discomfort. Venepuncture is part
of standard clinical care. For this study 15 ml extra blood will be drawn
during the standard venepuncture. Therefore we conclude that there will be
little extra physical discomfort with participation.