Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the leading cause of liver disease
in children. The name of NAFLD recently changed to metabolic dysfunction associated
steatotic liver disease (MASLD). The definition of MASLD is the presence of steatosis in
the liver and a metabolic abnormality, in the setting of other liver steatotic liver
diseases having been ruled out. Due to its association with obesity and diabetes, MASLD
prevalence is rising worldwide following the upward trends of these diseases. Among the
United States pediatric population, the prevalence of NAFLD has been measured at around
11% and it varies widely among races. MASLD is likely very similar in numbers. Because of
the natural history of the disease, MASLD patients are at risk of developing
cardiovascular complications and hepatocellular carcinoma, raising the issue of
diagnosing and treating promptly with the most accurate approaches.
Liver biopsy is the gold standard for assessing inflammation and fibrosis in metabolic
dysfunction associated steatotic liver disease. This test is highly sensitive and
specific, however some weaknesses exist. Liver biopsy uses a small sample size which can
misrepresent the overall health/disease of the organ and there can be interpretation
variability within the pathologists assessing the histology. Liver biopsy is also an
invasive test, making it less desirable due to the potential of complications and cost.
Due to these and despite being the most exact test, its invasive nature and its high
price, make it not widely used.
There are several clinical needs, including a better way to rapidly diagnose MASLD in the
outpatient clinic setting and to measure the severity of MASLD in patients already
diagnosed. The first need, to diagnose MASLD requires demonstrating the presence of
steatosis through imaging and sending some standard labs to rule out other conditions and
assess metabolic features. The second need focuses primarily on fibrosis assessment,
because the amount of fibrosis is the most closely associated with long term outcomes.
While inflammation quantity is also important for staging MASLD, inflammation tends to
rise and fall with changes in lifestyle and presents a less durable finding. Currently,
in pediatrics the level of inflammatory injury is reasonably well represented by change
in alanine transaminase (ALT). Thus, validating it is not a primary or secondary
objective in this proposal.
The most accurate non-invasive imagining diagnostic test for hepatic steatosis in MASLD
is Magnetic Resonance Imagining (MRI) and Magnetic Resonance Spectroscopy (MRS).
Specifically, the MRI with Proton Density Fat Fraction (PDFF), has shown to have the best
results at diagnosing liver steatosis since it is able to map for fat to the whole liver.
Accurate fibrosis assessments have been accomplished with the use of Magnetic Resonance
Elastography (MRE) and possess an advantage over ultrasound fibrosis measurements because
it is independent of abdominal fat. In spite of that, this imaging is not widely
available, and it is still highly priced making it less available.
There are a wide variety of ultrasound based tests measuring liver steatosis and it is an
inexpensive alternative to diagnose and follow-up patients. Ultrasound is used in
conjunction with scores to measure steatosis according to liver echogenicity and
visibility of the surrounding organs. Nonetheless, the sensitivity to finding disease
decreases for mild cases and only improves when patients have more than 20% hepatocytes
that are fatty. Controlled Attenuation Parameter (CAP) in FibroScan machines has been
used to address this issue by measuring the ultrasound attenuation and propagation speed
of a shear wave delivered by an ultrasound probe (transient elastography, TE). Even
though the CAP and TE provide better results, it still has its downfalls in being
accurate when the patient is obese and not being extensively accessible.
Velacur is a liver ultrasound that measures hepatic fat and fibrosis through the
propagation of a continuously, externally conducted shear wave. Velacur will measure
hepatic steatosis and fibrosis through the measures of ultrasound attenuation and the
propagation of a shear wave through the liver to measure its stiffness but will perform
the stiffness reading using a continuous, externally conducted wave. This technology is
thought to provide a better liver volume sample, giving a better reading in obese
patients and the software gives live data for easy and fast patient follow-up, making it
easy to use from Medical Assistants to Physicians.
There is a need to validate new non-invasive tests to find accurate diagnostic and liver
disease staging tools that are simple to use, with easy access and affordable. Due to the
small size of the Velacur device and similarity to other technologies available, and the
opportunity of collecting blood biomarkers, the investigators want to study the
possibility of using both technologies in an outpatient setting to screen and follow up
pediatric population with MASLD in Atlanta, Georgia, USA. The investigators will complete
a Velacur exam and/or collect blood biomarkers on patients recruited into the study.
Statistical analysis will be performed comparing Velacur with the current gold standards
of MRI and liver biopsy.