Nonalcoholic fatty liver disease (NAFLD) is an obesity-associated liver disease that affects an
estimated 7 million children in the United States. It is the most common reason for liver
transplantation in adults and increases long term risk of diabetes and cardiovascular disease.
NAFLD disproportionately affects Hispanic children and is an exceptionally important health
disparity. The proposed studies will address prevention of NAFLD in children because current
treatments are only partially effective, and no cure exists for the disease. A unique physiologic
opportunity exists in children in that NAFLD appears to have a narrow time of onset in children,
during early puberty. In a recently completed randomized clinical diet provision trial comparing
a very low free sugar diet to usual care, we demonstrated improved hepatic steatosis, liver
inflammation and rate of de novo lipogenesis in children who already have NAFLD. However, it
is unknown if providing a low free sugar diet (LFSD) in pre-pubertal children can help prevent
hepatic steatosis and NAFLD onset as they age into puberty. The central study supporting the 3
aims is a 1 year randomized prevention trial with a 1 year follow-up observational study in children
who are pre-pubertal at baseline and who are known to be in a high-risk group for developing
NAFLD because of Hispanic ethnicity and a first degree relative with NAFLD or type 2 diabetes.
The intervention will replace typical drinks and food high in (non-dairy) sugars with low or no
sugar foods using our established methods including 1) provision of food for the entire family 2)
facilitated grocery shopping 3) home visits 4) behavior change counseling and, 5) frequent
monitoring. Hispanic children age 7-9 years, Tanner stage 1, who are at high risk of NAFLD by
family history will be randomized to LFSD intervention or usual care with matching for contact
hours. The primary outcome is hepatic steatosis by MRI-PDFF at 1 year. Aim 1 tests whether the
intervention protects against increase in hepatic steatosis at 1 year and NAFLD onset at 2 years.
Aim 2 tests gene variants associated with NAFLD, baseline anthropometrics and insulin
sensitivity modifiers of the impact of LFSD on change in hepatic steatosis at 1 year. Aim 3 explores
biochemical and lipid metabolism mechanisms underlying hepatic steatosis and LFSD. In
summary, this trial will generate evidence regarding the potential for using free sugar restriction
as a NAFLD prevention strategy for children at increased risk of NAFLD. The findings will have
sustained and significant implications for health promotion in Hispanic children, reduce health
disparities, and inform future prevention efforts for children at increased risk of NAFLD.