SMART Diets for MASLD

Metabolic-dysfunction associated steatotic liver disease is defined as the presence of abnormal hepatic stored triglycerides (hepatic steatosis), with one or more of 5 cardiometabolic factors (increased body mass index or waist circumference, hyperglycemia, hypertriglyceridemia, or low HDL) and no other chronic liver disease. Pediatric hepatic steatosis is central to long-term metabolic and cardiovascular health because of the relation of hepatic steatosis to the development of other major diseases. Hepatic steatosis limits the normal metabolic role of insulin and plays a key role in the future development of the metabolic syndrome, and is the strongest predictor for the development of type 2 diabetes.

Inclusion criteria

• Children 11 to 17-years-old at the time of consenting
• Hepatic Steatosis by MRI greater than or equal to 8% on baseline MRI
• At least 1 of the following cardiometabolic risk factors: BMI greater than or equal to 85th percentile for age/sex or WC greater than 95th percentile, Abnormal cholesterol or triglyceride levels, Blood pressure BP greater than or equal to 95th percentile OR greater than or equal to 130/80 and/or signs of insulin resistance (Acanthosis Nigricans OR HOMA-IR of greater 2.0 and greater 2.6 in prepubertal and pubertal children, respectively, Fasting Insulin Level of 10 pIU/mL in prepubertal children and of 17 pIU/mL and 13 pIU/mL in pubertal girls and boys, respectively, OR Prediabetes)
• ALT greater than or equal to 40 U/L
• Currently consumes greater than or equal to 2 eight-ounce sugar drinks (or juice) per week.
• Patients of childbearing potential agrees to use adequate one or more effective methods of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Patients who are taking medications that can affect insulin (e.g., metformin, corticosteroids), most be on a stable dosage for at least 3 months prior to enrollment of the trial.
• Written informed consent from parent or legal guardian, assent from child.

Exclusion criteria

• Patients with Diagnosed Type 2 or Type 1 Diabetes Mellitus (T2DM) or HbA1c of >6.5 mg/dL at baseline
• Patients diagnosed with or suspected to have a chronic liver disease other than MASLD by screening labs or evaluation (i.e autoimmune, viral). Screening labs are defined as: Hepatitis B surface antigen, Hepatitis C virus total antibody, IgG, ceruloplasmin, and alpha 1 antitrypsin phenotype.
• Patients unable to complete MRI or Labs required for the study.
• Current participation in another clinical trial
• Current participation in a weight loss program or obesity treatment program or clinic
• Cancer or history of cancer within 5 years
• Severe illness that required hospitalization in the last 60 days
• Use of medications known to cause liver steatosis (TPN, amiodarone, chronic oral steroids, etc.)
• Patients with implanted metal devices that are not compatible with magnetic resonance imaging (MRI).
• Intellectual disability or major psychiatric disorder limiting informed assent
• Clinical evidence of cirrhosis or advanced liver disease by any one of the following abnormal labs: (Hemoglobin less than 10 g/dL, White blood cell less than 3,500 cells/mm, Neutrophil count less than 1,500 cells/mm3 of blood, Platelets less than 130,000 cells/mm3 of blood, Direct bilirubin greater than 1.0 mg/dL)
• Elevated total bilirubin except if known to have Gilbert's syndrome and direct bilirubin in normal range.
• Albumin less than 3.2 g/dL
• A history of international normalized ratio (INR) greater than 1.4
• AST or ALT greater than 250 IU/dL.
• Compensated or decompensated cirrhosis with evidence of portal hypertension.
• Patients is pregnant or breastfeeding.
• Patients who have been enrolled in a recent clinical trial and had the last dose of investigational product within 30 days or 5 half-lives of the study drug, whichever is longer.