Study of Fish Oil to Reduce ALT Levels in Adolescents

Over the past two decades, pre-adult nonalcoholic fatty liver disease (NAFLD) has emerged
from the relative obscurity to become the most common cause of liver disease in pediatric
patients. Currently, over 17% of US children and adolescents have a BMI at or greater than
the 95th percentile for age and gender and 20% of children in weight management programs are
estimated to have NAFLD. Untreated NAFLD can lead to fibrosis and to established cirrhosis
in children as young as 10. Fish oils are a rich source of omega-3-acid ethyl esters or n-3
long-chain polyunsaturated fatty acids, and increasing evidence suggest they may safely
improve hepatic steatosis. Given the prevalence of obesity, of NAFLD, and the severe,
progressive nature of this condition, effective treatment strategies are urgently needed. We
plan to gather preliminary data on the efficacy and safety of fish oil supplements in
reducing persistent elevation of ALT levels and hepatic steatosis on abdominal CT-scan among
urban youth (BMI>=95th percentile). This preliminary data will provide the necessary
information to calculate the sample size for a phase 2 trial.

Inclusion Criteria:

- BMI (kg/m2) at or above the 95th percentile for age and gender

- Weight below 400 pounds (less than 182 kilograms)

- Persistent elevation of ALT (41-90 UI/L at study screening)

- Presence of hepatic steatosis on abdominal CT-scan

- Able to give informed consent/assent

Exclusion Criteria:

- Type 2 diabetes mellitus

- Prior drug treatment for diabetes, insulin insensitivity, or weight loss medications
six months before screening

- Use of prescription strength glucocorticoids within three months before screening

- History of syndrome or medical disorder associated with significant obesity

- Participation in a weight loss program within six months of screening resulting in 5%
or more weight loss

- History of weight loss surgery

- Alcohol use more than twice weekly or more than 3 alcohol containing beverages within
a 24-hour period in the past six months

- Known or suspected bleeding condition

- History of liver disease including prior liver biopsy with NASH type 2 or cirrhosis

- Former or present positive blood tests for Infectious hepatitis B or C, autoimmune
hepatitis, Wilson disease, Alpha-1 anti-trypsin deficiency, Iron storage disease, or
high TSH

- History of past or current pregnancy

- Use of illegal/illicit drugs

- Other conditions contraindicated or cause for caution in the use of fish oil

- Unable to comply with the protocol

- Any other serious disease determined by the study gastroenterologists and physician
nutrition specialist as potential study risk for the patient