Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

Non-alcoholic fatty liver disease (NAFLD) is a significant health problem in obese
adolescents. Obese children and adolescents have significant reductions in growth hormone
secretion, and we hypothesize that augmenting growth hormone in this population will decrease
liver fat. Growth hormone inhibits hepatic de novo lipogenesis, which is an important source
of hepatic lipid. Patients with pituitary GH deficiency have a higher prevalence of NAFLD and
non-alcoholic steatohepatitis (NASH) than the general population, and replacement of GH in
these individuals reduces signs of liver damage. The purpose of this study is to test the
hypothesis that growth hormone treatment will decrease liver fat quantity in young adults who
begin the trial with more than 5% liver fat measured by magnetic resonance spectroscopy.

Inclusion criteria:

1. Males and Females ages 18-29yo

2. BMI ≥95th percentile and/or ≥30kg/m^2

3. Hepatic fat ≥5% by hydrogen magnetic resonance spectroscopy (1H-MRS)

4. IGF-1 standard deviation score (SDS) < 0

Exclusion criteria:

1. Alcohol consumption of >14 drinks per week (Females) or >21 drinks per week (Males)

2. Use of insulin or oral anti-diabetic medications, or hemoglobin A1c (HbA1c) >7% or
fasting glucose ≥126mg/dL

3. Use of corticosteroid, gonadal steroids, or methotrexate ≤ 3 months prior to baseline
visit

4. Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis,
or autoimmune hepatitis

5. hemoglobin < 11.0 g/dL or weight < 50kg

6. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x upper limit
of normal (ULN), total bilirubin > ULN, positive hepatitis B surface antigen (sAg), or
positive hepatitis C antibody

7. Routine magnetic resonance imaging (MRI) exclusion criteria (including weight >450
pounds)

8. Use of weight-loss medications or previous weight loss surgery

9. Pregnant or breastfeeding, or, for sexually-active females, unwillingness to use an
appropriate form of contraception during the study

10. Known cirrhosis or clinical evidence of cirrhosis or portal hypertension on imaging or
exam

11. Use of growth hormone (GH) or growth hormone releasing hormone within the past 1 year

12. Change in lipid lowering or anti-hypertensive medications within 3 months of screening

13. Change in vitamin E or ursodiol <6 months before screen; subjects on stable doses of
Vitamin E and/or Ursodiol for ≥6 months will be eligible.

14. History of malignancy or active malignancy

15. History of hypopituitarism, head irradiation or any other condition or chronic illness
known to affect the GH axis