Growth Hormone Releasing Hormone Analog to Improve Nonalcoholic Fatty Liver Disease and Associated Cardiovascular Risk

Inclusion Criteria:

1. Men and women 18-65yo
2. Body mass index (BMI) ≥ 30kg/m2, or, for participants with known steatohepatitis, BMI ≥ 25kg/m2
3. Hepatic steatosis as demonstrated by either a) Grade 1+ steatosis on a liver biopsy performed within 12 months of the baseline visit, without >10% reduction in body weight or addition of medications to treat fatty liver, or b) liver fat fraction ≥5% on hydrogen-magnetic resonance spectroscopy (1H-MRS)
4. Hepatitis C antibody and Hepatitis B surface antigen negative. Subjects without known history of Hepatitis C or Hepatitis C treatment who have a positive Hepatitis C antibody but a negative hepatitis C viral load will also be eligible.
5. For females ≥50yo, negative mammogram within 1 year of baseline
6. If use of vitamin E ≥400 international units daily, stable dose for ≥6 mos
7. Up to date with colon cancer screening recommended by the participant's primary care physician, using whatever methodology the primary physician recommends. This will be ascertained by self-report. (If a participant does not have a primary care physician, we will discuss that colon cancer screening is recommended, typically starting at age 50y, and refer the participant to primary care through Partners if s/he desires.)

Exclusion Criteria:

1. Heavy alcohol use defined as consumption of > 20 grams daily for women or > 30 grans daily for men for at least 3 consecutive months over the past 5 years assessed using the Lifetime Drinking History Questionnaire
2. Known diagnosis of diabetes, use of any anti-diabetic medications (including thiazolidinediones or metformin), fasting glucose >126mg/dL, or hemoglobin A1c (HbA1c) ≥6.5%. Participants with stable use of metformin ≥6 months will be permitted if it is being used for pre-diabetes or another non-diabetes indication (e.g., PCOS).
3. Use of any specific pharmacological treatments for NAFLD/nonalcoholic steatohepatitis except vitamin E
4. Known cirrhosis, Child-Pugh score ≥7, stage 4 fibrosis on biopsy, or clinical evidence of cirrhosis or portal hypertension on imaging or exam. If a subject is not known to be cirrhotic at screen but is found to be cirrhotic based on the results of liver biopsy at baseline, this subject will be referred to a hepatologist for clinical care and will be excluded from further participation in the study.
5. Chronic systemic corticosteroid use in the ≤6 months prior to the baseline visit
6. Chronic use of Actigall, methotrexate, amiodarone, or tamoxifen
7. Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis
8. Use of growth hormone or growth hormone releasing hormone within the past 6 months
9. Change in lipid lowering or anti-hypertensive regimen within 2 months of screening
10. Hemoglobin < 10.0 g/dL or Creatinine >1.5mg/dL
11. Active malignancy
12. For men, history of prostate cancer or evidence of prostate malignancy by prostate specific antigen (PSA) > 5 ng/mL
13. Severe chronic illness judged by the investigator to present a contraindication to participation
14. History of hypopituitarism, head irradiation or any other condition known to affect the GH axis
15. Use of physiologic testosterone (men) or estrogen or progesterone (women) unless stable use for a year or more prior to study entry
16. Routine magnetic resonance imaging (MRI) exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip
17. Weight loss surgery within 1 year before baseline. Weight loss surgery more than 1 year prior to baseline visit is permissible as long as no active weight loss (<10% decrease in weight over past 6 months)
18. For women, positive urine pregnancy test (hCG), trying to achieve pregnancy, or breastfeeding
19. For women able to become pregnant, unwillingness to use an acceptable form of birth control during the study.
20. Known hypersensitivity to tesamorelin or mannitol
21. Contraindication to receiving beta-blocker or nitroglycerin (which are part of the coronary angiography)
22. Significant radiation exposure, including any history of radiation therapy, or any of the following in the 12 months prior to randomization: a) more than 2 percutaneous coronary interventions; b) more than 2 myocardial perfusion studies; 3) more than 2 computed tomography angiograms
23. Active consideration for a procedure or treatment that involves significant radiation exposure as defined above in the 12 months following randomization
24. Not willing or able to adhere to dose schedules and required procedures per protocol
25. Judged by the investigator to be inappropriate for the study for other reasons not detailed above.