Elucidating Growth Hormone Dynamics at Stages of Progressive Nonalcoholic Fatty Liver Disease

The purpose of this study is to investigate relationships between the body's growth hormone "axis" and nonalcoholic fatty liver disease. The growth hormone "axis" includes the hormones growth hormone and insulin-like growth factor 1, and associated proteins. We hypothesize that there will be a relationship such that people with more advanced nonalcoholic fatty liver disease will have greater impairments in the growth hormone axis. There are no treatments associated with this research study.

Several lines of existing research implicate activity of the GH/IGF-1 axis in the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in humans. Careful phenotyping of GH dynamics in individuals with NAFLD and NASH is required for comprehensive understanding of the degree to which perturbations in the GH axis contribute to the pathogenesis of NAFLD/NASH. The purpose of this research is to comprehensively assess GH dynamics in individuals across the spectrum of NAFLD to determine associations between the GH/IGF-1 axis and stages of disease progression in NAFLD.

Eligibility Criteria:
Inclusion criteria:

Men 18-70yo

* BMI between 25kg/m2 - 40kg/m2.
* Hepatitis C antibody and Hepatitis B surface antigen negative.
* Meet inclusion criteria for one of Groups 1-3 based on medical history, laboratory criteria, and hepatic fat fraction (1H-MRS) and/or liver biopsy

  * Group 1: No NAFLD: no history of NAFLD/NASH, hepatic fat fraction \<5% on 1H-MRS, ALT \< 30 U/L.
  * Group 2: Simple Steatosis: no history of NASH, hepatic fat fraction ≥10% on 1H-MRS, ALT \< 30 U/L.
  * Group 3: Nonalcoholic Steatohepatitis: Biopsy confirmed NASH within the year prior to study participation, with liver fibrosis stage 2 or 3 on biopsy.

Exclusion criteria:

* Heavy alcohol use defined as consumption of \> 30mg daily for at least 3 consecutive months over the past 5 years
* Type 1 diabetes, any use of insulin, or any use of other anti-diabetes medication except metformin or sulfonylurea. Individuals with Type 2 diabetes that is controlled by diet or by metformin and/or sulfonylurea will be eligible.
* Use of any specific pharmacological treatments for NAFLD/NASH except vitamin E within the 3 months before screening visit.
* Chronic systemic corticosteroid use in the ≤6 months prior to the baseline visit.
* Chronic use of Actigall, methotrexate, amiodarone, or tamoxifen
* Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis
* Use of GH or GHRH within the past 6 months
* Change in lipid lowering or anti-hypertensive regimen within 2 months of screening
* Hemoglobin \< 12.5 g/dL
* Severe chronic illness judged by the investigator to present a contraindication to participation
* History of hypopituitarism, head irradiation or any other condition known to affect the GH axis.
* Use of testosterone or estrogen or progesterone unless physiologic stable testosterone use for at least 1 year prior to study entry
* Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip
* Weight loss surgery within 1 year before baseline. Weight loss surgery more than 1 year prior to baseline visit is permissible if no active weight loss (\<10% decrease in weight over past 6 months)
* Lack of fluency in English and/or inability to complete the consent process in English.
* Judge by the investigator to be inappropriate for the study for other reasons not detailed above.