Clinical Research Directory

* INCLUSION CRITERIA: For the entire cohort: * Male or female aged \> 18 years * Ability to provide informed consent For group 1 subjects (NAFLD) * Biopsy-proven NAFLD within 2 years prior to screening, OR * The presence of at least two of the following criteria: * Suggestion of liver fat by an imaging study (ultrasound, CT scan, MRI or MR spectroscopy) performed in the 6 months prior to screening * Elevated aminotransferase levels (ALT \> 31 U/L for men or \> 19 U/L for women, or AST \> 30 U/L) on at least two occasions in the 6 months preceding enrollment. * Presence of the metabolic syndrome, defined according to the modified AHA/NCEP criteria as the presence of at least three of: i. Abdominal obesity, defined as waist circumference \> 102 cm for men or \> 88 cm for women ii. Elevated triglycerides (\> 150 mg/dL) or the use of medication to lower triglycerides iii. Reduced HDL cholesterol (\< 40 mg/DL for men or \< 50 mg/dL for women) iv. Elevated blood pressure (\> 135/80 mmHg) or use of medication for hypertension v. Elevated fasting glucose levels (\> 100 mg/dL) or use of anti-diabetic medication For the purpose of inclusion, the presence of overt diabetes mellitus type 2 will be considered equivalent to the presence of the metabolic syndrome, even if the other criteria are absent. For group 2 subjects (non-NAFLD metabolic syndrome): * Evidence of metabolic syndrome * Normal transaminases (ALT less than or equal to 31 U/L for men or less than or equal to 19 U/L for women, or AST less than or equal to 30 U/L) at screening * Absence of liver fat by imaging or liver biopsy within 6 months of screening For group 3 subjects (healthy volunteers): * No history of known liver disease * Not on any regular systemic medications (with the exception of oral contraceptives) * BMI \<= 25 kg/m2 * Non diabetic * Normal transaminases and fasting glucose (\<95 mg/dL) EXCLUSION CRITERIA: 1. Concomitant liver disease such as autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson s disease, alpha-1 antitrypsin deficiency 2. Chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who were treated successfully for HCV and achieved sustained virological response can be eligible for enrollment \> 18 months after treatment cessation. Patients receiving antiviral therapy are ineligible. 3. Estimated average alcohol consumption \> 30 g/d for men or \> 20 g/d for women in the 6 months prior to enrollment, or binge-drinking behavior . 4. Gain or loss of \> 10% body weight within the 6 months prior to enrollment. 5. Decompensated liver cirrhosis, defined as a past or present occurrence of a decompensation event (variceal bleeding, ascites, spontaneous bacterial peritonitis, encephalopathy or hepatocellular carcinoma or by albumin \< 3 g/dl, PT \> 3 seconds above the upper limit of the norm, platelet count \< 70,000 or total bilirubin \> 2 mg/dL (in the absence of Gilbert s syndrome). 6. Pregnancy or lactation 7. Treatment with medications known to cause fatty liver disease such as atypical neuroleptics, tetracycline, methotrexate or tamoxifen 8. Disorders interfering with substrate absorption such as gastric bypass surgery, malabsorption disorders, use of orlistat or bile acid sequestrants, or extensive small bowel resection. 9. Diabetic patients requiring insulin treatment 10. Lactose intolerance or allergy to Ensure or one or more of its components 11. Hyper/hypothyroidism 12. Inability to remain sedentary for 4 hours, or to remain for 26-30 hours in the metabolic chamber 13. Inability to obtain vascular access for the required blood samples