Treatment for Non-Alcoholic Fatty Liver With Different Doses of Vitamin E

This is an interventional basic science trial for Fatty Liver focused on measuring Fatty Liver, Alpha-Tocopherol, Vitamin E, Non-Alcoholic Steatohepatitis Read More

• INCLUSION CRITERIA:

Clinical suspicion of NAFLD, defined by 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 enrollment.
• 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:

  • Abdominal obesity, defined as waist circumference > 102 cm for men or > 88 cm for women
  • Elevated triglycerides (> 150 mg/dL) or the use of medication to lower triglycerides
  • Reduced HDL cholesterol (< 40 mg/DL for men or < 50 mg/dL for women)
  • Elevated blood pressure (> 135/80 mmHg) or use of medication for hypertension

  • 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.
• Estimated average alcohol consumption < 30 g/d for men or < 20 g/d for women in the 6 months prior to enrollment and no binge-drinking behavior.
• Age > 18 years at enrollment
• Willingness to participate in the study

EXCLUSION CRITERIA:

• 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 who are inactive carriers of HBV (HBV DNA < 1000 copies/mL, HBeAg negative, Anti HDV negative) for at least 12 months prior to enrollment are also eligible. Patients receiving antiviral therapy are ineligible.
• Concomitant liver disease such as autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson s disease, alpha-1 antitrypsin deficiency.
• Presence of definite or probable drug-induced liver injury. In the case of lipid-lowering, anti-hypertensive or anti-diabetic medications that are suspected to cause elevation of aminotransferases, patients will be eligible if treatment is associated with stable enzyme levels for at least 6 months and inclusion criteria 1a. and 1c. are both present.
• Treatment with medications known to cause fatty liver disease such as atypical neuroleptics, tetracycline, methotrexate or tamoxifen
• Uncontrolled hypo- or hyperthyroidism.
• Decompensated advanced liver disease, defined as direct bilirubin > 0.5 g/dL, PT > 18, albumin < 3 g/dL, or history of ascites, encephalopathy, variceal bleeding, spontaneous bacterial peritonitis or liver transplant.
• Active coronary artery disease, defined as persistent angina pectoris, reversible ischemia on cardiac stress test or imaging, or the presence of significant coronary artery disease on imaging or catheterization. Patients with coronary artery disease that was treated by angioplasty or bypass surgery may be eligible if they have no evidence of active disease >= 1 year after intervention, can safely stop antiplatelet and anticoagulant medications before the performance of invasive procedures, and have adequate ventricular function as assessed by echocardiography or cardiology consultation. These patients will require cardiology consultation and clearance prior to enrollment.
• Congestive heart failure.
• Chronic kidney disease, with creatinine clearance < 60 ml/h.
• Uncontrolled diabetes mellitus. Patients may be enrolled if they have been on stable therapy with any anti-diabetic agent for at least 3 months prior to enrollment, are not foreseen by the physician treating their diabetes to require antidiabetic medication or dose changes during the trial and have an HbA1c <= 7.5% on enrollment.
• Treatment with vitamin E. Patients who are currently taking vitamin E as a supplement will be requested to stop for at least 3 months before becoming eligible for enrollment. Patients who are taking vitamin E for a medical indication other than NAFLD will not be eligible.
• Contraindication to or inability to undergo a liver biopsy.
• Patients who had a liver biopsy performed <= 2 years before enrollment, unless they are willing to undergo all of the trial biopsies, knowing that these biopsies are purely for research and are not clinically indicated. This will be clearly documented in the patients charts prior to enrollment.
• Patients with coagulopathy (PT/PTT values that are prolonged >= 3 seconds from the upper limit of the normal, including treatment with oral and parenteral anticoagulants), thrombocytopenia (<70,000), or platelet dysfunction will not be enrolled because of potential increase in risk of bleeding with vitamin E treatment. Antiplatelet agents taken for cardiovascular prevention will not exclude patients, unless they cannot be stopped safely for the performance of a liver biopsy.
• Maldigestion or malabsorption that can interfere with absorption of vitamin E including: steatorrhea of all causes, chronic pancreatitis, cystic fibrosis, short bowel syndrome, severe cholestasis, orlistat treatment and similar conditions
• Inability to swallow vitamin E capsules
• Allergy to vitamin E
• Alcohol or substance abuse within the past 12 months. Patients will be required to have an AUDIT score of 7 or less18, and drink no more than 14 drinks/week (for men) or 7 drinks/week (for women).
• For women of childbearing age, pregnancy or inability (or unwillingness) to practice contraception for the duration of the study or breast feeding.
• Inability to understand and give informed consent for participation.