Vitamin E and DHA-EE on NAFLD - Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Trial (PUVENAFLD)

Inclusion Criteria

• Male or female gender
• ≥18 years of age
• A new diagnosis or reconfirmation of previously known fatty liver by imaging (ultrasound or CT or MRI), or by liver biopsy within ≤ 4 years
• Fibroscan CAP score >300db
• Hepatic fat fraction ≥12% by MRI PDFF
• ALT≥ 40 U/L
• eGFR/Creatinine Clearance ≥ 60ml/min
• Participants with previously diagnosed Type 2 diabetes (up to 50% of sample): they must either be taking anti-diabetic medications, or their fasting (>10 hours) glucose must be ≥ 100 mg/dL at the time of screening
• Stable weight (±5%) for at least 3 months
• Subjects willing and able to give written informed consent and to understand, to participant and to comply with the clinical study requirements.

Exclusion Criteria

• Evidence of alternative causes of hepatic steatosis or other forms of chronic liver disease, e.g. Hep.B, Hep.C
• Evidence of acute Hepatitis A
• Serum ALT or AST ≥ 250 U/L
• Serum Alkaline Phosphatase > 2 ULN
• Total bilirubin > 2 ULN in the absence of Gilbert's Syndrome [In patients with Gilbert's Syndrome, direct bilirubin must not exceed 2 ULN]
• HbA1c≥9.5%
• Decompensated acute or chronic liver disease
• Clinical, imaging or histological evidence of cirrhosis
• Use of anti-NASH drugs (e.g. thiazolidinediones) in the 3 months prior to randomization
• Use of a non-stable dose of statins or fibrates in the 3 months prior to randomization
• Use of fish oil, algal oil or Krill oil supplements, drugs or foods fortified with omega-3s in the 2 months prior to randomization (>200mg DHA/d and/or >60mg EPA/d by FFQ)
• Known intolerance to vitamin E or DHA
• Malabsorption of Vit E (e.g. due to steatorrhea, chronic pancreatitis, severe cholestasis)
• Vitamin E supplementation of greater than 100 IU/day in the 3 months prior to randomization
• History of bariatric surgery (jejunoileal bypass or gastric weight loss surgery) or currently undergoing evaluation for bariatric surgery
• History of biliary diversion
• Known positivity for antibody to Human Immunodeficiency Virus (HIV)
• Patients with coagulopathy (PT ≥3 sec.from ULN), thrombocytopenia ( 21 drinks (1 drink= 12 oz regular beer, or 5 oz wine, or 1.5 oz distilled spirits) per week in men and > 14 drinks per week in women as per subject self-report as part of medical history.
• Active substance abuse, such as oral, inhaled or injected illicit drugs (except marijuana), in the year prior to screening
• Women of childbearing potential: positive pregnancy test during screening or at randomization or unwillingness to use an effective form of birth control during the trial
• Women who are breastfeeding
• Any other condition which, in the opinion of the investigator would impede compliance or hinder completion of the study
• Subjects who are enrolled in an interventional clinical study or have received an investigational new drug or product within the last 30 days prior to screening
• Participants diagnosed with type 1 diabetes