Effect of Fish-oil on Non-alcoholic Steatohepatitis (NASH)
Condition: Non-alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine the effect of Omega-3 Fish oil supplementation on
      hepatic gene expression in patients with Non Alcoholic Steatohepatitis (NASH). In addition,
      effects of fish oil on intestinal microbiota will be assessed.
    

Detailed description: 
      Changes in fatty acid (FA) composition within the liver may influence lipid metabolism and
      inflammation. This is poorly understood in humans.

      Especially omega-3 FA are important: They promote FA oxidation over storage and are important
      for export of lipids from the liver. Omega-3 FA have also anti-inflammatory properties.

      Changes in liver FA composition may be influenced by dietary intake, high rate of lipid
      peroxidation (LP) or low delta-6 desaturase enzyme activity. We and others recently showed
      that NASH patients had lower hepatic n-3 and n-6 polyunsaturated FA (PUFA) with increased
      lipid peroxidation and low antioxidant status when compared to patients with minimal findings
      on liver biopsy. The dietary intake of FA was similar among the 3 groups suggesting that the
      difference in hepatic FA composition may be related to high lipid peroxidation or low delta-6
      desaturase activity. This difference in hepatic FA composition may be of significance in the
      pathogenesis of NASH since it may change gene expressions in regard to lipid metabolism.

      This pilot study in NASH to assess the effect of n-3 PUFA supplementation on FA composition
      (liver and red blood cells), hepatic gene expression, and histology. We will also assess the
      ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver and red blood
      cells (RBC). Oxidative stress, insulin resistance and nutritional measurements will be
      performed to further characterize these patients.

      New research suggests that the composition of the gut flora (intestinal microbiota) may play
      a role in the development of NASH. The effect of fish oil on the intestinal microbiota has
      not been examined in humans. Therefore, intestinal microbiota is also measured before and
      after intervention and associations between changes in microbiota and changes in liver
      histology will be examined. In addition, bacterial products (short chain fatty acids in
      stool, lipopolysaccharide in plasma, bacterial DNA in plasma), and plasma choline will be
      measured. An environmental questionnaire will capture factors that can influence the
      intestinal microbiota.
    

Intervention name(s): Omega-3 capsules-Fish Oil
Intervention type(s): Other
Intervention description(s): Patients will take 2 capsules (1.0 g each) of n-3 PUFA (0.82/0.44 g of EPA/DHA) daily x 12 months. Since n-3 PUFA supplementation can be a potential treatment for NASH and since BMI will be< 30 kg/m2 for all subjects, patients will be told to keep their lifestyle, diet and medication stable (unless medically necessary) for the study duration in order to minimize environmental effect on gene expression.
Other intervention name(s): Product Name: Amber 40/20 Ethyl ester (EE); 1000 mg capsules (lemon-lime flavor); Product Code: 4020PB1000CT
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: non-alcoholic fatty liver disease; non-alcoholic steatohepatitis