title: Design and rationale of the WELCOME trial: A randomised, placebo controlled study to test the efficacy of purified long chainomega-3 fatty acid treatment in non-alcoholic fatty liver disease [corrected].
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) represents a range of liver conditions from simple fatty liver to progressive end stage liver disease requiring liver transplantation. NAFLD is common in the population and in certain sub groups (e.g. type 2 diabetes) up to 70% of patients may be affected. NAFLD is not only a cause of end stage liver disease and hepatocellular carcinoma, but is also an independent risk factor for type 2 diabetes and cardiovascular disease. Consequently, effective treatments for NAFLD are urgently needed.
  
  
  OBJECTIVE
  The WELCOME study is testing the hypothesis that treatment with high dose purified long chain omega-3 fatty acids will have a beneficial effect on a) liver fat percentage and b) two histologically validated algorithmically-derived biomarker scores for liver fibrosis.
  
  
  METHODS
  In a randomised double blind placebo controlled trial, 103 participants with NAFLD were randomised to 15-18months treatment with either 4g/day purified long chain omega-3 fatty acids (Omacor) or 4g/day olive oil as placebo. Erythrocyte percentage DHA and EPA enrichment (a validated proxy for hepatic enrichment) was determined by gas chromatography. Liver fat percentage was measured in three discrete liver zones by magnetic resonance spectroscopy (MRS). We also measured body fat distribution, physical activity and a range of cardiometabolic risk factors.
  
  
  METHODS
  Recruitment started in January 2010 and ended in June 2011. We identified 178 potential participants, and randomised 103 participants who met the inclusion criteria. The WELCOME study was approved by the local ethics committee (REC: 08/H0502/165; www.clinicalTrials.gov registration number NCT00760513).
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK. Electronic address: e.scorletti@soton.ac.uk.
authors.forename: E
authors.initials: E
authors.lastname: Scorletti
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: L
authors.initials: L
authors.lastname: Bhatia
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: K G
authors.initials: KG
authors.lastname: McCormick
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: G F
authors.initials: GF
authors.lastname: Clough
authors.affiliation: Hepatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: K
authors.initials: K
authors.lastname: Nash
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: P C
authors.initials: PC
authors.lastname: Calder
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Byrne
mesh_terms: D000328:Adult; D015415:Biomarkers; D001837:Body Weights and Measures; D004032:Diet; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D015444:Exercise; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D006334:Heart Function Tests; D006801:Humans; D008099:Liver / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000503:physiopathology; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000503:physiopathology; D000069463:Olive Oil; D010809:Physical Fitness; D010938:Plant Oils; D012107:Research Design; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D000069463:Olive Oil; D010938:Plant Oils; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor
keywords: DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; MRS: magnetic resonance spectroscopy; NAFLD: Non-alcoholic fatty liver disease; Purified long chain omega-3 fatty acids