title: Improvement in non-alcoholic fatty liver disease severity is associated with a reduction in carotid intima-media thickness progression.
abstract: OBJECTIVE
  n-3 polyunsaturated fatty acid (PUFA) treatment may decrease liver fat in non-alcoholic fatty liver disease (NAFLD), but uncertainty exists whether this treatment also decreases cardiovascular disease (CVD) risk in NAFLD. We tested whether 15-18 months n-3 PUFA [docosahexaenoic acid (DHA) and eicosapentaenoic acid] (Omacor/Lovaza, 4 g/day) vs placebo decreased carotid intima-media thickness (CIMT) progression, a surrogate marker of CVD risk. We also evaluated if improvement in markers of NAFLD severity was associated with decreased CIMT progression over time.
  
  
  METHODS
  In a pre-specified sub-study of the WELCOME (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy) trial (NCT00760513), CIMT was measured using B-mode ultrasound while NAFLD severity was assessed by measuring liver fat percentage (magnetic resonance spectroscopy) and hepatic necro-inflammation (serum cytokeratin-18 (CK-18) concentration), at baseline and end of study.
  
  
  RESULTS
  92 patients (age 51.5 ± 10.7 years, 57.6% men) completed the study. In the treatment group (n = 45), CIMT progressed by 0.012 mm (IQR 0.005-0.020 mm) compared to 0.015 mm (IQR 0.007-0.025 mm) in the placebo group (n = 47) (p = 0.17). Reduced CIMT progression in the entire cohort was independently associated with decreased liver fat (standardized β-coefficient 0.32, p = 0.005), reduced CK-18 levels (standardized β-coefficient 0.22, p = 0.04) and antihypertensive usage (standardized β-coefficient -0.31, p = 0.009) in multivariable regression analysis after adjusting for all potential confounders. Decreased weight (standardized β-coefficient 0.30, p < 0.001) and increased DHA tissue enrichment during the 18-month study (standardized β-coefficient -0.19, p = 0.027) were both independently associated with decreased liver fat, but not with CK-18.
  
  
  CONCLUSIONS
  Improvement in two markers of NAFLD severity is independently associated with reduced CIMT progression.
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 and University Hospital Southampton NHS Foundation Trust, Southampton, UK; Wessex Cardiac Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. Electronic address: lokebhatia@aol.com.
authors.forename: Lokpal
authors.initials: L
authors.lastname: Bhatia
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 and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Scorletti
authors.affiliation: National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK; Wessex Cardiac Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Curzen
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 and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Geraldine F
authors.initials: GF
authors.lastname: Clough
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 and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Philip 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 and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Byrne
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000187:drug effects*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000209:etiology / Q000517:prevention & control*; D059168:Carotid Intima-Media Thickness; D018450:Disease Progression; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D018616:Ultrasonography, Doppler, Duplex
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor
keywords: Atherosclerosis; Cardiovascular disease; Carotid intima-media thickness; Fatty acids; Non-alcoholic fatty liver disease; Omega-3