Improvement in non-alcoholic fatty liver disease severity is associated with a reduction in carotid intima-media thickness progression

Atherosclerosis. 2016 Mar;246:13-20. doi: 10.1016/j.atherosclerosis.2015.12.028. Epub 2015 Dec 24.


Background and aims: 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.

Conclusion: Improvement in two markers of NAFLD severity is independently associated with reduced CIMT progression.

Keywords: Atherosclerosis; Cardiovascular disease; Carotid intima-media thickness; Fatty acids; Non-alcoholic fatty liver disease; Omega-3.

Publication types

  • Clinical Trial, Phase IV
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Carotid Arteries / diagnostic imaging*
  • Carotid Arteries / drug effects*
  • Carotid Artery Diseases / diagnostic imaging*
  • Carotid Artery Diseases / etiology
  • Carotid Artery Diseases / prevention & control*
  • Carotid Intima-Media Thickness*
  • Disease Progression
  • Docosahexaenoic Acids / therapeutic use*
  • Double-Blind Method
  • Drug Combinations
  • Eicosapentaenoic Acid / therapeutic use*
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / diagnosis
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Predictive Value of Tests
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Ultrasonography, Doppler, Duplex*


  • Biomarkers
  • Drug Combinations
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Omacor

Associated data