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

Abstract

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.

• Authors: Lokpal Bhatia, Eleonora Scorletti, Nicholas Curzen, Geraldine F Clough, Philip C Calder, Christopher D Byrne
• Journal: Atherosclerosis (Atherosclerosis) Vol. 246 Pg. 13-20 (Mar 2016) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 26748347 (Publication Type: Clinical Trial, Phase IV, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

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

Topics

• Adult
• Biomarkers (blood)
• Carotid Arteries (diagnostic imaging, drug effects)
• Carotid Artery Diseases (diagnostic imaging, etiology, 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, complications, diagnosis, drug therapy)
• Predictive Value of Tests
• Severity of Illness Index
• Time Factors
• Treatment Outcome
• Ultrasonography, Doppler, Duplex