Improvement in non-alcoholic fatty liver disease severity is associated with a reduction in carotid intima-media thickness progression. (March 2016)

• Record Type: Journal Article
• Authors: Bhatia, Lokpal; Scorletti, Eleonora; Curzen, Nicholas; Clough, Geraldine F.; Calder, Philip C.; Byrne, Christopher D.
• Is Part Of: Atherosclerosis. Volume 246(2016)
• Page Start: 13
• Page End: 20
• Publication Date: 2016-03
• Subjects: Carotid intima-media thickness -- Non-alcoholic fatty liver disease -- Fatty acids -- Omega-3 -- Cardiovascular disease -- Atherosclerosis; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.12.028
• Languages: English
• ISSNs: 0021-9150

Abstract

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. Highlights: We studied the effects of high-dose n-3 PUFA vs placebo on CIMT progression over 18 months. We also analysed the association between biomarkers of NAFLD severity and CIMT progression. No significant effect of n-3 PUFA vs placebo on altering CIMT progression. Reduced CIMT progression was independently associated with decreased liver fat and reduced CK-18 levels over 18 months.