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

Background and aims: n-3 polyunsaturated fatty acid (PUFA) treatment may decrease liver fat in nonalcoholic fatty liver disease (NAFLD), but uncertainty exists whether this treatment also decreases cardiovascular disease (CVD) risk in NAFLD. We tested whether 15e18 months n-3 PUFA [docosahexaenoic acid (DHA) and eicosapentaenoic acid] (Omacor/Lovaza, 4 g/day) vs placebo decreased carotid intimamedia 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 Bmode 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 0.005e0.020 mm) compared to 0.015 mm (IQR 0.007 e0.025 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 beta-coefficient 0.32, p = 0.005), reduced CK-18 levels (standardized beta-coefficient 0.22, p = 0.04) and antihypertensive usage (standardized beta-coefficient -0.31, p = 0.009) in multivariable regression analysis after adjusting for all potential confounders. Decreased weight (standardized beta-coefficient 0.30, p < 0.001) and increased DHA tissue enrichment during the 18-month study (standardized beta-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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.