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 ?-coefficient 0.32, p = 0.005), reduced CK-18 levels (standardized ?-coefficient 0.22, p = 0.04) and antihypertensive usage (standardized ?-coefficient ?0.31, p = 0.009) in multivariable regression analysis after adjusting for all potential confounders. Decreased weight (standardized ?-coefficient 0.30, p < 0.001) and increased DHA tissue enrichment during the 18-month study (standardized ?-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.

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Identifiers

ORCID for L. Bhatia: orcid.org/0000-0002-7379-0686

ORCID for N. Curzen: orcid.org/0000-0001-9651-7829

ORCID for G. Clough: orcid.org/0000-0002-6226-8964

ORCID for P. Calder: orcid.org/0000-0002-6038-710X

ORCID for C. Byrne: orcid.org/0000-0001-6322-7753

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