Association of prognostic cardiovascular biomarkers with non-alcoholic fatty liver disease and effects of high-dose n-3 fatty acids treatment

Abstract

ABSTRACT
SCHOOL OF MEDICINE
Human Development & Health
Thesis for the degree of Doctor of Philosophy
Association of prognostic cardiovascular biomarkers with non-alcoholic fatty liver disease and effects of high-dose n-3 fatty acids treatment
by Lokpal Bhatia
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition affecting up to one-third of the population worldwide, associated with increased cardiovascular (CV) mortality. Little is known about how prognostic CV biomarkers may be altered in association with changes in NAFLD severity over time. Importantly, there is currently no established pharmacological treatment option for NAFLD.
The WELCOME* trial was a randomised, double-blind placebo-controlled study testing the effects of 15-18 months of high-dose n-3 fatty acids (FA; Omacor 4g/day) versus placebo in 103 NAFLD subjects to reduce liver fat percentage (measured by magnetic resonance spectroscopy). Prespecified sub-studies also investigated whether prognostic CV biomarkers (carotid intima-media thickness (CIMT) and echocardiographic markers of left ventricular (LV) diastolic function) and insulin sensitivity were related to severity of NAFLD; and also if these biomarkers improved with n-3 FAs in relation to liver fat reduction. We also measured erythrocyte docosahexaenoic acid (DHA) enrichment as a biological measure of treatment compliance.
We found that significantly increased DHA enrichment through n-3 FA supplementation over 15-18 months resulted in a significant reduction in liver fat, as well as improving hepatic insulin sensitivity. Conversely, this did not have a beneficial effect on prognostic CV biomarkers with respect to reducing CIMT progression or improving key LV diastolic function indices. However, we also described for the first time, an independent association between percentage liver fat reduction and reduced CIMT progression in the entire cohort over the duration of study. Similarly, we found an independent association between liver fat reduction over 15-18 months and an improvement in markers of LV diastolic function across the entire cohort.
In conclusion, n-3 FAs may be a viable therapeutic option for treating liver fat and improving hepatic insulin sensitivity. Reducing liver fat in NAFLD over 15-18 months was independently associated with improvements in prognostic CV biomarkers.
*WELCOME study (Wessex evaluation of fatty liver and cardiovascular markers in NAFLD with Omacor therapy; www.clinicaltrials.gov NCT00760513)

More information

Identifiers

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

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

Catalogue record

Export record