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

Improvement in non-alcoholic fatty liver disease severity is associated with a reduction in carotid intima-media thickness progression.
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 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.
carotid intima-media thickness, non-alcoholic fatty liver disease, fatty acids, omega-3, cardiovascular disease, atherosclerosis
0021-9150
13-20
Bhatia, L.
778149c5-c2d5-4e58-81ba-8a45c63056d8
Scorletti, E.
42bb0659-ac67-4a73-bf36-a881fe6c1563
Curzen, N.
70f3ea49-51b1-418f-8e56-8210aef1abf4
Clough, G.
9f19639e-a929-4976-ac35-259f9011c494
Calder, P.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Byrne, C.
1370b997-cead-4229-83a7-53301ed2a43c
Bhatia, L.
778149c5-c2d5-4e58-81ba-8a45c63056d8
Scorletti, E.
42bb0659-ac67-4a73-bf36-a881fe6c1563
Curzen, N.
70f3ea49-51b1-418f-8e56-8210aef1abf4
Clough, G.
9f19639e-a929-4976-ac35-259f9011c494
Calder, P.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Byrne, C.
1370b997-cead-4229-83a7-53301ed2a43c

Bhatia, L., Scorletti, E., Curzen, N., Clough, G., Calder, P. and Byrne, C. (2016) Improvement in non-alcoholic fatty liver disease severity is associated with a reduction in carotid intima-media thickness progression. Atherosclerosis, 246, 13-20. (doi:10.1016/j.atherosclerosis.2015.12.028). (PMID:26748347)

Record type: Article

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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More information

Accepted/In Press date: 21 December 2015
e-pub ahead of print date: 24 December 2015
Published date: March 2016
Keywords: carotid intima-media thickness, non-alcoholic fatty liver disease, fatty acids, omega-3, cardiovascular disease, atherosclerosis
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 385796
URI: https://eprints.soton.ac.uk/id/eprint/385796
ISSN: 0021-9150
PURE UUID: a6dd2eb2-6ebe-488f-a242-6d60d28c4261
ORCID for L. Bhatia: ORCID iD orcid.org/0000-0002-7379-0686
ORCID for G. Clough: ORCID iD orcid.org/0000-0002-6226-8964
ORCID for C. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 25 Jan 2016 09:00
Last modified: 06 Jun 2018 13:02

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