Effects of purified eicosapentaenoic and docosahexaenoic... : Hepatology (original) (raw)

Steatohepatitis/Metabolic Liver Disease

**Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: Results from the WELCOME* study**

Scorletti, Eleonora1,2; Bhatia, Lokpal1,2; McCormick, Keith G.1; Clough, Geraldine F.1; Nash, Kathryn3; Hodson, Leanne4; Moyses, Helen E.2; Calder, Philip C.1,2; Byrne, Christopher D.1,2; Sheron, Nick M.D., FRCP, Head of Clinical Hepatology; Wright, Mark B.Sc. (Hons.), MBBS (Hons.), MRCP, Ph.D.; Curzen, Nick Professor B.M. (Hons.), Ph.D., FRCP, FESC; Rakhit, Dhrubo MBBS, B.Sc., MRCP, Ph.D.; Peebles, Charles MBBS, MRCP, FRCR; Darekar, Angela Ph.D.; Fletcher, Alison Ph.D.; Bateman, Adrian B.Sc., M.D., M.R.C.Path.; Williams, Elizabeth B.M., Ph.D., FRCP; Aspinall, Richard M.B.Ch.B., Ph.D., MRCP; Fowell, Andrew B.Sc., B.M., MRCP, Ph.D.; Richardson, Tristan B.Sc., MBBS, FRCP; Li Voon Chong, J. S.W. B.A., M.B. B.Ch., BAO, M.D., MRCPI, FRCP; Al-Mrayat, Maén MBBS, FRCP, Victor Lawrence, B.Sc., MBBS, MRCP, Ph.D. on behalf of the WELCOME Study Investigators

From the 1 Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; 2National Institute for Health Research Southampton Biomedical Research Center (in Nutrition) and Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK; 3Hepatology, University Hospital Southampton, NHS Foundation Trust, Southampton, UK; 4Oxford Center for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Oxford, UK.

Received 25 April 2014; revised 5 June 2014; accepted 22 June 2014

Published online 25 August 2014.

Address reprint requests to: Christopher D. Byrne, M.B., B.Ch., Ph.D., Nutrition and Metabolism Unit, Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, IDS Building, MP 887, Southampton General Hospital, Southampton SO16 6YD, United Kingdom. E-mail:[email protected]; fax: +44 (0)2380 79 4221.

Potential conflict of interest: Dr. Calder consults and is on the speakers' bureau for Vifor. He consults for Amarin and advises Pronova.

The WELCOME acronym is derived from: Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy.

This work was supported by the National Institute of Health Research (NIHR) through the NIHR Southampton NIHR Biomedical Research Unit in Nutrition (and Lifestyle), by Diabetes UK, and by the Parnell Diabetes Trust.

Abstract

There is no licensed treatment for nonalcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes, and cardiovascular disease. We tested whether 15–18 months of treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA; Omacor/Lovaza, 4 g/day) decreased liver fat and improved two histologically validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomized in a double-blind, placebo-controlled trial (DHA+EPA, n = 51; placebo, n = 52). We quantified liver fat percentage by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA; placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of (1) DHA+EPA treatment (intention-to-treat analyses) and (2) erythrocyte DHA and EPA enrichment (secondary analysis). Median (interquartile range) baseline and end-of-study liver fat percentage were 21.7 (19.3) and 19.7 (18.0) (placebo) and 23.0 (36.2) and 16.3 (22.0) (DHA+EPA). In the fully adjusted regression model, there was a trend toward improvement in liver fat percentage with DHA+EPA treatment (β = −3.64; 95% confidence interval [CI]: −8.0, 0.8; P = 0.1), but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat percentage (for each 1% enrichment: β = −1.70; 95% CI: −2.9, −0.5; P = 0.007). No improvement in fibrosis scores occurred. Conclusion: Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat percentage. Substantial decreases in liver fat percentage can be achieved with high-percentage erythrocyte DHA enrichment in NAFLD. (Hepatology 2014;60:1211–1221)