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

Abstract

on behalf of the WELCOME Study InvestigatorsThere 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 (DHA1EPA, n 5 51; placebo, n 5 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) DHA1EPA 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) (DHA1EPA). In the fully adjusted regression model, there was a trend toward improvement in liver fat percentage with DHA1EPA treatment (b 5 23.64; 95% confidence interval [CI]: 28.0, 0.8; P 5 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: b 5 21.70; 95% CI: 22.9, 20.5; P 5 0.007). No improvement in fibrosis scores occurred. Conclusion: Erythrocyte DHA enrichment with DHA1EPA 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

Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial

“…Consort diagram and the baseline characteristics of both placebo and active groups have been reported previously (5). All participants had NAFLD and features of metabolic syndrome.…”

“…Omega-3 polyunsaturated fatty acid (PUFA) treatment (3) and weight loss (4) can be effective in decreasing liver fat and also triglyceride concentrations. Recently in patients with NAFLD we have suggested that the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3) may be more effective that the omega-3 fatty acid eicosapentanoic acid (EPA; 20:5n-3) in decreasing liver fat (5). In this randomised placebo-controlled trial that tested the effects of high dose purified omega-3 fatty acids, we showed an association between high levels of erythrocyte DHA, but not EPA, enrichment and decreased liver fat.…”

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease

“…In a phase 2 double-blind, randomized, placebo-controlled trial, treatment with low-dosage (1800 mg/day) or high-dosage (2700 mg/day) ethyl-eicosapentanoic acid for 12 months had no significant effects on the histologic features of NASH 137 . In contrast, others have shown a benefit of n-3 PUFA treatment on liver fat assessed by magnetic resonance imaging (and have suggested that a greater benefit in NAFLD was associated with docosahexanoic acid treatment) [138][139][140] . Additionally, it has been suggested that the PNPLA3 148MM may attenuate any beneficial effect conferred by n-3 PUFA treatment in NAFLD 141 , emphasizing that future clinical trials testing new potential treatments for NAFLD should also perhaps consider the influence of different genotypes to modify any treatment effect.…”

NAFLD therapy and monitoring disease progression

“…94,95 Role of lipid-lowering drugs in NAFLD is inconclusive. While there is some data suggesting improvement in NASH with statins, 96 99 While there are few available treatment options of proven efficacy in NAFLD, promising drugs are under development and under evaluation for regulatory approval.…”