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Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease : A double-blind, randomized, placebo-controlled study

Oscarsson, Jan; Önnerhag, Kristina LU ; Risérus, Ulf; Sundén, Mattias; Johansson, Lars; Jansson, Per Anders; Moris, Linda; Nilsson, Peter M. LU ; Eriksson, Jan W. and Lind, Lars (2018) In Journal of Clinical Lipidology 12(6). p.4-1403
Abstract

Background: Treatment with omega-3 fatty acids and fenofibrates reduces serum triglyceride levels, but few studies have compared the effect of these agents on liver fat. Objective: The aim of the EFFECT I trial (NCT02354976) was to determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate on liver fat in overweight or obese individuals with non-alcoholic fatty liver disease and hypertriglyceridemia. Methods: Seventy-eight patients were randomized to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver proton density fat fraction (PDFF) and volume, pancreas volume, and adipose tissue volumes were assessed by magnetic... (More)

Background: Treatment with omega-3 fatty acids and fenofibrates reduces serum triglyceride levels, but few studies have compared the effect of these agents on liver fat. Objective: The aim of the EFFECT I trial (NCT02354976) was to determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate on liver fat in overweight or obese individuals with non-alcoholic fatty liver disease and hypertriglyceridemia. Methods: Seventy-eight patients were randomized to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver proton density fat fraction (PDFF) and volume, pancreas volume, and adipose tissue volumes were assessed by magnetic resonance imaging. Results: Changes in liver PDFF at 12 weeks were not significantly different across treatment groups (relative changes from baseline: placebo, +4%; OM-3CA, −2%; and fenofibrate, +17%). The common PNPLA3 genetic polymorphism (I148M) did not significantly influence the effects of OM-3CA or fenofibrate on liver PDFF. Fenofibrate treatment significantly increased liver and pancreas volumes vs placebo treatment, and the changes in liver and pancreas volumes were positively correlated (rho 0.45, P =.02). Total liver fat volume increased significantly in patients using fenofibrate vs OM-3CA (+23% vs −3%, P =.04). Compared with OM-3CA, fenofibrate increased total liver fat and liver volume. Serum triglycerides decreased with OM-3CA (−26%, P =.02) and fenofibrate (−38%, P <.001) vs placebo. In contrast to OM-3CA, fenofibrate reduced plasma docosahexaenoic acid levels and increased plasma acetylcarnitine and butyrylcarnitine levels, estimated delta-9 desaturase activity and the concentration of urine F2-isoprostanes. Conclusions: OM-3CA and fenofibrate reduced serum triglycerides but did not reduce liver fat. Fenofibrate increased total liver volume and total liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human hepatic lipid metabolism.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Cholesterol, Fatty liver disease, Lipoproteins, Liver, Non-alcoholic fatty liver disease, Omega-3 fatty acids, Pancreas, PPARs, Triglycerides
in
Journal of Clinical Lipidology
volume
12
issue
6
pages
4 - 1403
external identifiers
  • scopus:85052935672
ISSN
1933-2874
DOI
10.1016/j.jacl.2018.08.003
language
English
LU publication?
yes
id
9cfce8af-84be-43aa-b24b-c3a05913cec4
date added to LUP
2018-10-23 12:12:38
date last changed
2019-02-20 11:33:04
@article{9cfce8af-84be-43aa-b24b-c3a05913cec4,
  abstract     = {<p>Background: Treatment with omega-3 fatty acids and fenofibrates reduces serum triglyceride levels, but few studies have compared the effect of these agents on liver fat. Objective: The aim of the EFFECT I trial (NCT02354976) was to determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate on liver fat in overweight or obese individuals with non-alcoholic fatty liver disease and hypertriglyceridemia. Methods: Seventy-eight patients were randomized to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver proton density fat fraction (PDFF) and volume, pancreas volume, and adipose tissue volumes were assessed by magnetic resonance imaging. Results: Changes in liver PDFF at 12 weeks were not significantly different across treatment groups (relative changes from baseline: placebo, +4%; OM-3CA, −2%; and fenofibrate, +17%). The common PNPLA3 genetic polymorphism (I148M) did not significantly influence the effects of OM-3CA or fenofibrate on liver PDFF. Fenofibrate treatment significantly increased liver and pancreas volumes vs placebo treatment, and the changes in liver and pancreas volumes were positively correlated (rho 0.45, P =.02). Total liver fat volume increased significantly in patients using fenofibrate vs OM-3CA (+23% vs −3%, P =.04). Compared with OM-3CA, fenofibrate increased total liver fat and liver volume. Serum triglycerides decreased with OM-3CA (−26%, P =.02) and fenofibrate (−38%, P &lt;.001) vs placebo. In contrast to OM-3CA, fenofibrate reduced plasma docosahexaenoic acid levels and increased plasma acetylcarnitine and butyrylcarnitine levels, estimated delta-9 desaturase activity and the concentration of urine F2-isoprostanes. Conclusions: OM-3CA and fenofibrate reduced serum triglycerides but did not reduce liver fat. Fenofibrate increased total liver volume and total liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human hepatic lipid metabolism.</p>},
  author       = {Oscarsson, Jan and Önnerhag, Kristina and Risérus, Ulf and Sundén, Mattias and Johansson, Lars and Jansson, Per Anders and Moris, Linda and Nilsson, Peter M. and Eriksson, Jan W. and Lind, Lars},
  issn         = {1933-2874},
  keyword      = {Cholesterol,Fatty liver disease,Lipoproteins,Liver,Non-alcoholic fatty liver disease,Omega-3 fatty acids,Pancreas,PPARs,Triglycerides},
  language     = {eng},
  number       = {6},
  pages        = {4--1403},
  series       = {Journal of Clinical Lipidology},
  title        = {Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease : A double-blind, randomized, placebo-controlled study},
  url          = {http://dx.doi.org/10.1016/j.jacl.2018.08.003},
  volume       = {12},
  year         = {2018},
}