Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2020; 8(21): 5235-5249
Published online Nov 6, 2020. doi: 10.12998/wjcc.v8.i21.5235
Essential phospholipids for nonalcoholic fatty liver disease associated with metabolic syndrome: A systematic review and network meta-analysis
Asad Izziddin Dajani, Branko Popovic
Asad Izziddin Dajani, ADSC, Medcare Hospital and Saudi German Hospital, Sharjah, Al Khan, PO Box 6328, United Arab Emirates
Branko Popovic, Sanofi-Aventis Deutschland GmbH, CHC Global Medical Affairs, Frankfurt am Main 65926, Germany
Author contributions: Popovic B contributed to the study design, and review and approval of the manuscript drafts; Dajani AI contributed to the study by reviewing the literature, analyzing the data, setting the conclusive remarks, and review and approval of the manuscript drafts; all authors revised all drafts for important intellectual content and approved the final version and its submission to The World Journal of Clinical Cases; all authors are accountable for the accuracy and integrity of the publication.
Conflict-of-interest statement: Branko Popovic is an employee of Sanofi. Dr. Dajani has no conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Branko Popovic, MD, Sanofi-Aventis Deutschland GmbH, CHC Global Medical Affairs, Industriepark Höchst, Frankfurt am Main 65926, Germany. branko.popovic@sanofi.com
Received: May 28, 2020
Peer-review started: May 28, 2020
First decision: July 29, 2020
Revised: September 11, 2020
Accepted: September 23, 2020
Article in press: September 23, 2020
Published online: November 6, 2020
Processing time: 162 Days and 1.4 Hours
ARTICLE HIGHLIGHTS
Research background

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent, particularly in patients with metabolic syndrome, but there are limited treatment options other than lifestyle changes. Preclinical data suggest that essential phospholipids (EPL) may inhibit the pathogenic processes that cause NAFLD. Therefore, EPL may be useful adjunctive therapy for patients with NAFLD in association with diabetes and/or obesity, but currently available data are limited.

Research motivation

Most of the data on the use of EPL in patients with NAFLD and diabetes and/or obesity are from small-scale studies, but we hypothesized that systematic evaluation and meta-analysis of these data may provide enough statistical power to assess the clinical effects of EPL in this population.

Research objectives

The aim of the current analysis was to apply meta-analytic techniques to data from clinical trials of EPL in high-risk NAFLD patients, specifically those with features of metabolic syndrome, to assess the effects of EPL, as monotherapy or as add-on therapy to existing treatment, on hepatic enzymes, lipid levels, and NAFLD severity.

Research methods

We searched MEDLINE, PubMed, Embase, and Cochrane databases up to March 2019 for clinical trials and comparative observational studies published in English or Chinese that enrolled adult patients (≥ 18 years) with NAFLD and type 2 diabetes mellitus and/or obesity receiving EPL as monotherapy or as add-on therapy to existing therapy, and that included at least one of the efficacy outcomes of interest. Because a variety of studies were identified, we performed a range of analysis, i.e. direct, indirect and cohort meta-analyses. A random-effects model was used to address between-study heterogeneity.

Research results

Ten studies met the inclusion criteria (n = 22-324). EPL treatment duration ranged from 4 to 72 wk. In the direct meta-analysis (four randomized controlled trials), compared with antidiabetic therapy alone, EPL plus antidiabetic therapy was associated with a significantly greater reduction in alanine aminotransferase (ALT), triglyceride, and total cholesterol levels, and a significant increase in the rate of overall improvement. There was a significant increase in the risk of no disease (P = 0.0091), and a reduction in moderate disease (P = 0.0187), but no significant differences in severe disease, mild disease, or significant improvement. In the cohort meta-analysis of three non-randomized clinical trials, the mean difference in ALT levels was -16.71 U/L and 23% of patients had improved disease. In the cohort meta-analysis of five randomized trials, the mean difference in ALT levels was -28.53 U/L, and 87% of patients showed clinical improvement and 58% showed significant clinical improvement.

Research conclusions

Although the data to date are limited and heterogeneous, the results of the current analyses provide evidence for a benefit of EPL in the high-risk groups of NAFLD patients with features of metabolic syndrome including type 2 diabetes and obesity.

Research perspectives

EPL warrant further investigation as a treatment for NAFLD patients, in large-scale studies with a long duration of follow-up.