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
Abstract
BACKGROUND

Essential phospholipids (EPL) are used for the supportive treatment of non-alcoholic fatty liver disease (NAFLD), but data are mostly from small-scale studies.

AIM

To evaluate the efficacy of EPL treatment in adult patients with NAFLD and type 2 diabetes and/or obesity.

METHODS

The MEDLINE, PubMed, Embase, and Cochrane databases were searched up to March 2019 for clinical trials and comparative observational studies. Eligible studies were those 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. A variety of studies were identified; thus, direct, indirect and cohort meta-analyses were performed. Mean difference (MD) and 95% confidence interval (CI) were calculated for continuous variables, and relative risk with 95%CI for disease response and recovery. A random-effects model was used to address between-study heterogeneity.

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); MD: 11.28 U/L (95%CI: -17.33, -5.23), P = 0.0003], triglyceride [MD: -49.33 mg/dL (95%CI: -66.43, -32.23), P < 0.0001] and total cholesterol levels [MD: -29.74 mg/dL (95%CI: -38.02, -21.45), P < 0.0001]. There was also a significant increase in the rate of overall improvement [relative risk 1.50 (95%CI: 1.26-1.79), P < 0.0001], and risk of no disease (P = 0.0091), and a reduction in moderate disease (P = 0.0187); there were no significant differences in severe disease, mild disease, or significant improvement. In the cohort meta-analysis of three non-randomized clinical trials, the MD in ALT levels was -16.71 U/L (95%CI: -24.94, -8.49) and 23% of patients had improved disease. In the cohort meta-analysis of five randomized trials, MD in ALT levels was –28.53 U/L (95%CI: -35.42, -21.65), and 87% (95%CI: 81%, 93%) and 58% (95%CI: 46%, 70%) of patients showed clinical improvement and significant clinical improvement.

CONCLUSION

This analysis provides evidence for a benefit of EPL in patients with NAFLD and diabetes and/or obesity. Further large-scale trials are warranted.

Keywords: Non-alcoholic fatty liver disease; Diabetes; Obesity; Metabolic syndrome; Essential phospholipids; Systematic review; Meta-analysis

Core Tip: Essential phospholipids (EPL) are used for the supportive treatment of non-alcoholic fatty liver disease, but the data are mostly from small-scale studies. Thus, we used meta-analytical techniques to assess the efficacy of EPL in patients with non-alcoholic fatty liver disease and type 2 diabetes and/or obesity. Our results indicate EPL provides benefit in this patient population, reducing alanine aminotransferase, triglyceride and cholesterol levels, and improving disease severity (as measured by ultrasonography). Larger-scale trials are warranted to confirm these findings.