Systematic Reviews
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2023; 15(8): 1001-1012
Published online Aug 27, 2023. doi: 10.4254/wjh.v15.i8.1001
Emerging therapeutic options for non-alcoholic fatty liver disease: A systematic review
Jasmine Tidwell, Natalie Balassiano, Anjiya Shaikh, Mahmoud Nassar
Jasmine Tidwell, Anjiya Shaikh, Department of Internal Medicine, University of Connecticut, Farmington, CT 06032, United States
Natalie Balassiano, Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York, NY 11432, United States
Mahmoud Nassar, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY 14221, United States
Author contributions: Tidwell J and Balassiano N performed the screening of articles, extraction of data and wrote the manuscript; Tidwell J and Shaikh A contributed to the results and discussion section; Nassar M contributed to editing, formatting and reviewing; All authors have read and approve the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mahmoud Nassar, MD, MSc, PhD, Doctor, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, WNY 705 Maple Road, Williamsville, Buffalo, NY 14221, United States. dr.nassar@aucegypt.edu
Received: April 30, 2023
Peer-review started: April 30, 2023
First decision: June 7, 2023
Revised: June 18, 2023
Accepted: August 7, 2023
Article in press: August 7, 2023
Published online: August 27, 2023
ARTICLE HIGHLIGHTS
Research background

Non-alcoholic fatty liver disease (NAFLD) has become a global health issue with significant medical costs. The lack of a Federal Drug Administration (FDA)-approved medication for the treatment of NAFLD has prompted the investigation of several potential therapeutic classes. It is valuable to have a compilation of the data available on their efficacy.

Research motivation

Due to the absence of an approved medication by the FDA for the treatment of NAFLD, several therapeutic classes have been investigated in clinical trials. It is important to understand the mechanisms and statistical significance of the agents being investigated, as NAFLD is extremely prevalent.

Research objectives

To assess the efficacy of cyclophilin inhibitors, fibroblast growth factor 21 analogs (FGF21), and dual and pan peroxisome proliferator-activated receptor (PPAR) agonists as possible therapeutic classes for treating NAFLD.

Research methods

We searched PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science using keywords including cyclophilin inhibitor, FGF agonist, pan-PPAR agonists, dual-PPAR agonist, NAFLD, non-alcoholic steatohepatitis, and fatty liver. Articles with a National Institutes of Health Quality Assessment score of five or higher were included. Each article was screened by two independent researchers evaluating relevance and quality. Pertinent data were extracted in a spreadsheet and descriptively analyzed.

Research results

We identified 29 studies that met the necessary criteria and were included in this review. These records included 12 human studies and 17 animal studies. Specifically, there were four studies on cyclophilin inhibitors, four on FGF analogs, 11 on pan-PPAR agonists, and ten on dual-PPAR agonists. All classes were found to be efficacious for the treatment of NAFLD with statistical significance (P < 0.05).

Research conclusions

We found that cyclophilin inhibitors, fibroblast growth factor 21 analogs, and dual and pan PPAR agonists are not only statistically efficacious for the treatment of NAFLD but also generally well tolerated. We recommend more extensive human clinical research to further delineate therapy's efficacy, dosage, and duration.

Research perspectives

It is to be expected that additional human clinical trials of the therapeutic classes assessed in this review, as well as additional novel agents, will be conducted in the near future. An FDA-approved agent for the treatment of NAFLD is of utmost importance.