Clinical Trials Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2017; 23(15): 2771-2784
Published online Apr 21, 2017. doi: 10.3748/wjg.v23.i15.2771
Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease
Shu Dong, Zong-Ying Zhan, Hong-Yan Cao, Chao Wu, Yan-Qin Bian, Jian-Yuan Li, Gen-Hong Cheng, Ping Liu, Ming-Yu Sun
Shu Dong, Zong-Ying Zhan, Hong-Yan Cao, Chao Wu, Yan-Qin Bian, Jian-Yuan Li, Ping Liu, Ming-Yu Sun, Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Shu Dong, Zong-Ying Zhan, Hong-Yan Cao, Chao Wu, Yan-Qin Bian, Jian-Yuan Li, Ping Liu, Ming-Yu Sun, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Gen-Hong Cheng, Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States
Author contributions: Dong S, Zhan ZY, Liu P and Sun MY conceived and designed the experiments; Dong S and Sun MY wrote the paper; Dong S, Zhan ZY, Cao HY, Wu C, Bian YQ and Li JY collected the samples; Sun MY and Cheng GH critically revised the paper for important intellectual content; Sun MY gave final approval for publication of the paper.
Supported by the Major Project of Shanghai Municipal S&T Commission, No. 15DZ1900104; and National Natural Science Foundation of China, No. 81273729.
Institutional review board statement: The study protocol was approved by the Ethics Review Committee of the Faculty of Medicine, Shuguang Hospital, China, and was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines.
Clinical trial registration statement: This study has been registered on ClinicalTrials.gov. Identifier No. NCT02077283.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest regarding the publication of this paper.
Data sharing statement: Readers can obtain the information of the study and the original data by contacting the author Shu Dong at lisadongshu@163.com.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Ming-Yu Sun, MD, PhD, Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai 201203, China. mysun248@hotmail.com
Telephone: +86-21-20256520
Received: December 5, 2016
Peer-review started: December 6, 2016
First decision: December 29, 2016
Revised: January 13, 2017
Accepted: February 17, 2017
Article in press: February 17, 2017
Published online: April 21, 2017
Processing time: 135 Days and 23.8 Hours
Abstract
AIM

To identify a panel of biomarkers that can distinguish between non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and explore molecular mechanism involved in the process of developing NASH from NAFLD.

METHODS

Biomarkers may differ during stages of NAFLD. Urine and blood were obtained from non-diabetic subjects with NAFLD and steatosis, with normal liver function (n = 33), from patients with NASH, with abnormal liver function (n = 45), and from healthy age and sex-matched controls (n = 30). Samples were subjected to metabolomic analysis to identify potential non-invasive biomarkers. Differences in urinary metabolic profiles were analyzed using liquid chromatography tandem mass spectrometry with principal component analysis and partial least squares-discriminate analysis.

RESULTS

Compared with NAFLD patients, patients with NASH had abnormal liver function and high serum lipid concentrations. Urinary metabonomics found differences in 31 metabolites between these two groups, including differences in nucleic acids and amino acids. Pathway analysis based on overlapping metabolites showed that pathways of energy and amino acid metabolism, as well as the pentose phosphate pathway, were closely associated with pathological processes in NAFLD and NASH.

CONCLUSION

These findings suggested that a panel of biomarkers could distinguish between NAFLD and NASH, and could help to determine the molecular mechanism involved in the process of developing NASH from NAFLD. Urinary biomarkers may be diagnostic in these patients and could be used to assess responses to therapeutic interventions.

Keywords: Urinary metabonomics; Nonalcoholic fatty liver disease; Steatohepatitis

Core tip: To identify biomarkers that can distinguish between nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), urine and blood were obtained from patients with NAFLD and NASH, and healthy controls. Urinary metabonomics found differences in 31 metabolites between NAFLD and NASH, including nucleic acids and amino acids. Pathway analysis showed that pathways of energy metabolism, amino acid metabolism, and the pentose phosphate pathway, were closely associated with the pathological processes in NAFLD and NASH. These biomarkers could distinguish between NAFLD and NASH, and could help to determine the mechanism involved in the development of NASH from NAFLD.