Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Sep 27, 2023; 15(9): 1043-1059
Published online Sep 27, 2023. doi: 10.4254/wjh.v15.i9.1043
Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet
Yun-Kai Dai, Hai-Na Fan, Kai Huang, Xin Sun, Zhi-Min Zhao, Cheng-Hai Liu
Yun-Kai Dai, Hai-Na Fan, Xin Sun, Zhi-Min Zhao, Cheng-Hai Liu, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, Shanghai 201203, China
Kai Huang, Xin Sun, Zhi-Min Zhao, Cheng-Hai Liu, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases, Shanghai 201203, China
Cheng-Hai Liu, Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shanghai 201203, China
Author contributions: Liu CH and Zhao ZM conceived and designed the study; Dai YK, Fan HN, Huang K and Sun X performed the experiment; Dai YK, Fan HN, Huang K and Sun X analyzed the data; Dai YK wrote the paper; Liu CH and Zhao ZM contributed to supervision; All authors approved the final manuscript as submitted.
Supported by National Science and Technology Major Project, No. 2014ZX10005001 and No. 2018ZX10302204; National Natural Science Foundation of China, No. 81730109 and No. 82274305; Shanghai Key Specialty of Traditional Chinese Clinical Medicine, No. shslczdzk01201; China Postdoctoral Science Foundation, No. 2022M722162; Siming Youth Fund of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. SGKJ-202104.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
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: Cheng-Hai Liu, MD, PhD, Director, Doctor, Professor, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, No. 528 Zhangheng Road, Pudong New Area, Shanghai 201203, China. chenghai.liu@shutcm.edu.cn
Received: June 8, 2023
Peer-review started: June 8, 2023
First decision: August 5, 2023
Revised: August 21, 2023
Accepted: September 14, 2023
Article in press: September 14, 2023
Published online: September 27, 2023
Processing time: 106 Days and 8.5 Hours
Abstract
BACKGROUND

After receiving entecavir or combined with FuzhengHuayu tablet (FZHY) treatment, some sufferers with hepatitis B virus (HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen. Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.

AIM

To explore baseline serum metabolites characteristics in responders.

METHODS

A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited. First, all subjects were divided into training set and validation set. Second, the included patients were subdivided into entecavir responders (E-R), entecavir no-responders (E-N), FZHY + entecavir responders (F-R), and FZHY + entecavir no-responders (F-N) following the pathological histological changes after 48 wk’ treatments. Then, Serum samples of all subjects before treatment were tested by high performance liquid chromatography-tandem mass spectrometry (LC-MS) high-performance LC-MS. Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis. Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.

RESULTS

As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N, results showed that 4 pathways including linoleic acid metabolism, aminoacyl-tRNA biosynthesis, cyanoamino acid metabolism, alanine, aspartate and glutamate metabolism were screened out. As for the differential metabolites, these 7 intersected metabolites including hydroxypropionic acid, tyrosine, citric acid, taurochenodeoxycholic acid, benzoic acid, 2-Furoic acid, and propionic acid were selected.

CONCLUSION

Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Keywords: Serum metabolomics; Differential metabolites; Therapeutic responders; Entecavir; FuzhengHuayu tablet; Hepatitis B virus-related liver fibrosis

Core Tip: This study will use high-performance liquid chromatography-tandem mass spectrometry and multivariate statistical modelings to predict serum metabolites of the treatment (entecavir or entecavir + FuzhengHuayu tablet) that effectively reversed hepatitis B virus-related liver fibrosis. It is of great theoretical and practical significance to prevent the transformation of liver fibrosis to cirrhosis or even hepatocellular carcinoma and reduce the social burden.