Observational Study
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World J Gastroenterol. Oct 21, 2022; 28(39): 5764-5783
Published online Oct 21, 2022. doi: 10.3748/wjg.v28.i39.5764
Serum metabolic profiling of targeted bile acids reveals potentially novel biomarkers for primary biliary cholangitis and autoimmune hepatitis
Zhen-Hua Ma, Xiao-Mei Wang, Rui-Hong Wu, Da-Lin Hao, Li-Chao Sun, Pan Li, Jun-Qi Niu
Zhen-Hua Ma, Da-Lin Hao, Li-Chao Sun, Department of Infection and Hepatology, The Affiliated Hospital of Beihua University, Jilin 132011, Jilin Province, China
Xiao-Mei Wang, Rui-Hong Wu, Jun-Qi Niu, Department of Hepatology, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
Pan Li, Department of Pathology, The Affiliated Hospital of Beihua University, Jilin 132011, Jilin Province, China
Author contributions: Niu JQ contributed to conception and design of the research, review and editing; Ma ZH, Sun LC, and Li P contributed to investigation and wrote the manuscript; Ma ZH, Wang XM, and Wu RH contributed to acquisition of data and statistical analysis; Hao DL contributed to funding acquisition; all authors have read and approve the final manuscript.
Supported by Health and Family Planning Commission Project of Jilin Province, No. 2016Q043; and Health and Hygiene Committee Project of Jilin Province, No. 2021LC082.
Institutional review board statement: The study protocol was carefully reviewed and approved by the Institutional Review Board (IRB) of the Affiliated Hospital of the Medical School of Jilin University, No. 2009-017.
Informed consent statement: All the eligible patients and HCs signed the written informed consent form prior to enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Jun-Qi Niu, MMed, Professor, Department of Hepatology, The First Hospital of Jilin University, No. 1 Xinmin Dajie, Chaoyang District, Changchun 130061, Jilin Province, China. junqiniu@jlu.edu.cn
Received: June 28, 2022
Peer-review started: June 28, 2022
First decision: August 19, 2022
Revised: September 7, 2022
Accepted: September 23, 2022
Article in press: September 23, 2022
Published online: October 21, 2022
Processing time: 112 Days and 2.7 Hours
Abstract
BACKGROUND

Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are two unexplained immune diseases. The golden standard for diagnosis of these diseases requires a liver biopsy. Liver biopsy is not widely accepted by patients because of its invasive nature, and atypical liver histology can confuse diagnosis. In view of the lack of effective diagnostic markers for PBC and AIH, combined with the increasingly mature metabolomics technologies, including full-contour metabolomics and target.

AIM

To determine non-invasive, reliable, and sensitive biochemical markers for the differential diagnosis of PBC and AIH.

METHODS

Serum samples from 54 patients with PBC, 26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry serum metabolomics. The metabolites and metabolic pathways were identified, and the metabolic changes, metabolic pathways and inter-group differences between PBC and AIH were analyzed. Fifteen kinds of target metabolites of bile acids (BAs) were quantitatively analyzed by SRM, and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis.

RESULTS

We found the changes in the levels of amino acids, BAs, organic acids, phospholipids, choline, sugar, and sugar alcohols in patients with PBC and AIH. Furthermore, the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid, lithocholic acid (LCA), taurolithocholic acid (TLCA), and LCA + TLCA in the PBC group compared with those in the AIH group. The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases. The levels of glycochenodeoxycholic acid, glycochenodeoxycholic sulfate, and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class, which was correlated with the severity of disease.

CONCLUSION

The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.

Keywords: Primary biliary cholangitis; Autoimmune hepatitis; Biomarkers; Serum metabolic profiling; Bile acids; Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry

Core Tip: Using full-contour metabolomics and SRM, to determine non-invasive, reliable, and sensitive biochemical markers for the differential diagnosis of primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). We revealed the increased levels of chenodeoxycholic acid, lithocholic acid (LCA), taurolithocholic acid (TLCA), and LCA + TLCA in the PBC group compared with those in the AIH group. The levels of glycochenodeoxycholic acid, glycochenodeoxycholic sulfate, and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class, which was correlated with the severity of disease. The levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.