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Licensed Unlicensed Requires Authentication Published by De Gruyter January 8, 2021

Serum N-glycan fingerprint nomogram predicts liver fibrosis: a multicenter study

  • Chenjun Huang ORCID logo , Lijuan Liu , Hao Wang , Meng Fang , Huijuan Feng , Ya Li , Mengmeng Wang , Lin Tong , Xiao Xiao , Ziyi Wang , Xuewen Xu , Yutong He and Chunfang Gao EMAIL logo

Abstract

Objectives

Liver cirrhosis (LC) is the end-stage of fibrosis in chronic liver diseases, non-invasive early detection of liver fibrosis (LF) is particularly essential for therapeutic decision. Aberrant glycosylation of glycoproteins has been demonstrated to be closely related to liver abnormalities.

Methods

This study was designed to enroll a total of 1,565 participants with LC/LF, chronic hepatitis virus (CHB) and healthy controls. Fibrosis was confirmed by liver biopsy. Using capillary electrophoresis N-glycan fingerprint (NGFP) analysis, we developed a nomogram algorithm (FIB-G) to discriminate LC from non-cirrhotic subjects.

Results

The FIB-G demonstrated good diagnostic performances in identifying LC with the area under the curve (AUC) 0.895 (95%CI: 0.857–0.915). Furthermore, the diagnostic efficiencies of FIB-G were superior to that of log (P2/P8), procollagen III N-terminal (PIIINP), type IV collage (IV-C), laminin (LN), hyaluronic acid (HA), aspartate transaminase to platelets ratio index (APRI), and FIB-4 when detecting significant fibrosis (S0–1 vs. S2–4, AUC: 0.787, 95%CI: 0.701–0.873), severe fibrosis (S0–2 vs. S3–4, AUC: 0.844, 95%CI: 0.763–0.924), and LC (S0–3 vs. S4, AUC: 0.773, 95%CI: 0.667–0.880). Besides, changes of FIB-G were associated well with the regression of fibrosis and liver function Child–Pugh classification.

Conclusions

FIB-G is an accurate multivariant N-glycomic algorithm for LC prediction and fibrosis progression/regression monitoring. The high throughput feasible NGFP using only 2 μL of serum could help physicians make the more precise non-invasive staging of LF or cirrhosis and reduce the need for invasive liver biopsy.


Corresponding author: Chunfang Gao, MD, PhD, Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, 225 Changhai Road, Shanghai, 200438, P.R. China, Phone: +86 21 81875130, Fax: +86 21 65562400, E-mail:
Chenjun Huang, Lijuan Liu and Hao Wang contributed equally to this work.

Funding source: China National Key Projects for Infectious Disease

Award Identifier / Grant number: 2018ZX10302205-003

Funding source: Shanghai Science and Technology Commission

Award Identifier / Grant number: 17411960500

Award Identifier / Grant number: 17JC1404500

Acknowledgments

We are very grateful to Shanghai Jing’an District Central Hospital for providing liver fibrosis samples. We are grateful for Ms. Minfan Xu and Ms. Song Hong for the help of sample collection.

  1. Research funding: This work was supported by the China National Key Projects for Infectious Disease (2018ZX10302205-003), the Shanghai Science and Technology Commission (17411960500; 17JC1404500).

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: All authors claim that there is no conflict of interest including a desire for financial gain, prominence, professional advancement or a successful outcome.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study was approved by the Institutional Review Boards at the leading study center. Informed consent was obtained from each participant.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-1588).


Received: 2020-10-20
Accepted: 2020-12-11
Published Online: 2021-01-08
Published in Print: 2021-05-26

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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