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

Clin Chem Lab Med. 2021 Jan 8;59(6):1087-1097. doi: 10.1515/cclm-2020-1588. Print 2021 May 26.

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.

Keywords: N-glycan; liver cirrhosis; liver fibrosis; nomogram; prediction.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartate Aminotransferases
  • Biomarkers
  • Biopsy
  • Humans
  • Liver / pathology
  • Liver Cirrhosis* / diagnosis
  • Nomograms*
  • Polysaccharides
  • ROC Curve
  • Retrospective Studies

Substances

  • Biomarkers
  • Polysaccharides
  • Aspartate Aminotransferases