Biomarker Applications in Liver Fibrosis Evaluation

Liver fibrosis is a dynamic process characterised by excessive deposition of extracellular matrix proteins following chronic hepatic injury. Accurate staging of fibrosis informs prognosis, guides therapeutic decisions and enables monitoring of disease progression or regression. Traditionally, liver biopsy has remained the gold standard but is limited by invasiveness, sampling variability and risk of complications. Over the past two decades, considerable effort has focused on the development and validation of non-invasive biomarkers spanning serum proteins, glycoprotein isomers, glycan signatures and imaging-derived indices. Serological tests such as the fibrosis-4 (FIB-4) index and aspartate transaminase to platelet ratio index (APRI) combine routine laboratory parameters to produce composite fibrosis scores, while novel glycotest markers—most notably Mac-2-binding protein glycosylation isomer (M2BPGi) and Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP)—leverage aberrant glycosylation patterns that correlate closely with fibrotic stage. In parallel, imaging modalities such as vibration-controlled transient elastography and magnetic resonance elastography have provided real-time, quantitative assessments of liver stiffness. Collectively, these approaches have revolutionised clinical pathways by enabling widespread screening, longitudinal monitoring and stratification of patients for emerging antifibrotic therapies.

Research from Nature Portfolio

Investigations have established WFA+-M2BP as an age-independent serum marker for advanced fibrosis in non-alcoholic fatty liver disease. In a cohort combining histological and elastographic assessments, this lectin-based assay achieved near-optimal discrimination of severe fibrosis with a single cutoff regardless of patient age, outperforming traditional indices that require age-adjusted thresholds. The consistency of WFA+-M2BP across demographic subgroups underscores its potential for large-scale screening and risk stratification in metabolic liver disease.

Biomarker Applications in Liver Fibrosis Evaluation publication trend

The graph below shows the total number of articles in biomarker applications in liver fibrosis evaluation across all publications each year (not limited to Nature Index journals).

Technical terms

M2BPGi: Mac-2-binding protein glycosylation isomer, a glycoprotein-based serological marker for staging liver fibrosis.

WFA+-M2BP: Wisteria floribunda agglutinin-positive Mac-2-binding protein, a lectin-based assay detecting specific glycosylation on M2BP related to fibrosis severity.

NAFLD: Non-alcoholic fatty liver disease, a spectrum of liver conditions characterised by fat accumulation unrelated to alcohol.

VCTE: Vibration-controlled transient elastography, an ultrasound-based method evaluating liver stiffness through shear wave velocity.

MRE: Magnetic resonance elastography, a non-invasive imaging technique measuring liver stiffness to assess fibrosis.

Fibrosis indices (e.g. FIB-4, APRI, NFS): Composite scores derived from routine laboratory tests to estimate fibrosis stage non-invasively.

References

1. M2BPgs-HCC: An Automated Multilectin Bead Array Indicating Aberrant Glycosylation Signatures Toward Hepatitis C Virus-Associated Hepatocellular Carcinoma Prognosis. Molecules (2024).
2. Diagnostic Performance of Serum Mac-2-Binding Protein Glycosylation Isomer as a Fibrosis Biomarker in Non-Obese and Obese Patients with MASLD. Biomedicines (2025).
3. Wisteria floribunda agglutinin-positive mac-2 binding protein as an age-independent fibrosis marker in nonalcoholic fatty liver disease. Scientific Reports (2019).