Editor's Note: As of 2022, there are 257.5 million people worldwide who are HBsAg positive. Decompensated cirrhosis and hepatocellular carcinoma (HCC) are the leading causes of death among chronic HBV patients. Liver biopsy is the "gold standard" for diagnosing fibrosis stages, but its invasive nature makes many patients reluctant to undergo the procedure. Recently, a study published in Hepatology International explored the value of serum N-glycan markers in diagnosing liver fibrosis.Background
Accurately assessing fibrosis staging is crucial for the diagnosis and monitoring of chronic hepatitis B (CHB). Methods to evaluate fibrosis include liver biopsy and non-invasive methods. While liver biopsy is the “gold standard,” it has complications such as pain (30%-50%), severe bleeding (0.6%), injury to other organs (0.08%), and in rare cases, death (up to 0.1%). Because of these risks, many patients and doctors are hesitant to perform liver biopsies. Non-invasive methods, such as liver stiffness measurement and serum biomarkers, are used to assess fibrosis severity.
Glycosylation is one of the main forms of post-translational modification of proteins. It is estimated that about 50% of proteins in the human body are glycoproteins, most of which contain N-glycan structures. Serum N-glycans are valuable in evaluating liver diseases. Previous research involving 450 CHB patients indicated that branched α(1,3)-fucosylated triantennary glycan was more abundant in HCC patients compared to cirrhosis patients [median 3.7 (95% CI: 3.5-3.9) vs. 2.3 (95% CI: 2.0-2.6)]; N-glycan markers also outperformed AFP in diagnosing HCC (AUROC 0.81 vs. 0.78). Additionally, previous studies found that N-glycan markers using machine learning effectively diagnosed fibrosis and cirrhosis in CHB patients with normal ALT levels. This study aimed to explore the value of serum N-glycan markers in evaluating liver fibrosis.
Methods
This multicenter study (33 hospitals) included 760 treatment-naive CHB subjects who underwent liver biopsy. Serum N-glycan markers were analyzed using fluorescent capillary electrophoresis on a DNA sequencer (DSA-FACE). Researchers first examined the relationship between 12 serum N-glycan markers and fibrosis staging. They then developed a Px score using LASSO regression to diagnose significant fibrosis. The diagnostic performance of Px was compared with liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis-4 index (FIB-4). Finally, RNA transcriptome sequencing was used to explore the relationship between glycosyltransferase genes and liver fibrosis.
Results
The study included 622 CHB subjects: predominantly male (69.6%), with a median age of 42.0 years (IQR 34.0-50.0); 287 subjects had normal ALT levels; 73.0% had significant fibrosis. P5 (NA2), P8 (NA3), and P10 (NA4) were inversely related to fibrosis severity, while other features [except P0 (NGA2)] increased with fibrosis severity.
Seven profiles were selected for the Px score [P1 (NGA2F), P2 (NGA2FB), P3 (NG1A2F), P4 (NG1A2F), P7 (NA2FB), P8 (NA3), and P9 (NA3Fb)]. In a fully adjusted generalized linear model, an increase in the Px score was associated with a 3.54-fold increased risk of significant fibrosis [OR=4.54 (2.63-7.82), P<0.001]. The diagnostic performance of the Px score outperformed other scores. Glycosyltransferase genes were overexpressed in liver fibrosis, with significant enrichment in glycosylation and glycosyltransferase-related pathways.
Conclusion
Serum N-glycan markers are positively correlated with liver fibrosis. The Px score shows good performance in distinguishing significant fibrosis.
