Role of serum M2BPGi levels on diagnosing significant liver fibrosis and cirrhosis in treated patients with chronic hepatitis B virus infection

Background: Mac-2-binding protein glycosylation isomer (M2BPGi), a novel serum marker for liver fibrosis, was seldom studied in chronic hepatitis B (CHB). We aimed to evaluate its role on diagnosing significant fibrosis and cirrhosis in treated CHB patients. Methods: CHB patients treated with nucleos(t) ide analogues (NAs) with baseline liver biopsies and retrievable serum samples were recruited. Paired liver biopsies were performed in patient subgroups at 1 and 3 years. Results: In total, 327 NA-treated CHB patients (M: F = 229: 98; median age 38.1 years) were recruited. The median M2BPGi values were 0.26, 0.34, 0.57 and 1.21 cutoff index (COI), in liver histology with Ishak F0-1, F2, F3 and F4, respectively (p < 0.01). M2BPGi levels correlated with the Ishak scores (rho = 0.312, p < 0.001). Using the cutoff values of 0.25, 0.45 and 0.96 COI for >= F2, >= F3 and F4, the AUROCs were 0.653, 0.795 and 0.914, respectively. Multivariate analysis with several other serum indices showed that M2BPGi was the most significant independent factor for >= F3 (OR: 8.197, 95% CI: 2.699-24.897, p < 0.001). In patient subgroups with serial liver biopsies, both the proportion of F3/F4 and M2BPGi decreased at 1 year (8.3% vs. 2.8% and 0.32 vs. 0.21 COI, respectively; both p < 0.001). Histological fibrosis progression after = 3 years of NA therapy accompanied with an increase in M2BPGi level, compared to patients without progression (+ 0.14 vs -0.03 COI, p = 0.045). Conclusion: Serum M2BPGi is a reliable non-invasive marker for diagnosing >= F2, >= F3 and F4. It is the only significant marker for >= F3 among several other indices. NA produced concordant dynamic changes in M2BPGi levels and histological fibrosis.