Role of serum M2BPGi levels in predicting persistence of advanced fibrosis in chronic hepatitis B virus infection

Abstract

Background: Mac-2-binding protein glycosylation isomer (M2BPGi) is a serum marker for liver fibrosis for various liver diseases including chronic hepatitis B (CHB). We aimed to evaluate its role in predicting persistence of advanced fibrosis (F3/F4) in CHB patients. Method: CHB patients with F3/F4 who were treated with nucleos(t)ide analogues (NAs) for ≥3 years with normal alanine aminotransferase and undetectable serum HBV DNA were prospectively recruited. Paired assessment with transient elastography (TE) and M2BPGi measurements were performed at baseline and 3 years. F3/F4 was defined by liver stiffness (LS) ≥9 kPa. Results: A total of 143 patients (M:F= 101:42; median age 58.7 years) were recruited and completed paired assessment. The baseline median LS and M2BPGi values were 12 (IQR: 10.5-18.2) kPa and 0.99 cut-off-index (IQR: 0.75-1.74) (COI), respectively, with 96% concordance for diagnosing F3/F4. Multivariate analysis showed that baseline M2BPGi (OR 2.128, 95% CI 1.037-4.366) and presence of central obesity (OR 4.648, 95% CI 1.742-12.402) were significantly associated with persistent F3/F4 at 3 years. Baseline M2BPGi ≥1.265 COI has 50.6% sensitivity and 79.4% specificity for predicting persistent F3/F4 at 3 years (AUROC: 0.695). Combining both the presence of central obesity and baseline M2BPGi ≥1.265 COI, 95.7% patients had persistent F3/F4. Five patients developed HCC during follow-up and were associated with bigger median relative percentage increment of serum M2BPGi compared to patients without HCC (46% vs 6.2%, P=0.038). Conclusion: Among CHB patients with F3/F4 diagnosed by TE, high serum M2BPGi was associated with persistent F3/F4 after 3 years of ongoing antiviral therapy.