Serum Mac-2-binding protein glycosylation isomer in assessing liver fibrosis in chronic hepatitis B infection

Abstract

Background and Aims: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum marker for diagnosis of liver fibrosis in various liver diseases, while data in chronic hepatitis B (CHB), especially longitudinal data, is limited.We aimed to evaluate the role of M2BPGi in diagnosing advanced fibrosis (F3) and cirrhosis (F4) in HBeAg-ve CHB using liver stiffness measurement (LSM) as the reference. Method: We performed transient elastography for HBeAg-ve CHB patients who were managed in Queen Mary Hospital, Hong Kong. LSM was performed by Fibroscan® (Echosens, Paris, France) and presence of no/minimal fibrosis (F0/F1), grey area and F3/F4 was defined using the alanine-aminotransferase-based EASL-ALEH criteria. Serum M2BPGi were measured using the HISCL-800 immunoanalyzer (Sysmex Corporation, Hyogo, Japan). Results: 240 HBeAg-ve CHB patients (M:F = 116:124) of median age 47.5 years were recruited. The majority were treatment-experienced (85.8%). The median ALT was 26 U/l (range: 10–180 U/l). The median liver stiffness was 6.9 kPa (IQR 4.9–11.7 kPa) and 78 of them (32.5%) had F3/F4 by transient elastography at baseline. The corresponding median M2BPGi values for F0/1/2, F3 and F4 progressively increased in parallel with more advanced stages of liver fibrosis: 0.39, 0.46 and 0.82 COI, respectively (p < 0.01) (Figure 1A). The AUROC for diagnosing ≥ F3 by serum M2BPGi was 0.754. Using a cut-off value of 0.605, the sensitivity, specificity, PPV and NPV for ≥ F3 was 62.5%, 79.4%, 60.3% and 80.9%, respectively. In a subgroup of 86 patients who had repeated LSM 10 years after the initial LSM, the proportion of patients with F3/4 was reduced from 36.7% to 16.3% (p < 0.001). The median serum M2BPGi levels were significantly different between patients with F3/4 compared to those with F0/1/2 at baseline (0.67 COI vs. 0.41 COI, p < 0.05) and also at 10-year (0.62 COI vs. 0.48 COI, p = 0.039). 21 (24.4%) showed significant fibrosis regression (i.e. F3 or F4 → F0 or F1). The median change in serum M2BPGi level was -0.11 compared to + 0.03 COI in the other patients who did not showed significant fibrosis regression (p = 0.011). (Figures 1C-1D) Conclusion: Serum M2BPGi was an accurate serum marker for liver fibrosis in HBeAg-ve CHB patients. Using a cut-off level of 0.605 COI, 80.9% patients without ≥ F3 can be excluded. Serum M2BPGi levels remained significantly higher for patients with ≥ F3 compared to those with F0/1/2 even after 10 years. Serum M2BPGi levels also decreased significantly in patients who had fibrosis regression after 10 years.