Serum Mac-2-binding protein glycosylation isomer and risk of hepatocellular carcinoma in entecavir-treated chronic hepatitis B patients

Abstract

Background and Aim: Hepatocellular carcinoma (HCC) can still develop in chronic hepatitis B (CHB) patients receiving antiviral treatment. Serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis. We investigated its role on incidence of HCC in entecavir (ETV)‐treated CHB patients.

Methods: We identified HCC cases diagnosed at ≥ 1 year of ETV treatment. CHB patients without HCC (matched for age, gender, baseline hepatitis B virus‐DNA, and duration of ETV treatment) were identified in approximately 1:2 ratio (HCC: non‐HCC) for comparison. Serum samples were retrieved at baseline (initiation of ETV), 3, and 5 years of ETV for serum M2BPGi measurement (expressed in cut‐off index [COI]).

Results: One hundred HCC cases were matched with 185 CHB patients without HCC (median age 56.7 years, 78.9% male, baseline hepatitis B virus‐DNA 5.6 logIU/mL, and median follow‐up 7.1 years). Median time from ETV initiation to incident HCC was 3.9 years. Serum M2BPGi levels were significantly higher in HCC cases compared with controls at baseline and year 3 (1.25 vs 0.98 [P = 0.004], 0.89 vs 0.74 [P = 0.018] COI, respectively). Multivariate analysis showed that baseline M2BPGi was the only independent factor associated with incident HCC (odds ratio 1.241, 95% confidence interval 1.039–1.482, P = 0.017). Using a cut‐off value of 1.15 COI, the sensitivity, specificity, positive predictive value, and negative predictive value of baseline serum M2BPGi in cirrhotic patients to predict incident HCC were 90%, 53.8%, 69.6%, and 82.1%, respectively.

Conclusions: Baseline and 3‐year serum M2BPGi may be useful to identify high risk patients on antiviral treatment for subsequent HCC development.