Mac‐2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection

Mac‐2 binding protein glycosylation isomer (M2BPGi) is a novel glycoprotein biomarker that correlates with liver fibrosis. It has been investigated in East Asian populations as a hepatocellular carcinoma (HCC) biomarker. We assessed M2BPGi as an HCC biomarker in an ethnically diverse cohort of patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We enrolled 947 treatment‐naive patients mono‐infected with HBV or HCV without HCC at baseline. Biomarker levels were measured from baseline sera and correlated with longitudinal clinical data. The primary outcome was HCC occurrence during long‐term follow‐up. Median M2BPGi was significantly higher among patients with cirrhosis (2.67 versus 0.80; P < 0.001) and patients who developed HCC (3.22 versus 1.16; P < 0.001). The area under the receiver operating characteristic (AUROC) for M2BPGi and alpha‐fetoprotein (AFP) was similar overall (0.77 versus 0.72; P = 0.15), but M2BPGi outperformed AFP among patients with HBV (0.84 versus 0.75; P = 0.02). M2BPGi performed poorly among patients with HCV (AUROC, 0.51). M2BPGi was an independent predictor of HCC among patients with HBV but not among patients with HCV. M2BPGi performed better in patient subgroups with a lower prevalence of cirrhosis. Conclusion: In our HBV cohort, M2BPGi was more effective than AFP in predicting HCC and was an independent predictor of HCC. However, M2BPGi had limited predictive value in our HCV cohort, likely due to a high cirrhosis burden in this cohort. Further studies are needed to evaluate M2BPGi as an HCC biomarker in broader patient populations with more diverse disease etiology, non‐Asian ethnicity, and more advanced fibrosis.