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.