Serum Mac-2 Binding Protein Glycosylation Isomer in Predicting Hepatocellular Carcinoma Occurrence among Patients with Direct-Acting Antiviral-induced HCV Cure

Mac-2-binding protein glycosylation isomer (M2BPGi), a promising biomarker for predicting hepatocellular carcinoma (HCC), was evaluated in predicting HCC occurrence after hepatitis C virus (HCV) cure with direct-acting antivirals (DAAs). 704 eligible patients underwent biannual surveillance, including alpha-fetoprotein (AFP) and liver imaging studies, to detect HCC occurrence. Serum M2BPGi levels were measured at both pretreatment and sustained virologic response (SVR ₁₂ ). The cumulative HCC incidence was estimated by Kaplan-Meier analysis, and risk factors by Cox proportional hazards models. During a median follow-up of 4.5 years, 50 patients (7.1%) developed HCC, with cumulative incidence rates of 7.8% and 12.8% at 5 and 10 years. HCC incidence was higher in patients with pretreatment M2BPGi ≥ 4.0 and SVR12 ≥ 2.0 (p < 0.001). Multivariable analysis identified that M2BPGi levels ≥ 4.0 COI at pretreatment (adjusted hazard ratio [aHR]: 3.33; 95% confidence interval [CI]: 1.54–7.23, p = 0.002) and ≥ 2.0 COI at SVR ₁₂ (aHR: 2.60; 95% CI: 1.16–5.79, p = 0.020) were significantly associated with HCC occurrence in addition to age, sex, liver stiffness measurement (LSM), alanine transaminase (ALT) quotient, and AFP. In conclusion, serum M2BPGi may serve as a valuable biomarker for HCC risk after HCV cure with DAAs.