Serum Mac-2 binding protein glycosylation isomer level predicts hepatocellular carcinoma development in E-negative chronic hepatitis B patients

摘要

BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for fibrosis. The role of M2 BPGi in prediction of HCC is unknown.AIM To examine the role of serum M2 BPGi in predicting HCC development in hepatitis B e antigen(HBeAg)-negative patients.METHODS Treatment-naive CHB patients with documented spontaneous HBeAg seroconversion were recruited. Serum M2 BPGi was measured at baseline(within3 years from HBeAg seroconversion), at 5 years and 10 years after HBeAg seroconversion and expressed as cut-off index(COI). Multivariate cox regression was performed to identify predictors for HCC development. ROC analysis was used to determine the cut-off value of M2 BPGi.RESULTS Among 207 patients(57% male, median age at HBeAg seroconversion 40 years old) with median follow-up of 13.1(11.8-15.5) years, the cumulative incidence of HCC at 15 years was 7%. Median M2 BPGi levels were significantly higher in patients with HCC compared to those without HCC(baseline: 1.39 COI vs 0.38 COI, P < 0.001; 5-year: 1.45 COI vs 0.47 COI, P < 0.001; 10-year: 1.20 COI vs 0.55 COI, P = 0.001). Multivariate analysis revealed age at HBeAg seroconversion[odds ratio(OR) = 1.196, 95% confidence interval(CI): 1.034-1.382, P = 0.016] and baseline M2 BPGi(OR = 4.666, 95%CI: 1.296-16.802, P = 0.018) were significant factors predictive of HCC. Using a cut-off value of 0.68 COI, baseline M2 BPGi yielded AUROC of 0.883 with 91.7% sensitivity and 80.8% specificity.CONCLUSION High serum M2 BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC development in treatment-naive HBeAg-negative CHB patients.