Published online Mar 21, 2019. doi: 10.3748/wjg.v25.i11.1398
Peer-review started: December 17, 2018
First decision: January 6, 2019
Revised: January 22, 2019
Accepted: January 26, 2019
Article in press: January 26, 2019
Published online: March 21, 2019
Liver cirrhosis is a major risk factor for hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB). Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serological marker for fibrosis. The role of M2BPGi in prediction of HCC is unknown.
To examine the role of serum M2BPGi in predicting HCC development in hepatitis B e antigen (HBeAg)-negative patients.
Treatment-naive CHB patients with documented spontaneous HBeAg seroconversion were recruited. Serum M2BPGi was measured at baseline (within 3 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 M2BPGi.
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 M2BPGi 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 M2BPGi (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 M2BPGi yielded AUROC of 0.883 with 91.7% sensitivity and 80.8% specificity.
High serum M2BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC development in treatment-naive HBeAg-negative CHB patients.
Core tip: Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel marker to assess severity of liver disease. The aim of this study was to assess its role in prediction of incident hepatocellular carcinoma (HCC) in patients with chronic hepatitis B who were prospectively followed-up for a median duration of 13.1 years. High serum M2BPGi increased HCC risk by 4-5 folds. If M2BPGi is below the threshold (0.68 cut-off index), there is > 99% chance that the patient will not develop liver cancer in the subsequent 15 years.