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

World J Gastroenterol. 2019 Mar 21;25(11):1398-1408. doi: 10.3748/wjg.v25.i11.1398.

Abstract

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 (M2BPGi) is a novel serological marker for fibrosis. The role of M2BPGi in prediction of HCC is unknown.

Aim: To examine the role of serum M2BPGi 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 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.

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 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.

Conclusion: High serum M2BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC development in treatment-naive HBeAg-negative CHB patients.

Keywords: Biomarker; Hepatitis B; Hepatocellular carcinoma; Liver fibrosis; Mac-2 binding protein glycosylation isomer.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Antigens, Neoplasm / blood*
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / pathology
  • Carrier Proteins / blood*
  • Carrier Proteins / metabolism
  • Female
  • Follow-Up Studies
  • Glycoproteins / blood*
  • Glycoproteins / metabolism
  • Glycosylation
  • Hepatitis B e Antigens / immunology
  • Hepatitis B e Antigens / isolation & purification
  • Hepatitis B virus / immunology
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / pathology
  • Hepatitis B, Chronic / virology
  • Humans
  • Incidence
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Protein Isoforms / blood
  • Protein Isoforms / metabolism
  • ROC Curve
  • Retrospective Studies
  • Seroconversion

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Carrier Proteins
  • Glycoproteins
  • Hepatitis B e Antigens
  • LGALS3BP protein, human
  • Protein Isoforms