Serum Mac-2-binding protein glycosylation isomer and risk of hepatocellular carcinoma in entecavir-treated chronic hepatitis B patients

J Gastroenterol Hepatol. 2019 Oct;34(10):1817-1823. doi: 10.1111/jgh.14637. Epub 2019 Mar 10.

Abstract

Background and aim: Hepatocellular carcinoma (HCC) can still develop in chronic hepatitis B (CHB) patients receiving antiviral treatment. Serum Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis. We investigated its role on incidence of HCC in entecavir (ETV)-treated CHB patients.

Methods: We identified HCC cases diagnosed at ≥ 1 year of ETV treatment. CHB patients without HCC (matched for age, gender, baseline hepatitis B virus-DNA, and duration of ETV treatment) were identified in approximately 1:2 ratio (HCC: non-HCC) for comparison. Serum samples were retrieved at baseline (initiation of ETV), 3, and 5 years of ETV for serum M2BPGi measurement (expressed in cut-off index [COI]).

Results: One hundred HCC cases were matched with 185 CHB patients without HCC (median age 56.7 years, 78.9% male, baseline hepatitis B virus-DNA 5.6 logIU/mL, and median follow-up 7.1 years). Median time from ETV initiation to incident HCC was 3.9 years. Serum M2BPGi levels were significantly higher in HCC cases compared with controls at baseline and year 3 (1.25 vs 0.98 [P = 0.004], 0.89 vs 0.74 [P = 0.018] COI, respectively). Multivariate analysis showed that baseline M2BPGi was the only independent factor associated with incident HCC (odds ratio 1.241, 95% confidence interval 1.039-1.482, P = 0.017). Using a cut-off value of 1.15 COI, the sensitivity, specificity, positive predictive value, and negative predictive value of baseline serum M2BPGi in cirrhotic patients to predict incident HCC were 90%, 53.8%, 69.6%, and 82.1%, respectively.

Conclusions: Baseline and 3-year serum M2BPGi may be useful to identify high risk patients on antiviral treatment for subsequent HCC development.

Keywords: M2BPGi; biomarker; chronic hepatitis B; entecavir; hepatocellular carcinoma.

MeSH terms

  • Antigens, Neoplasm / blood*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / epidemiology
  • Hepatitis B, Chronic / virology
  • Hong Kong / epidemiology
  • Humans
  • Incidence
  • Liver Neoplasms / blood
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / virology
  • Male
  • Membrane Glycoproteins / blood
  • Middle Aged
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • Antiviral Agents
  • Biomarkers
  • Biomarkers, Tumor
  • LGALS3BP protein, human
  • Membrane Glycoproteins
  • TAA90K protein, human
  • entecavir
  • Guanine