Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2019; 25(11): 1398-1408
Published online Mar 21, 2019. doi: 10.3748/wjg.v25.i11.1398
Serum Mac-2 binding protein glycosylation isomer level predicts hepatocellular carcinoma development in E-negative chronic hepatitis B patients
Lung-Yi Mak, Wai-Pan To, Danny Ka-Ho Wong, James Fung, Fen Liu, Wai-Kay Seto, Ching-Lung Lai, Man-Fung Yuen
Lung-Yi Mak, Wai-Pan To, James Fung, Department of Medicine, Queen Mary Hospital, Hong Kong, China
Danny Ka-Ho Wong, Fen Liu, Wai-Kay Seto, Ching-Lung Lai, Man-Fung Yuen, Department of Medicine, The University of Hong Kong, Hong Kong, China
Danny Ka-Ho Wong, James Fung, Wai-Kay Seto, Ching-Lung Lai, Man-Fung Yuen, State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
Author contributions: Mak LY and To WP were involved in drafting the manuscript. Wong DKH was involved in performing laboratory tests and collecting the data. Fung J was involved in data acquisition, statistical analysis, and language editing of the manuscript. Seto WK was involved in interpretation of the data and critical revision of the manuscript. Lai CL was involved in critical revision of the manuscript. Yuen MF was involved in study concept and design, analysis and interpretation of data, critical revision of manuscript, and overall study supervision. All authors have approved the final draft submitted.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board/ Ethics Committee of the University of Hong Kong and the Hong Kong West Cluster of Hospital Authority.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data and stored serum samples that were obtained after each patient agreed to such storage for clinical research by informed consent in previous studies.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Man-Fung Yuen, DSc, FRCP (C), MBBS, MD, MRCP, PhD, Professor, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road 102, Hong Kong, China.
Telephone: +86-852-22553994 Fax: +86-852-28162863
Received: December 15, 2018
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.

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

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.