Mac-2 Binding Protein Glycosylation Isomer (M2BPGi): A Novel Biomarker for Liver Fibrosis and Hepatocellular Carcinoma

Authors

  • Hind Fawzi Aref University of Fallujah, College of applied sciences

Keywords:

Mac-2 Binding Protein Glycosylation Isomer (M2BPGi), Liver fibrosis, Hepatocellular carcinoma, Chronic liver disease, Non-invasive biomarker

Abstract

Chronic liver disease remains a major global health challenge and is a leading cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Early identification of progressive fibrosis is essential for timely therapeutic intervention and improved clinical outcomes; however, liver biopsy remains invasive and is unsuitable for repeated monitoring. Consequently, considerable attention has been directed toward the development of reliable non-invasive biomarkers. Mac-2 Binding Protein Glycosylation Isomer (M2BPGi), also known as Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP), has emerged as one of the most promising biomarkers for assessing liver fibrosis across a wide spectrum of chronic liver diseases, including viral hepatitis, metabolic dysfunction-associated steatotic liver disease, alcoholic liver disease, and autoimmune liver disorders. Increasing evidence indicates that circulating M2BPGi levels correlate closely with histological fibrosis stage, hepatic inflammation, portal hypertension, and liver functional reserve. Moreover, elevated M2BPGi concentrations have been associated with an increased risk of hepatocellular carcinoma development, postoperative recurrence, and poor clinical prognosis, highlighting its value beyond fibrosis assessment. Recent studies have also demonstrated the utility of M2BPGi in monitoring disease progression, evaluating treatment response, and improving risk stratification when combined with established clinical scoring systems and imaging modalities. This review summarizes the biological basis of M2BPGi, its molecular mechanisms, diagnostic and prognostic performance, and current clinical applications in chronic liver disease and hepatocellular carcinoma. The advantages, limitations, and future perspectives of integrating M2BPGi into routine clinical practice are also discussed. Overall, current evidence supports M2BPGi as a highly promising non-invasive biomarker that may facilitate early diagnosis, individualized patient management, and improved long-term outcomes in patients with chronic liver disease and hepatocellular carcinoma.

References

M. Hiyoshi et al., “Usefulness of Serum Mac-2 Binding Protein Glycosylation Isomer in Patients Undergoing Hepatectomy: A Case Controlled Study,” Annals of Medicine and Surgery, vol. 48, pp. 17–22, 2019.

N. Tamaki, M. Kurosaki, R. Loomba, and N. Izumi, “Clinical Utility of Mac-2 Binding Protein Glycosylation Isomer in Chronic Liver Diseases,” Annals of Laboratory Medicine, vol. 41, no. 1, pp. 16–24, 2021.

I.-C. Lee et al., “M2BPGi Correlated with Immunological Biomarkers and Further Stratified Recurrence Risk in Patients with Hepatocellular Carcinoma,” Liver Cancer, vol. 14, no. 1, pp. 68–79, 2025.

P.-C. Lee et al., “Serum Fibrosis Marker M2BPGi-Based Novel Score Predicts Survival of Unresectable HCC Undergoing Immunotherapy,” JHEP Reports, 2025.

M. Sotoudeheian, “Value of Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) in Assessing Liver Fibrosis in Metabolic Dysfunction-Associated Liver Disease: A Comprehensive Review of Its Serum Biomarker Role,” Current Protein & Peptide Science, vol. 26, no. 1, pp. 6–21, 2025.

T.-C. Tseng et al., “Expert Consensus on Clinical Usefulness of M2BPGi for Managing Chronic Liver Diseases,” Journal of the Formosan Medical Association, 2025.

A. Beaufrère et al., “Gene Expression Signature as a Surrogate Marker of Microvascular Invasion on Routine Hepatocellular Carcinoma Biopsies,” Journal of Hepatology, vol. 76, no. 2, pp. 343–352, 2022.

N. Ishii et al., “Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Increases in Patients with Obstructive Jaundice through the Activation of Hepatic Stellate Cells by Bile Acids,” Hepatology Research, 2025.

C.-H. Liu et al., “Serum Mac-2 Binding Protein Glycosylation Isomer to Predict the Severity of Hepatic Fibrosis in Patients with Hepatitis C Virus Infection,” Diagnostics, vol. 12, no. 11, Art. no. 2650, 2022.

S. Gong et al., “Evaluation of Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) as a Diagnostic Marker for Staging Liver Fibrosis: A Meta-Analysis,” PeerJ, vol. 12, Art. no. e17658, 2024.

Y. Kamada et al., “Utility of Mac-2 Binding Protein Glycosylation Isomer as an Excellent Biomarker for the Prediction of Liver Fibrosis, Activity, and Hepatocellular Carcinoma Onset: An Expert Review,” Journal of Gastroenterology, 2025.

L.-Y. Mak et al., “Role of Serum M2BPGi Levels on Diagnosing Significant Liver Fibrosis and Cirrhosis in Treated Patients with Chronic Hepatitis B Virus Infection,” Clinical and Translational Gastroenterology, vol. 9, Art. no. 163, 2018.

M. Romańczyk et al., “Non-Invasive Markers for the Detection of Gastric Precancerous Conditions,” Cancers, vol. 16, 2024.

M. Dameri, “Non-Invasive Biomarkers in Breast Cancer Early Diagnosis,” 2025.

E. Huang et al., “Diagnostic Potential of Minimally Invasive Biomarkers: A Biopsy-Centered Viewpoint from the Banff Minimally Invasive Diagnostics Working Group,” American Journal of Transplantation, 2022.

H.-K. Chan et al., “Multicenter Evaluation of M2BPGi as a Biomarker for Liver Fibrosis and Hepatocellular Carcinoma in Chronic Hepatitis B and C Patients in Malaysia,” Advances in Biomarker Sciences and Technology, 2026.

H. Uojima et al., “Quantitative Measurements of M2BPGi Depend on Liver Fibrosis and Inflammation,” Journal of Clinical and Experimental Hepatology, 2024.

K. Hagiwara et al., “A New Liver Regeneration Molecular Mechanism Involving Hepatic Stellate Cells, Kupffer Cells, and Glucose-Regulated Protein 78 as a New Hepatotrophic Factor,” Journal of Hepato-Biliary-Pancreatic Sciences, 2023.

T. Ueno et al., “Changes in Serum Mac-2 Binding Protein Glycosylation-Modified Isomer (M2BPGi) during Follow-Up of Intestinal Failure Patients without Intestinal Failure-Associated Liver Disease,” Pediatric Surgery International, 2022.

A. A. E. Othman et al., “Circulating HBcrAg, miRNA-122, and M2BPGi as Predictive Biomarkers for Hepatocellular Carcinoma in Chronic Hepatitis B Patients: A Case-Control Study,” Iranian Journal of Medical Sciences, 2026.

K. R. Stephens et al., “Mac-2 Binding Protein Glycosylation Isomer as a Novel Serum Biomarker for Recurrence in Hepatocellular Carcinoma,” World Journal of Gastroenterology, vol. 32, no. 5, 2026.

Y.-P. Chang et al., “Serum Mac-2 Binding Protein Glycosylation Isomer in Predicting Hepatocellular Carcinoma Occurrence among Patients with Direct-Acting Antiviral-Induced HCV Cure,” Scientific Reports, 2026.

S. Takakusagi et al., “Impact of M2BPGi on the Hepatocarcinogenesis after the Combination Therapy with Daclatasvir and Asunaprevir for Hepatitis C,” Internal Medicine, vol. 60, no. 3, pp. 393–401, 2021.

A. C. Mackinnon et al., “Galectin-3: Therapeutic Targeting in Liver Disease,” Expert Opinion on Therapeutic Targets, 2023.

Y. Kamada et al., “SWOT Analysis of Noninvasive Tests for Diagnosing NAFLD with Severe Fibrosis: An Expert Review by the JANIT Forum,” Journal of Gastroenterology, 2023.

X. Xu et al., “Advanced Fabrication of Three-Dimensional Bicontinuous MXene/Agarose Composite Monoliths for High-Selective Rapid Separation of Antibodies,” Chemical Engineering Journal, 2025.

I. Kiss et al., “Hepatic Lipoprotein Metabolism: Current and Future In Vitro Cell-Based Systems,” Biomolecules, vol. 15, 2025.

X. Liu et al., “The Value of Serum Mac-2 Binding Protein Glycosylation Isomer in the Diagnosis of Liver Fibrosis: A Systematic Review and Meta-Analysis,” Frontiers in Physiology, vol. 15, Art. no. 1382293, 2024.

S. M. M. Farag et al., “Mac-2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients with Chronic Hepatitis B or C Infection,” Egyptian Journal of Medicine, 2024.

N. Harimoto et al., “Mac-2 Binding Protein Glycosylation Isomer as a Prognostic Marker for Hepatocellular Carcinoma with Sustained Virological Response,” Anticancer Research, vol. 42, no. 7, pp. 3549–3556, 2022.

R. Choi et al., “Intraindividual Changes in Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Performed in Korean Subjects,” Clinical Laboratory, vol. 68, no. 7, 2022.

M. Szapacs et al., “AAPS New Advances in Biomarker Research: M10 BMV Guideline and Global Harmonization; Hybrid Assays; Oligonucleotides and ADC; Non-Liquid and Rare Matrices; Regulatory Inputs,” Bioanalysis, vol. 15, no. 17, 2023.

M. A. Bestari et al., “Revisiting Mac-2-Binding Protein Glycosylation Isomer (M2BPGi) for Diagnosing High-Risk Liver Fibrosis in Chronic Hepatitis B Patients: A Stepwise Diagnostic Approach,” Journal of Clinical and Translational Hepatology, 2024.

H. Park, D. W. Jun, H. K. Park, and M. Kim, “Clinical Implications of Serum Mac-2-Binding Protein Glycan Isomer as a Novel Biomarker of Advanced Hepatic Fibrosis in Diabetes,” Annals of Translational Medicine, vol. 8, no. 23, Art. no. 1583, 2020.

L.-Y. Mak et al., “Role of Serum M2BPGi Levels in Predicting Persistence of Advanced Fibrosis in Chronic Hepatitis B Virus Infection,” Digestive Diseases and Sciences, 2022.

H. H. Bui et al., “Evaluating M2BPGi as a Marker for Liver Fibrosis in Patients with Chronic Hepatitis B,” Digestive Diseases and Sciences, vol. 68, pp. 4093–4102, 2023.

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Published

2026-06-21

How to Cite

Aref, H. F. (2026). Mac-2 Binding Protein Glycosylation Isomer (M2BPGi): A Novel Biomarker for Liver Fibrosis and Hepatocellular Carcinoma. Central Asian Journal of Medical and Natural Science, 7(3), 639–648. Retrieved from https://cajmns.casjournal.org/index.php/CAJMNS/article/view/3321

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