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

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.