Multicenter evaluation of M2BPGi as a biomarker for liver fibrosis and hepatocellular carcinoma in chronic hepatitis B and C patients in Malaysia

Abstract

Background

Chronic hepatitis B (HBV) and C (HCV) cause major global morbidity, especially in settings with limited diagnostic access. Liver biopsy is not routinely used for fibrosis assessment because of its invasive nature, whereas elastography, a reliable non-invasive alternative, is often limited by high cost. In this context, Mac-2 binding protein glycosylation isomer (M2BPGi) has emerged as a promising non-invasive biomarker for liver fibrosis and hepatocellular carcinoma (HCC), but data from Southeast Asia remain limited. This study assessed its diagnostic accuracy among chronic HBV and HCV patients in Malaysia.

Methods

A cross-sectional study was conducted among 154 participants from seven Malaysian public hospitals: 62 HCV patients, 52 HBV patients, and 40 healthy controls. Liver stiffness was measured using transient elastography, and serum biomarkers (M2BPGi, AFP, FIB-4, GPR) were analyzed. Diagnostic performance for fibrosis, cirrhosis, and HCC was evaluated using ROC curve analysis.

Results

M2BPGi levels, expressed as cutoff index (COI), rose with increasing disease severity, with median values of 0.4 COI (controls), 0.8 COI (non-cirrhotic), 4.9 COI (cirrhotic), and 3.9 COI (HCC) (p < 0.001). For cirrhosis detection, M2BPGi showed excellent accuracy (AUC 0.989; 92% sensitivity; 100% specificity). For HCC screening, it achieved an AUC of 0.962 (85.3% sensitivity; 97.5% specificity). However, it performed poorly in differentiating cirrhosis from HCC (AUC 0.594, p = 0.220).

Conclusion

M2BPGi demonstrates strong diagnostic accuracy for liver fibrosis and cirrhosis in chronic HBV and HCV patients, supporting its use as a non-invasive screening tool. Its limited ability to distinguish HCC from cirrhosis highlights the need for multimodal biomarker strategies and further evaluation in Malaysia.