Sequential Fibrosis-4 Index and Mac-2 Binding Protein Glycosylation Isomer Combination Improve Detection of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Multicenter Study.

BACKGROUND AND AIMS: The utility of the Mac-2 binding protein glycosylation isomer (M2BPGi) as a noninvasive biomarker for advanced liver fibrosis in metabolic dysfunction3associated steatotic liver disease (MASLD) is unclear. The aim of this study is to evaluate M2BPGi levels in relation to the histopathological features of MASLD and assess its diagnostic performance individually and in combination with the fibrosis-4 (FIB-4) index.

METHODS

A total of 992 patients with biopsy-confirmed MASLD were analyzed. Associations between the M2BPGi levels and histological features were also evaluated.

RESULTS

M2BPGi levels were significantly correlated with steatosis, lobular inflammation, ballooning, and fibrosis stages. Patients with mild steatosis (S0-1) had significantly lower M2BPGi levels than those with severe steatosis (S2-3) (P < .001). Patients with severe inflammation (A2-3) had higher M2BPGi levels than those with mild inflammation (A0-1) (P < .001), and those with advanced ballooning (B2) had significantly higher M2BPGi levels than those with lower grades (B0-1) (P < .001). Advanced fibrosis (F3-4) was associated with higher M2BPGi levels than early-stage fibrosis (F0-2) (P < .001), with a cutoff value of 0.99 (area under the curve [AUC]: 0.774). M2BPGi outperformed the FIB-4 index (AUC: 0.719) and aspartate aminotransferase-to-platelet-ratio index (AUC: 0.665) for the diagnosis of advanced fibrosis (P < .001). A 2-step algorithm combining FIB-4 with M2BPGi reduced the need for further testing by 31.5%, while maintaining a false-negative rate of 13.9%.

CONCLUSION

M2BPGi is a robust biomarker for advanced liver fibrosis in patients with MASLD. Its integration with FIB-4 in screening algorithms enhances diagnostic accuracy while minimizing unnecessary liver biopsies and specialist referrals.