Predictive Value of Serum Mac‐2 Binding Protein Glycosylation Isomer for Hepatic Fibrosis in Hepatitis C Virus–Infected Patients With Metabolic Dysfunction–Associated Steatotic Liver Disease

Background The diagnostic accuracy and optimal cutoff values of serum Mac‐2 binding protein glycosylation isomer (M2BPGi) for predicting hepatic fibrosis severity in hepatitis C virus (HCV)–infected patients with and without metabolic dysfunction–associated steatotic liver disease (MASLD) remain uncertain. Methods We recruited 2064 patients with available M2BPGi data and valid vibration‐controlled transient elastography (VCTE) results. The areas under the receiver operating characteristic curves (AUROCs) with 95% confidence intervals (CIs) of M2BPGi were compared between MASLD and non‐MASLD groups for fibrosis stages of ≥F2, ≥F3, and F4. M2BPGi cutoff values were determined for the maximal Youden index, positive likelihood ratio (LR+) nearest to ≥10, and negative LR (LR‐) nearest to ≤0.1. Results At the same fibrosis stage, serum M2BPGi levels were significantly higher in MASLD patients than in non‐MASLD patients (F0–F1: 1.12 versus 1.01, p = 0.011; F2: 2.02 versus 1.93, p = 0.013; F3: 3.13 versus 3.08, p = 0.023; F4: 5.32 versus 4.91, p = 0.003). The AUROCs of M2BPGi were comparable between MASLD and non‐MASLD groups for ≥F2 (0.899 [95% CI: 0.878–0.919] versus 0.889 [95% CI: 0.871–0.908]), ≥F3 (0.914 [95% CI: 0.892–0.936] versus 0.934 [95% CI: 0.915–0.952]), and F4 (0.917 [95% CI: 0.894–0.941] versus 0.953 [95% CI: 0.937–0.968]). Optimal cutoff levels for all criteria were higher in patients with MASLD. Conclusions Serum M2BPGi is a reliable marker for assessing hepatic fibrosis severity in HCV patients. However, optimal cutoff values should be adjusted according to MASLD status to improve diagnostic accuracy.