CLEIA-based type IV collagen 7S for second-step assessment of MRE-defined clinically significant fibrosis in MASLD with indeterminate FIB-4

Stepwise MASLD pathways based on the fibrosis-4 (FIB-4) index leave a large indeterminate subgroup requiring second-step assessment. We evaluated automated chemiluminescent enzyme immunoassay (CLEIA)-based type IV collagen 7S (COL4-7S) as a candidate second-line test for MRE-defined clinically significant fibrosis (≥F2). In this retrospective derivation-validation study, adults with MASLD underwent clinically indicated magnetic resonance elastography (MRE) with serum biomarkers measured within 30 days in a two-center derivation cohort (n=347) and an independent external validation cohort (n=126). COL4-7S was compared with ELF, M2BPGi, and FIB-4 using MRE-defined fibrosis stage (F0-F4). In the derivation cohort, MRE liver stiffness correlated with COL4-7S (r=0.59), ELF (r=0.58), M2BPGi (r=0.62), and FIB-4 (r=0.49; all p<0.001), with similar ordinal discrimination across F0-F4. Within the indeterminate FIB-4 range, second-step COL4-7S correctly classified 90/136 patients (66%) for MRE-defined ≥F2; ELF and M2BPGi correctly classified 90/136 (66%) and 73/136 (54%), respectively. In external validation, COL4-7S and ELF correctly classified 32/50 (64%) and 34/50 (68%) patients, respectively. These findings indicate numerically similar second-step performance of CLEIA-based COL4-7S and ELF for MRE-defined ≥F2 fibrosis in this retrospective cohort. Prospective studies are needed to determine whether COL4-7S improves workflow, cost-effectiveness, and patient outcomes in routine MASLD pathways.