Performance of novel collagen turnover biomarkers to detect increased liver stiffness in MASLD

Abstract Background Cleavage products from collagen formation and degradation hold potential as first‐line biomarkers for the risk of advanced fibrosis in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD). Here, we evaluated the performance of PRO‐C3, PRO‐C6, C4M, PRO‐C18L, and the clinical score ADAPT ( a ge, d i a betes, P RO‐C3, and pla t elet count) to detect patients with an LSM >8 kPa or >12 kPa in comparison to the Fibrosis‐4 Index (FIB‐4). Methods Serum from patients with MASLD ( n = 269) from six Swedish University Hospitals was analyzed using enzyme‐linked immunosorbent assay‐based methods. Liver stiffness measurement (LSM) by vibration‐controlled transient elastography was performed. The area under the curve (AUC), calibration curves, and net benefit analysis were used. Results An LSM >8 kPa was found in 108 (40.1%) patients. PRO‐C3, PRO‐C6, C4M, and PRO‐C18L had AUCs ranging from 0.48 to 0.62. ADAPT had the highest AUC (0.73, 95% confidence interval [CI] = 0.67–0.79) to detect patients >8 kPa, compared to FIB‐4 (0.71, (95%CI = 0.64–0.77, p = 0.35), and had a higher net benefit compared to FIB‐4 from a probability threshold of 15%. FIB‐4 and ADAPT performed equally well to detect patients with an LSM >12 kPa, AUC 0.76 versus 0.76, p = 0.93. Conclusions ADAPT seems to be marginally better than FIB‐4 in identifying patients with an LSM >8 kPa. However, the clinical utility of ADAPT as a first line test is uncertain, especially in low‐risk populations. The overall performance of FIB‐4 was similar to that of ADAPT in detecting patients with an LSM of >12 kPa. Altogether, the results suggest that ADAPT might be useful to detect earlier stages of fibrosis in MASLD, but that FIB‐4 remains a first‐line test for advanced fibrosis.