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. 2024 Aug;296(2):177-186.
doi: 10.1111/joim.13813. Epub 2024 Jul 3.

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

Hannes Hegmar  1   2 , Thomas Wiggers  3 , Patrik Nasr  4 , Johan Vessby  5 , Stergios Kechagias  4 , Nils Nyhlin  6 , Hanns-Ulrich Marschall  7 , Åsa Danielsson Borssén  8 , Rickard Strandberg  2 , Morten Karsdal  3 , Diana Julie Leeming  3 , Mattias Ekstedt  4 , Hannes Hagström  1   2
Affiliations
Free article

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

Hannes Hegmar et al. J Intern Med. 2024 Aug.
Free article

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 (age, diabetes, PRO-C3, and platelet 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.

Keywords: MASLD; NAFLD; liver fibrosis; noninvasive tests.

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