Nature communications · 2024
Development of a novel non-invasive biomarker panel for hepatic fibrosis in MASLD.
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Verschuren Lars, Mak Anne Linde, van Koppen Arianne, Özsezen Serdar, Difrancesco Sonia, Caspers Martien P M, Snabel Jessica, van der Meer David, van Dijk Anne-Marieke, Rashu Elias Badal, Nabilou Puria, Werge Mikkel Parsberg, van Son Koen, Kleemann Robert, Kiliaan Amanda J, Hazebroek Eric J, Boonstra André, Brouwer Willem P, Doukas Michail, Gupta Saurabh, Kluft Cornelis, Nieuwdorp Max, Verheij Joanne, Gluud Lise Lotte, Holleboom Adriaan G, Tushuizen Maarten E, Hanemaaijer Roeland
Аннотация
Accurate non-invasive biomarkers to diagnose metabolic dysfunction-associated steatotic liver disease (MASLD)-related fibrosis are urgently needed. This study applies a translational approach to develop a blood-based biomarker panel for fibrosis detection in MASLD. A molecular gene expression signature identified from a diet-induced MASLD mouse model (LDLr-/-.Leiden) is translated into human blood-based biomarkers based on liver biopsy transcriptomic profiles and protein levels in MASLD patient serum samples. The resulting biomarker panel consists of IGFBP7, SSc5D and Sema4D. LightGBM modeling using this panel demonstrates high accuracy in predicting MASLD fibrosis stage (F0/F1: AUC = 0.82; F2: AUC = 0.89; F3/F4: AUC = 0.87), which is replicated in an independent validation cohort. The overall accuracy of the model outperforms predictions by the existing markers Fib-4, APRI and FibroScan. In conclusion, here we show a disease mechanism-related blood-based biomarker panel with three biomarkers which is able to identify MASLD patients with mild or advanced hepatic fibrosis with high accuracy.