Development of a novel non-invasive biomarker panel for hepatic fibrosis in MASLD
Lars Verschuren, Anne Linde Mak, Arianne van Koppen, Serdar Özsezen, Sonia Difrancesco, Martien P. M. Caspers, Jessica Snabel, David van der Meer, Anne‐Marieke van Dijk, Elias B. Rashu, Puria Nabilou, Mikkel Werge, Koen C. van Son, Robert Kleemann, Amanda J. Kiliaan, Eric J. Hazebroek, André Boonstra, Willem Pieter Brouwer, Michail Doukas, Saurabh Gupta, Cornelis Kluft, Max Nieuwdorp, Joanne Verheij, Lise Lotte Gluud, Adriaan G. Holleboom, Maarten E. Tushuizen, Roeland Hanemaaijer
Abstract
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.