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Development of a novel non-invasive biomarker panel for hepatic fibrosis in MASLD

Author

Listed:
  • Lars Verschuren

    (TNO Healthy Living & Work)

  • Anne Linde Mak

    (Amsterdam University Medical Centers)

  • Arianne Koppen

    (TNO Healthy Living & Work)

  • Serdar Özsezen

    (TNO Healthy Living & Work)

  • Sonia Difrancesco

    (TNO Healthy Living & Work)

  • Martien P. M. Caspers

    (TNO Healthy Living & Work)

  • Jessica Snabel

    (TNO Healthy Living & Work)

  • David Meer

    (GenomeScan)

  • Anne-Marieke Dijk

    (Amsterdam University Medical Centers)

  • Elias Badal Rashu

    (University of Copenhagen)

  • Puria Nabilou

    (University of Copenhagen)

  • Mikkel Parsberg Werge

    (University of Copenhagen)

  • Koen Son

    (Amsterdam University Medical Centers)

  • Robert Kleemann

    (TNO Healthy Living & Work)

  • Amanda J. Kiliaan

    (Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behavior)

  • Eric J. Hazebroek

    (Wageningen University)

  • André Boonstra

    (Erasmus MC University Medical Center)

  • Willem P. Brouwer

    (Erasmus MC University Medical Center)

  • Michail Doukas

    (Erasmus MC Cancer Institute)

  • Saurabh Gupta

    (Bristol Meyers Squibb)

  • Cornelis Kluft

    (Good Biomarker Sciences)

  • Max Nieuwdorp

    (Amsterdam University Medical Centers)

  • Joanne Verheij

    (Amsterdam University Medical Centers)

  • Lise Lotte Gluud

    (University of Copenhagen)

  • Adriaan G. Holleboom

    (Amsterdam University Medical Centers)

  • Maarten E. Tushuizen

    (Leiden University Medical Center)

  • Roeland Hanemaaijer

    (TNO Healthy Living & Work)

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.

Suggested Citation

  • Lars Verschuren & Anne Linde Mak & Arianne Koppen & Serdar Özsezen & Sonia Difrancesco & Martien P. M. Caspers & Jessica Snabel & David Meer & Anne-Marieke Dijk & Elias Badal Rashu & Puria Nabilou & M, 2024. "Development of a novel non-invasive biomarker panel for hepatic fibrosis in MASLD," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48956-0
    DOI: 10.1038/s41467-024-48956-0
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