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Updated: Jun 4, 2026

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Fibroblast activation protein and down-stream effects on its substrates in metabolic dysfunction-associated steatotic
Sara F Hansson1, Patrik Nasr2,3, Jane Knöchel4
1Translational Science and Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Background:
Fibroblast activation protein (FAP) is a serine protease upregulated in liver and blood in patients with chronic liver disease of several etiologies. FAP has a pro-fibrotic effect and may also regulate disease progression by proteolytically affecting two circulating substrates, fibroblast growth factor 21 (FGF21) and α2-antiplasmin (α2AP). The aim of this study was to investigate the involvement of FAP in metabolic dysfunction-associated steatotic liver disease (MASLD).
Methods:
FAP protein levels were measured in liver biopsies (n = 47) and plasma samples (n = 79) from an extensively characterized longitudinal MASLD cohort. FAP-cleaved and -uncleaved forms of α2AP were measured with a novel mass spectrometry-based method, using isotopically labeled recombinant protein fragments as internal standards. Total and intact FGF21 levels were quantified using ELISA. Results were correlated to histopathological steatosis grade, inflammation grade, ballooning grade and fibrosis stage.
Results:
Both liver and plasma levels of FAP were increased in patients with advanced fibrosis, stage 3-4 vs 0-2 (p < 0.005) but were not affected by steatosis grade. The fraction of FAP-cleaved α2AP correlated with the plasma FAP level and was significantly higher in patients with fibrosis stage 3-4 (p < 0.05). In contrast, plasma FAP did not correlate with the ratio of intact FGF21.
Conclusion:
These results show that FAP expression is increased in more advanced hepatic fibrosis. This suggests that FAP might be involved in the pathophysiology of MASLD progression and could be a biomarker for advanced hepatic fibrosis. Studies in larger prospective cohorts are needed to confirm these findings.
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