Georg Kramer, Irina Andreea Lie-Ungurean, Benedikt Silvester Hofer, Lukas Hartl, Mathias Jachs, Lorenz Balcar, Georg Semmler, Christian Sebesta, Paul Thöne, Marlene Hintersteininger, Paula Höfinger, Rodrig Marculescu, Thomas Perkmann, Philipp Schwabl, Michael Trauner, Mattias Mandorfer, Thomas Reiberger, Benedikt Simbrunner
Circulating fibronectin reflects hepatic synthetic capacity and matrix remodeling. Its divergent exploratory associations with variceal bleeding and portal vein thrombosis suggest that fibronectin may capture aspects of hemostatic vulnerability.
BACKGROUND AND AIMS: Fibronectin is a multifunctional matrix glycoprotein involved in tissue remodeling and hemostasis; however, its clinical relevance in cirrhosis remains unclear. This study characterized circulating fibronectin across stages of advanced chronic liver disease (ACLD) and assessed its correlation to pathophysiological biomarkers and predictive value for liver-related complications.
METHODS: Patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled with circulating fibronectin measured simultaneously. Associations were assessed using correlation analyses and systems modeling. Competing-risk regression was used to evaluate clinical outcomes.
RESULTS: Among 298 patients (median HVPG 17 [12-21] mmHg; MELD 3.0 12 [9-17]), fibronectin levels were lower in decompensated than compensated ACLD (30.3 vs. 38.8 mg/dL; p < 0.001). Fibronectin correlated with hepatic synthesis (cholinesterase: Spearman's r = 0.64) and MELD 3.0 (r = - 0.47; both p < 0.001) while showing an independent positive association with ELF (β = 0.19; p < 0.001). In systems modeling, hepatic synthesis explained most of fibronectin variance (cholinesterase: 37%), followed by fibrinolysis (antiplasmin: 14%) and matrix remodeling (ELF: 12%). In exploratory analyses, higher fibronectin levels were independently associated with variceal bleeding (aSHR 1.04, p = 0.017), and lower fibronectin levels with portal vein thrombosis (aSHR 0.95, p = 0.031), when adjusted for HVPG, MELD 3.0, or IL-6. Fibronectin was not associated with other hepatic decompensation events, hepatocellular carcinoma, or liver-related mortality.
CONCLUSION: Circulating fibronectin reflects hepatic synthetic capacity and matrix remodeling. Its divergent exploratory associations with variceal bleeding and portal vein thrombosis suggest that fibronectin may capture aspects of hemostatic vulnerability.
CLINICAL TRIAL NUMBER: NCT03267615.