Liver fibrosis severity evaluated by shear-wave elastography is associated with procoagulant and systemic inflammatory activity in patients with cirrhosis

George Kalambokis; Nikolaos Aggelis; Ilias Tsiakas; Dimitrios Biros; Grigorios Despotis; Evangelia Papapetrou; Christina Tsaousi; Georgios S. Markopoulos; Georgios Kolios; Reveka Konstantopoulou; Stavroula Tsiara; Gerasimos Baltayiannis; Haralampos Milionis

Authors George Kalambokis, Nikolaos Aggelis, Ilias Tsiakas, Dimitrios Biros, Grigorios Despotis, Evangelia Papapetrou, Christina Tsaousi, Georgios S. Markopoulos, Georgios Kolios, Reveka Konstantopoulou, Stavroula Tsiara, Gerasimos Baltayiannis, Haralampos Milionis.

Abstract

Background Hemostatic and inflammatory pathways may drive liver fibrogenesis. We investigated whether coagulation and systemic inflammatory activities influence liver fibrosis severity in patients with cirrhosis and thrombocytopenia.

Methods Two patient groups were evaluated according to liver stiffness measurement (LSM) through shear wave elastography: ≥25 kPa (n=100) vs. <25 kPa (n=100). Anti-hemostatic parameters (platelet count, factors II, V, VII, IX, X, XI, XII, and XIII, fibrinogen, and a2-antiplasmin), pro-hemostatic parameters (factor VIII [FVIII], protein C [PC], protein S, antithrombin, von Willebrand factor-antigen [vWf-Ag], plasminogen, and plasminogen activator inhibitor-1), the FVIII-to-PC ratio as procoagulant imbalance index, and systemic inflammation markers (serum lipopolysaccharide-binding protein [LBP], tumor necrosis factor [TNF]-α, and interleukin [IL]-6) were measured. Cirrhosis severity was evaluated by model for end-stage liver disease (MELD) score.

Results Patients with LSM≥25 kPa exhibited significantly higher decompensation rates, MELD score, FVIII-to-PC ratio, and levels of FVIII, PC, protein S, vWf-Ag, LBP, TNF-α, and IL-6, and significantly lower levels of anti-hemostatic parameters than those with LSM<25 kPa. In multivariate analysis evaluating coagulation parameters alone or alongside inflammatory markers, FVIII-to-PC ratio (P=0.01/P=0.03) and LBP (P=0.01) were linked to LSM≥25 kPa after adjusting for MELD score and prior decompensation. LSM correlated significantly with FVIII-to-PC ratios, and levels of FVIII, PC, vWf-Ag, LBP, TNF-α and IL-6, in both the total cohort and patients with LSM≥25 kPa. LBP, TNF-α and IL-6 levels correlated significantly with the FVIII-to-PC ratios and vWf-Ag levels in both LSM subgroups.

Conclusion Higher procoagulant and systemic inflammatory activities are associated with greater liver fibrosis severity in cirrhotic patients.

Keywords Liver fibrosis, cirrhosis, systemic inflammation, prothrombotic activity, shear wave elastography

Ann Gastroenterol 2026; 39 (3): 310-318