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

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.