Von Willebrand Factor (VWF) propeptide levels are similarly accurate for assessing portal hypertension as compared to VWF antigen

Background & Aims Endothelial dysfunction is an important mechanism contributing to portal hypertension (PH) in advanced chronic liver disease (ACLD) and is reflected by increased von Willebrand factor antigen (VWF-Ag) levels. This study aimed to elucidate VWF-release (by measuring its propeptide; VWF-N) and -cleavage (by measuring its ADAMTS13-processed form; VWF-A) as well as their association with PH severity.

Methods Levels of VWF-Ag and VWF-N/VWF-A were assessed in 229 patients with ACLD (hepatic venous pressure gradient [HVPG] ≥6mmHg) undergoing HVPG measurement in the absence of bacterial infections or acute decompensation. Furthermore, ADAMTS13 activity (ADAMTS13-Act; the main VWF-cleaving protease) and VWF activity (VWF-Act) were analysed in a subgroup of patients (n = 166).

Results VWF-Ag levels significantly correlated with HVPG (Spearman’s ρ=0.374, p<0.001), similar to VWF-N (ρ=0.334, p<0.001). VWF-N was strongly associated with VWF-Ag (ρ=0.627, p<0.001), whereas VWF-A exhibited weak correlations with VWF-Ag (ρ=0.207, p = 0.002) and HVPG (ρ=0.181, p = 0.006). VWF-Ag and VWF-N were similarly accurate for identification of clinically significant PH (HVPG ≥10mmHg; AUROC 0.804 for VWF-Ag; 0.768 for VWF-N; both p<0.001). Interestingly, ADAMTS13-Act was not associated with PH severity or disease stage, and exhibited no significant correlation with VWF-Ag, VWF-N, and VWF-A (Figure), respectively. VWF-Act strongly reflected VWF-Ag levels (ρ=0.874, p<0.001), but showed comparatively weak association with VWF-A (ρ=0.297, p<0.001). VWF-Act/-Ag ratio was not linked to PH or disease stage, but correlated negatively with ADAMTS13 activity (ρ= -0.256, p<0.001).

Conclusion In patients with ACLD, VWF-Ag levels and its propeptide are more suitable surrogates of PH than ADAMTS13-cleaved VWF-A. ADAMTS13-Act is not related to disease severity under clinically stable conditions and VWF-A levels are rather dependent on the amount of circulating VWF than ADAMTS13-Act. VWF-Ag levels reflect VWF-Act in vitro, but VWF-Act appears to be decreased with increasing ADAMTS13-Act.

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Publication History

Article published online:
01 September 2021