Non-selective betablockers (NSBB) exert beneficial effects beyond lowering hepatic venous pressure gradient (HVPG), which may be particularly relevant in patients with decompensated cirrhosis (DC), in whom bacterial translocation and -induced systemic inflammation drive the development of complications such as acute-on-chronic liver failure (ACLF). We evaluated whether NSBB-related changes in von Willebrand factor (VWF) may serve as a biomarker for these effects.
In this retrospective analysis, 159 prospectively characterized patients with clinically stable DC (i.e. without acute decompensation) who underwent paired HVPG/VWF assessments before/on NSBB-therapy were classified as ‘VWF-responders’ (as defined by a ≥5%-decrease in VWF)/’VWF-non-responders’.
There were no major differences in baseline characteristics between VWF-responders (61%)/VWF-non-responders. VWF-responders showed more pronounced decreases in inflammation (procalcitonin), while rates of HVPG-response were similar. In line, NSBB-related changes in VWF correlated with the dynamics of bacterial translocation/inflammation (lipopolysaccharide-binding protein, C-reactive protein, and procalcitonin), rather than those of HVPG. Interestingly, VWF-responders also showed less pronounced NSBB-related decreases in mean arterial pressure, suggesting an amelioration of systemic vasodilatation. Finally, VWF-response was associated with decreased risks of further decompensation (adjusted hazard ratio[aHR]:0.555[95%CI:0.337-0.912];p=0.020), ACLF (aHR:0.302[95%CI:0.126-0.721];p=0.007), and liver-related death (aHR:0.332[95%CI:0.179-0.616];p<0.001) in Cox-regression models adjusted for prognostic factors including changes in HVPG.
Decreases in VWF upon NSBB-therapy reflect their anti-inflammatory activity, are accompanied by less pronounced adverse effects on systemic hemodynamics, and are independently associated with a decreased risk of further decompensation, ACLF, and death. VWF-response may discriminate between decompensated patients who benefit from NSBB-treatment and have a favourable prognosis vs. patients with poor outcomes.

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.