NSBB-associated VWF-decreases in decompensated cirrhosis indicate a reduced risk of further decompensation, ACLF, and death

Background and Aims Bacterial translocation promotes endothelial dysfunction and systemic inflammation (SI), thereby driving disease progression in cirrhosis. Non-selective beta-blockers (NSBBs) may exert beneficial effects beyond lowering portal pressure.We assessed (i) NSBB-related changes in von Willebrand factor levels (VWF) and (ii) their prognostic value for outcomes in decompensated cirrhosis.

Method We assessed changes in VWF as a surrogate marker for endothelial dysfunction, as well as biomarkers of SI (C-reactive protein[CRP], procalcitonin[PCT]) and of hemodynamic derangement (mean arterial pressure [MAP]) in patients with stable decompensated cirrhosis undergoing paired hepatic venous pressure gradient (HVPG) measurements before and under NSBB treatment. Patients were followed until last clinical contact, the occurrence of risk-modifying events (antiviral therapy, alcohol abstinence, or hepatocellular carcinoma), liver transplantation, or death. Follow-up data was analyzed using Cox regression according to time-varying exposure to meaningful decreases (>5 %) in VWF (‘VWF-responders’) vs. stable/increasing VWF levels (<5 % decrease, ‘VWF-non-responders’) upon NSBB treatment.

Results 159 patients with a median Child-Pugh score of 8(IQR:6;9) were included. Upon NSBB treatment, VWF-response was observed in 97(61.0 %) patients (median relative decrease:-14.7[IQR:-21.4;-10.0]%), while 77 (48.4 %) patients were HVPG responders.The rates of HVPG-response were comparable between VWF-response groups (VWF-responders:49.5 % vs. VWF-non-responders:56.8 %;p = 0.864). However, VWF-responders showed more pronounced relative reductions in SI, i.e. procalcitonin (-20.2[IQR:-34.1;-3.8]% vs. VWF-non-responders:20.0[IQR:11.7;36.4]%;p = 0.001) and CRP (-26.2[IQR:-50.1;11.8]% vs. VWF-non-responders:-3.5[IQR:-33.1;10.0]%;p = 0.050). Conversely, NSBB-induced relative decreases in MAP were less pronounced in VWF-responders (-8.0[IQR:-15.0;0]%) than in VWF-non-responders (-12.2[IQR:-18.5;-2.8]%;p = 0.044).In adjusted Cox regression models, 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), acute-on-chronic liver failure (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).

Conclusion NSBB-related reductions in VWF levels might reflect their anti-inflammatory activity. Decreases in VWF are paralleled by less pronounced adverse effects on systemic hemodynamics and decreased risks of further decompensation, ACLF and death.

Publication History

Article published online:
01 September 2021