Von Willebrand factor for outcome prediction within different clinical stages of advanced chronic liver disease

Background Although von Willebrand factor (VWF)-levels have been reported to predict hepatic decompensation/mortality, the specific prognostic value of VWF in distinct clinical stages (CS) has not been systematically assessed.

Aims&Methods Therefore, we compared changes in prognostic biomarkers throughout the clinical spectrum of ACLD and established CS-specific VWF cut-offs for risk-prediction. Patients undergoing HVPG-measurement at the Vienna Hepatic Hemodynamic Lab with evidence of ACLD were considered. CS were defined as follows: Probable compensated ACLD (cACLD):LSM≥10kPa&HVPG<6mmHg/0:cACLD&6-9mmHg/1:cACLD&HVPG≥10mmHg/2:decompensated ACLD (dACLD) with bleeding/3:dACLD with non-bleeding decompensation/4:≥2 decompensations.

Results 923 patients were included. We observed a steady step-wise increase of VWF with CS-progression. In contrast, HVPG levelled off in dACLD with only modest numerical differences between CS2-4, whereas MELD showed only minor changes in early CS and CRP did not increase until CS3, i.e., non-bleeding decompensation.

cACLD patients with VWF-levels above the stage-specific 75^th-percentile (≥342 %) had a more than four-times increased risk of decompensation/death (HR:4.17[95 %CI:2.20-7.90];p<0.001). In dACLD patients, VWF-levels above the 75^th-percentile (≥418 %) were associated with a 67 %-increased risk (HR:1.67[95 %CI:1.28-2.19];p<0.001), while having values below the 25^th-percentile (<268 %) nearly halved the risk (HR:0.57[95 %CI:0.42-0.78];p<0.001) of decompensation/death.

Importantly, even in a fully adjusted model (age, etiology, HVPG, MELD, albumin, and CRP), VWF was independently associated with hepatic decompensation/death in cACLD. In dACLD, VWF remained independently predictive after adjusting for MELD, but not when adjusting for additional variables.

Discussion Among the investigated parameters, VWF was the only prognostic indicator that steadily increased throughout all CS of ACLD. Its prognostic implications are particularly pronounced in cACLD patients, in whom VWF ≥342 % identify those who are at a four-fold increased risk of hepatic decompensation/death. In dACLD, VWF cut-offs <268 % and ≥418 % identify low- and high-risk populations. The proposed stage-dependent VWF cut-offs are easily applicable in clinical routine and may help to broaden the use of VWF for risk stratification and treatment individualization.

Publication History

Article published online:
01 September 2021