Von Willebrand factor as new noninvasive predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis

Abstract

von Willebrand factor antigen (vWF-Ag) is elevated in patients with liver cirrhosis, but the clinical significance is unclear. We hypothesized that vWF-Ag levels may correlate with portal pressure, measured by hepatic venous pressure gradient (HVPG), and predict clinically significant portal hypertension (CSPH; HVPG !10 mmHg), decompensation and mortality. Portal hemodynamics were assessed by HVPG measurement, whereas vWF-Ag levels were measured by enzyme-linked immunosorbent assay. During follow-up, complications of liver cirrhosis, death or transplantation were recorded. Two hundred and eighty-six patients (205 male and 81 female; mean age, 56 years) with liver cirrhosis were included. vWF-Ag correlated with HVPG (r 5 0.69; P < 0.0001) and predicted CSPH independently of Child Pugh score. Higher vWF-Ag levels were associated with varices (odds ratio [OR] 5 3.27; P < 0.001), ascites (OR 5 3.93; P < 0.001) and mortality (hazard ratio: 4.41; P < 0.001). Using a vWF-Ag cut-off value of !241%, the AUC for detection of CSPH in compensated patients was 0.85, with a positive predictive value and negative predictive value of 87% and 80%, respectively. Compensated patients had 25% mortality after 53 months if the vWF-Ag was <315% compared to 15 months in patients with vWF-Ag >315% (P < 0.001). Decompensated patients had a mortality of 25% after 37 and 7 months if their vWF-Ag was <315% and >315%, respectively (P 5 0.002). In compensated patients with a vWF-Ag >315% median time to decompensation or death was 32 months compared with 59 months in patients with vWF-Ag <315%. vWF-Ag equals Model for End-Stage Liver Disease (MELD) in mortality prediction (area under the curve [AUC] 5 0.71 for vWF-Ag versus AUC 5 0.65 for MELD; P 5 0.2). Conclusion: vWF-Ag is a new, simple and noninvasive predictor of CSPH. A vWF-Ag cut-off value at 315% can clearly stratify patients with compensated and decompensated liver cirrhosis in two groups with completely different survival. vWF-Ag may become a valuable marker for the prediction of mortality in patients with liver cirrhosis in clinical practice.

Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference

“…In cirrhosis, endothelial dysfunction has been surmised by the observation of changes in levels of nitric oxide-derived by-products [61,62], flow mediated vasodilatory response of the brachial artery [63] and VWF levels [64][65][66][67][68]. Currently, there is no single marker that can detect endothelial dysfunction in patients with cirrhosis.…”

Model for End-stage Liver Disease

“…In one study, comparing these models, UKELD and updated MELD were poor in predicting mortality compared to other 4 models. 132 Other factors shown to improve the MELD accuracy are HVPG, 133 von Willebrand factor level at a cut-off level of 315%, 134 persistent CRP levels of $29 mg/L, 135 prealbumin levels of >69 mg/L, 136 apoptosis marker CK-18. 137 Refinements to improve the accuracy of MELD would continue and until we find a better score, livers could continue to be allocated using the current MELD based system.…”

Predictors of Bleeding from Esophageal Varices: The Role of Factor VII and von Willebrand Factor (vWF)

“…VWF-Ag plays an important role in primary haemostasis and development of thrombotic vascular obliteration is discussed as a possible mechanism leading to portal hypertension [19]. Endothelial dysfunction is a major determinant of the increased hepatic vascular tone of cirrhotic livers.…”