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

Hepatology. 2012 Oct;56(4):1439-47. doi: 10.1002/hep.25806. Epub 2012 Aug 27.

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 = 0.69; P < 0.0001) and predicted CSPH independently of Child Pugh score. Higher vWF-Ag levels were associated with varices (odds ratio [OR] = 3.27; P < 0.001), ascites (OR = 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 = 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] = 0.71 for vWF-Ag versus AUC = 0.65 for MELD; P = 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cohort Studies
  • Confidence Intervals
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension, Portal / blood*
  • Hypertension, Portal / mortality*
  • Hypertension, Portal / physiopathology
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / mortality*
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / physiopathology
  • Liver Failure / blood*
  • Liver Failure / mortality
  • Liver Failure / pathology
  • Liver Failure / physiopathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Predictive Value of Tests
  • Proportional Hazards Models
  • ROC Curve
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Survival Analysis
  • Time Factors
  • von Willebrand Factor / metabolism*

Substances

  • Biomarkers
  • von Willebrand Factor