title: 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 = 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Ferlitsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiberger
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoke
authors.forename: Petra
authors.initials: P
authors.lastname: Salzl
authors.forename: Bernadette
authors.initials: B
authors.lastname: Schwengerer
authors.forename: Gregor
authors.initials: G
authors.lastname: Ulbrich
authors.forename: Berit Anna
authors.initials: BA
authors.lastname: Payer
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.forename: Arnulf
authors.initials: A
authors.lastname: Ferlitsch
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D016001:Confidence Intervals; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology; D017093:Liver Failure / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014841:von Willebrand Factor