The von Willebrand Factor Facilitates Model for End‐Stage Liver Disease–Independent Risk Stratification on the Waiting List for Liver Transplantation

Abstract

Background and Aims The Model for End‐Stage Liver Disease (MELD) is used for clinical decision‐making and organ allocation for orthotopic liver transplantation (OLT) and was previously upgraded through inclusion of serum sodium (Na) concentrations (MELD‐Na). However, MELD‐Na may underestimate complications arising from portal hypertension or infection. The von Willebrand factor (vWF) antigen (vWF‐Ag) correlates with portal pressure and seems capable of predicting complications in patients with cirrhosis. Accordingly, this study aimed to evaluate vWF‐Ag as an adjunct surrogate marker for risk stratification on the waiting list for OLT. Approach and Results Hence, WF‐Ag at time of listing was assessed in patients listed for OLT. Clinical characteristics, MELD‐Na, and mortality on the waiting list were recorded. Prediction of 3‐month waiting‐list survival was assessed by receiver operating characteristics and net reclassification improvement. Interestingly, patients dying within 3 months on the waiting list displayed elevated levels of vWF‐Ag (P < 0.001). MELD‐Na and vWF‐Ag were comparable and independent in their predictive potential for 3‐month mortality on the waiting list (area under the curve [AUC], vWF‐Ag = 0.739; MELD‐Na = 0.764). Importantly, a vWF‐Ag cutoff at 413% identified patients at risk for death within 3 months of listing with a higher odds ratio (OR) than the previously published cutoff at a MELD‐Na of 20 points (vWF‐Ag, OR = 10.873, 95% confidence interval [CI], 3.160, 36.084; MELD‐Na, OR = 7.594, 95% CI, 2.578, 22.372; P < 0.001, respectively). Ultimately, inclusion of vWF‐Ag into the MELD‐Na equation significantly improved prediction of 3‐month waiting‐list mortality (AUC, MELD‐Na–vWF = 0.804). Conclusions A single measurement of vWF‐Ag at listing for OLT predicts early mortality. Combining vWF‐Ag levels with MELD‐Na improves risk stratification and may help to prioritize organ allocation to decrease waiting‐list mortality.

The Addition of C‐Reactive Protein and von Willebrand Factor to Model for End‐Stage Liver Disease‐Sodium Improves Prediction of Waitlist Mortality

“…In particular, the identification of high-risk patients with low MELD-Na score at listing, as well as further stratification of patients with a very high MELD-Na score pose difficult challenges (7-10). We previously documented that vWF-Ag significantly improved prediction of 3month waitlist mortality (13). However, a previous report from our group that was based on a different patient population indicated that the combination of CRP and vWF-Ag is particularly powerful to predict outcome in end-stage liver disease patients (12).…”

“…For the exploration cohort, all patients listed for LT between 2003 and 2016 at the Medical University of Vienna were included in this study. This particular set of patients was recently assessed for the relevance of vWF-Ag in 3-month waitlist mortality prediction and was now further evaluated (13). Routine blood samples at time of listing included baseline coagulation parameters, liver and kidney function tests as well as CRP and vWF-Ag levels.…”

“…All rights reserved for 3-month waitlist mortality, vWF-Ag did also exhibit the potential to identify patients who actually had a lower risk for 3-month waitlist mortality than expected based on MELD-Na. vWF-Ag has been shown to be a highly versatile biomarker in patients with underlying chronic liver disease, as it provides clinically meaningful information in several different clinical contexts/stages of liver disease (11)(12)(13)(30)(31)(32)(33)(34)(35)(36)(37). VWF-Ag is stored in endothelial cells' Weibel-Palade-bodies and alpha-granules of platelets.…”

“…Patients with cirrhosis and portal hypertension have an elevated level of von Willebrand factor antigen (vWF-Ag) (11,12). In this context, we recently demonstrated that the addition of von Willebrand factor antigen (vWF-Ag), a key indicator of endothelial cell dysfunction and associated portal hypertension (11), significantly improved the predictive performance of MELD-Na for 3-month waitlist mortality (13). Besides vWF-Ag, accumulating evidence suggest that an elevated CRP may also exhibit a predictive potential in patients with end stage liver disease (14)(15)(16).…”

Noninvasive Diagnostics for Portal Hypertension: A Comprehensive Review

“…Finally, VWF antigen levels have recently been shown to predict hepatic decompensation in patients with compensated cirrhosis (including patients with HCV-induced cirrhosis who had achieved sustained virologic response [SVR]) 94 and further improve model for end-stage liver disease (MELD)-Na-based risk stratification in patients listed for liver transplantation. 95 In addition, it may also predict liver failure following hepatectomy. 96 In summary, there is a plethora of simple blood-based biomarkers of portal hypertension; however, except for PLT (if combined with other parameters), none of the indirect markers of liver fibrosis markers is suitable for diagnosing CSPH in clinical practice.…”