The Addition of C-Reactive Protein and von Willebrand Factor to MELD-Na Improves Prediction of Waitlist Mortality.

Patients with cirrhosis on the liver transplant (LT) waiting list may die or be removed due to complications of portal hypertension (PH) or infections. Von Willebrand factor antigen (vWF-Ag) and C-reactive protein (CRP) are simple, broadly available markers of these processes. We determined whether addition of vWF-Ag and CRP to the MELD-Na score improves risk stratification of patients awaiting LT. CRP and vWF-Ag at LT listing were assessed in 2 independent cohorts (Medical University of Vienna [exploration cohort] and Mayo Clinic Rochester [validation cohort]). Clinical characteristics, MELD-Na and mortality on the waiting list were recorded. Prediction of 3-month waiting list mortality was assessed by receiver operating characteristics curve (ROC-AUC). In order to explore potential mechanisms underlying the prognostic utility of vWF-Ag and CRP in this setting, we evaluated their association with PH, bacterial translocation, systemic inflammation, and circulatory dysfunction. In the exploration cohort (N=269) vWF-Ag and CRP both improved the predictive value of MELD-Na for 3-month waitlist mortality and showed the highest predictive value when combined (AUC: MELD-Na: 0.764, MELD-Na+CRP: 0.790, MELD-Na+vWF: 0.803, MELD-Na+CRP+vWF-Ag: 0.824). Results were confirmed in an independent validation cohort (N=129, AUC: MELD-Na: 0.677, MELD-Na+CRP+vWF-Ag: 0.882). vWF-Ag was independently associated with PH and inflammatory biomarkers, while CRP closely, and MELD-independently, correlated with biomarkers of bacterial translocation/inflammation. CONCLUSION: The addition of vWF-Ag and CRP - reflecting central pathophysiological mechanisms of PH, bacterial translocation and inflammation, that are all drivers of mortality on the waiting list for LT - to the MELD-Na score improves prediction of waitlist mortality. Using the vWFAg-CRP-MELD-Na model for prioritizing organ allocation may improve prediction of waitlist mortality and decrease waitlist mortality.