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

Patrick Starlinger, Joseph C. Ahn, Aidan Mullan, Georg P. Gyoeri, David Pereyra, Roberto Alva-Ruiz, Hubert Hackl, Thomas Reiberger, Michael Trauner, Jonas Santol, Benedikt Simbrunner, Mattias Mandorfer, Gabriela Berlakovich, Patrick S. Kamath, Julie Heimbach

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Aims: Patients with cirrhosis on the liver transplant (LT) waiting list may die or be removed because of 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. Approach and Results: We determined whether addition of vWF-Ag and CRP to the Model for End-Stage Liver Disease-Sodium (MELD-Na) score improves risk stratification of patients awaiting LT. CRP and vWF-Ag at LT listing were assessed in two 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, whereas CRP closely, and MELD independently, correlated with biomarkers of bacterial translocation/inflammation. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1533-1545
Number of pages13
JournalHepatology
Volume74
Issue number3
DOIs
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Hepatology

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