In transplantation medicine, the top priority is to ensure appropriate allocation of donor organs to patients with the most urgent need. In a recent study, by integrating a single laboratory parameter—the von Willebrand factor antigen (VWF)—researchers from Medical University of Vienna’s department of surgery have managed to significantly increase the accuracy of predicting the probability of dying while on the waiting list for a liver transplant, thereby taking a huge step toward improving organ allocation.1

Patrick Starlinger, MD, PhD, Medical University of Vienna.

Patrick Starlinger, MD, PhD, Medical University of Vienna.

Like other countries that participate in the Eurotransplant organization, Austria allocates organs to patients on the liver transplant waiting list on the basis of medical urgency. Currently, patients are listed using the model for end-stage liver disease (MELD), which results in a score made up of three laboratory parameters. However, the MELD score has obvious limitations, and the rate of mortality for patients on the waiting list continues to be approximately 20%.

What is particularly challenging in this context is identifying patients at high risk of life-threatening bleeds due to portal hypertension or infections, even though they have a low MELD score.

“We have been looking for a simple way of overcoming the existing weaknesses of MELD-based allocation and of identifying patients with a high risk, despite having a low MELD score,” says transplant surgeon Georg Györi, MD, head of the transplantation outpatient clinic at Vienna General Hospital and one of the two lead authors of the study.

VWF antigen is a protein stored in thrombocytes and endothelial cells that plays and a key role in hemostasis (blood clotting). In previous studies, VWF antigen was found to be an excellent marker for endothelial cell dysfunction, and was recently also identified as being a central factor in postoperative liver regeneration.

A clear correlation was also recently observed between VWF antigen and portal hypertension and its complications. “This is particularly important, since this is one of the main causes of patients dying while on the waiting list for a liver transplant,” says David Pereyra, MD, PhD, also a lead author of the study. “The great advantage is that VWF antigen can easily be determined during routine blood sampling carried out when patients are being listed.”

The study has now shown that VWF antigen can actually predict waiting-list mortality independently of the established MELD score. The authors also showed that VWF antigen can significantly improve accuracy in combination with the MELD score.

“We were surprised at the huge impact of adding VWF antigen determination to the MELD score,” says principal investigator Patrick Starlinger, MD, PhD, consultant surgeon in the department of surgery and head of the research group for translational and experimental liver research at the Medical University of Vienna. “Indeed, the VWF antigen appears to reflect an entirely new aspect of mortality on the waiting list, thus greatly improving risk stratification. By measuring this single parameter, it is possible to improve the prediction of 3-month-survival on the waiting list by as much as 12.5%.”

“These groundbreaking results arose out of the excellent interdisciplinary collaboration between gastroenterology and surgery and have the potential to change the basis for organ allocation throughout the world,” says Gabriela Berlakovich, MD, head of transplant surgery at Vienna General Hospital.

Reference

1. Györi GP, Pereyra D, Rumpf B, et al. Von Willebrand factor facilitates MELD-independent risk stratification on the waiting list for liver transplantation. Hepatology. Epub before print, November 27, 2019; doi: 10.1002/hep.31047.

Featured image: © Anton Skavronskiy, courtesy Dreamstime (ID 127617799).