Reply.

Abstract

Potential conflict of interest: Nothing to report. We thank Pang et al. for their interest in our study. In our recent publication, we observed that von Willebrand factor antigen (vWF‐Ag) seems to be critically involved in liver regeneration after liver resection in humans. Indeed, we agree that vWF‐Ag might be involved in mechanisms with potentially opposing effects. In fact, this is nicely demonstrated within our present study: while patients with high preoperative levels of vWF‐Ag were found to have an increased risk for postoperative complications, an increase in vWF‐Ag during the very early phase of liver regeneration seemed to be required to allow for adequate postoperative liver regeneration. In this context, preoperative levels of vWF‐Ag presumably reflect the degree of parenchymal damage and portal hypertension. In contrast, the initial vWF‐Ag burst during early liver regeneration seems to be central for induction and success of platelet‐mediated liver regeneration, which is in line with experimental data.1 Similar to its involvement in liver disease and regeneration, there is evidence for both a protumorigenic and an antitumorigenic property of vWF‐Ag.2 While Pang and coworkers specifically referred to hepatocellular carcinoma, current literature describes vWF‐Ag as a modulator in a variety of malignant neoplasms.3 Still, the underlying pathophysiologic mechanisms seem to be similar for nearly all investigated entities. In summary, studies show an antiangiogenic role of vWF‐Ag supposedly as a consequence of negative interaction with receptors for vascular endothelial growth factor. Further, a direct proapoptotic effect of vWF‐Ag could be shown. Most puzzling, however, is the function of vWF‐Ag in tumor metastasis: while a prometastatic role of vWF‐Ag, most likely through augmentation of tumor cell binding on platelets and endothelial cells, was independently shown by several studies, experimental data revealed an increased metastatic potential for transplanted tumor cells in vWF‐deficient mice. Based on the available data, one has to acknowledge the probability of opposing functions of vWF‐Ag. As we recently reported on the bivalent role of a key molecule of liver regeneration,4 a similar involvement of vWF‐Ag in patients undergoing liver surgery is indeed conceivable. Still, there is a lack of human data in regard to functional properties of vWF‐Ag in tissue regeneration and cancer. Thus, we fully agree with Pang et al. and encourage further work on the pathophysiologic involvement of vWF‐Ag in this area. Author names in bold designate shared co‐first authorship.