Bivalent property of intra-platelet VWF in liver regeneration and HCC recurrence: A prospective multicenter study

Article type: Research Article

Authors: Aryal, Bibek^{a; *} | Yamakuchi, Munekazu^{b; *} | Shimizu, Toshiaki^b | Kadono, Jun^c | Furoi, Akira^c | Gejima, Kentaro^a | Takenouchi, Kazunori^b | Komokata, Teruo^d | Hashiguchi, Teruto^{b; *} | Imoto, Yutaka^a

Affiliations: [a] Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan | [b] Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan | [c] Department of Surgery, Kirishima Medical Center, Kirishima 899-5112, Japan | [d] Department of Surgery, Kagoshima Medical Center, National Hospital Organization, Kagoshima 892-0853, Japan

Correspondence: [*] Corresponding authors: Bibek Aryal, drbibekaryal@gmail.com; Teruto Hashiguchi, terutoha@m3.kufm.kagoshima-u.ac.jp; Mune-kazu Yamakuchi, munekazu@m.kufm.kagoshima-u.ac.jp.

Abstract: BACKGROUND AND AIMS: A striking difference has been observed in structure and functional properties between plasma and platelet von Willebrand factor (VWF). While the existing evidence has revealed a clinical relevance of plasma VWF-Ag in liver regeneration (LR) and different cancers, this study was designed to explore the properties of intra-platelet (IP) and serum VWF-Ag in patients with hepatocellular carcinoma (HCC) undergoing partial hepatectomy. METHODS: A total of 40 patients undergoing partial hepatectomy were prospectively recruited from 3 institutions. VWF-Ag concentrations were evaluated mainly in serum and platelet extracts. Patients were followed-up for postoperative liver dysfunction and HCC recurrence. RESULTS: We observed a post-resection increase in the concentration of VWF-Ag in serum and platelet. Patients with postoperative liver dysfunction had substantially reduced serum and IP VWF-Ag concentrations. After a 2-year follow-up, patients with higher post-resection serum and IP VWF-Ag concentrations were found to develop early HCC recurrence. Likewise, IP VWF-Ag was able to independently predict post-resection early HCC recurrence. CONCLUSION: This multicenter, prospective, pilot study demonstrates a bivalent property of IP VWF in LR and oncological outcome; low preoperative VWF appeared to have a negative association on post-resection liver dysfunction, whereas, patients with higher post-resection VWF-Ag concentrations were found to have early HCC recurrence.

Keywords: Platelet, von Willebrand Factor, liver regeneration, HCC, HCC recurrence

DOI: 10.3233/CBM-190168

Journal: Cancer Biomarkers, vol. 26, no. 1, pp. 51-61, 2019