Von Willebrand factor antigen as a versatile preoperative marker in patients undergoing liver resection for hepatocellular carcinoma

Abstract

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: Risk evaluation in patients with hepatocellular carcinoma (HCC) prior to liver resection is an ongoing debate in the field, as long-term outcome is affected by an increased risk for LD and early disease recurrence. Currently available predictors are costly, not broadly available and lack predictive accuracy. Recently, vWF-Ag was established as a marker for postoperative LD. Due to its pleiotropic associations with components of HCC pathology vWF-Ag was further investigated in a variety of malignant diseases. This study aimed to compare routinely available parameters of risk assessment in HCC patients prior to liver resection and investigate the role of von Willebrand factor antigen (vWF-Ag) as a biomarker for postoperative liver dysfunction (LD), disease recurrence and long-term overall survival (OS). Methods: A total of 72 patients suffering from HCC was included out of a prospective trial cohort investigating the predictive potential of vWF-Ag for immediate outcome after liver resection in 223 patients (ClinicalTrials.gov-Identifier:NCT02118545). Patients clinical course was documented and they were followed up for disease recurrence and OS after discharge. Results: Upon logistic regression only vWF-Ag, volumentric assessment of future liver remnant (FLR) and measures of indocyanine green clearance (ICG-C) were able to predict patients risk for development of LD. In direct comparison using ROC-analysis, vWF-Ag was found to be comparable to parameters of ICG-C (area under the curve [AUC] = 0.828, vs 0.894 and 0.880) and more accurate than FLR (AUC = 0.756) and hepatic venous pressure gradient (HVPG, AUC = 0.590). Multivariable Cox-regression further revealed an independent association of vWF-Ag with disease free survival (odds ratio [OR] = 1.004, 95% confidence interval [CI] : 1.000-1.008). Ultimately, prediction of OS according to preoperative vWF-Ag was independent from development of postoperative LD, morbidity and disease recurrence. Given the clinical relevance to identify patients that might not benefit from liver resection and better served with other treatment options we defined a high risk cohort that developed LD in 55.6% of the cases (vs. 12.7% in vWF-AgLOW patients, p = 0.002) and had a 50% risk for postoperative mortality within the first postoperative year (vs. 11.7% in vWF-AgLOW patients, p = 0.006). Conclusion: Preopertive vWF-Ag is comparable to or more accurate than costly methods of preoperative risk evaluation, including volumetric estimation of FLR, ICG-C and HVPG measurement. In addition, preoperative vWF-Ag is associated with OS independent of postoperative outcome. The present data stresses the use of vWF-Ag as a broadly available routine laboratory parameter in preoperative risk evaluation for HCC patients and suggests that it might allow to personalize surgical strategy and treatment plan to the individual patient.