Abstract：
BACKGROUND: Posthepatectomy liver failure (PHLF), complications of portal hypertension, and disease recurrence determine the outcome for hepatocellular carcinoma (HCC) patients undergoing liver resection. This study aimed to evaluate the von Willebrand factor antigen (vWF-Ag) as a non-invasive test for clinically significant portal hypertension (CSPH) and a predictive biomarker for time to recurrence (TTR) and overall survival (OS).
METHODS: The study recruited 72 HCC patients with detailed preoperative workup from a prospective trial (NCT02118545) and followed for complications, TTR, and OS. Additionally, 163 compensated patients with resectable HCC were recruited to evaluate vWF-Ag cutoffs for ruling out or ruling in CSPH. Finally, vWF-Ag cutoffs were prospectively evaluated in an external validation cohort of 34 HCC patients undergoing liver resection.
RESULTS: In receiver operating characteristic (ROC) analyses, vWF-Ag (area under the curve [AUC], 0.828) was similarly predictive of PHLF as indocyanine green clearance (disappearance rate: AUC, 0.880; retention rate: AUC, 0.894), whereas computation of future liver remnant was inferior (AUC, 0.756). Cox-regression showed an association of vWF-Ag with TTR (per 10%: hazard ratio [HR], 1.056; 95% confidence interval [CI] 1.017-1.097) and OS (per 10%: HR, 1.067; 95% CI 1.022-1.113). In the analyses, VWF-Ag yielded an AUC of 0.824 for diagnosing CSPH, with a vWF-Ag of 182% or lower ruling out and higher than 291% ruling in CSPH. Therefore, a highest-risk group (> 291%, 9.7% of patients) with a 57.1% incidence of PHLF was identified, whereas no patient with a vWF-Ag of 182% or lower (52.7%) experienced PHLF. The predictive value of vWF-Ag for PHLF and OS was externally validated.
CONCLUSIONS: For patients with resectable HCC, VWF-Ag allows for simplified preoperative risk stratification. Patients with vWF-Ag levels higher than 291% might be considered for alternative treatments, whereas vWF-Ag levels of 182% or lower identify patients best suited for surgery.
METHODS: The study recruited 72 HCC patients with detailed preoperative workup from a prospective trial (NCT02118545) and followed for complications, TTR, and OS. Additionally, 163 compensated patients with resectable HCC were recruited to evaluate vWF-Ag cutoffs for ruling out or ruling in CSPH. Finally, vWF-Ag cutoffs were prospectively evaluated in an external validation cohort of 34 HCC patients undergoing liver resection.
RESULTS: In receiver operating characteristic (ROC) analyses, vWF-Ag (area under the curve [AUC], 0.828) was similarly predictive of PHLF as indocyanine green clearance (disappearance rate: AUC, 0.880; retention rate: AUC, 0.894), whereas computation of future liver remnant was inferior (AUC, 0.756). Cox-regression showed an association of vWF-Ag with TTR (per 10%: hazard ratio [HR], 1.056; 95% confidence interval [CI] 1.017-1.097) and OS (per 10%: HR, 1.067; 95% CI 1.022-1.113). In the analyses, VWF-Ag yielded an AUC of 0.824 for diagnosing CSPH, with a vWF-Ag of 182% or lower ruling out and higher than 291% ruling in CSPH. Therefore, a highest-risk group (> 291%, 9.7% of patients) with a 57.1% incidence of PHLF was identified, whereas no patient with a vWF-Ag of 182% or lower (52.7%) experienced PHLF. The predictive value of vWF-Ag for PHLF and OS was externally validated.
CONCLUSIONS: For patients with resectable HCC, VWF-Ag allows for simplified preoperative risk stratification. Patients with vWF-Ag levels higher than 291% might be considered for alternative treatments, whereas vWF-Ag levels of 182% or lower identify patients best suited for surgery.
摘要：
背景：切除术后肝功能衰竭（PHLF），门静脉高压症的并发症，和疾病复发决定了肝细胞癌（HCC）患者接受肝切除术的结局。这项研究旨在评估vonWillebrand因子抗原（vWF-Ag）作为临床上显着的门脉高压（CSPH）的非侵入性测试，以及复发时间（TTR）和总生存期（OS）的预测性生物标志物。
方法：该研究从一项前瞻性试验（NCT02118545）招募了72例肝癌患者，并随访并发症，TTR,和OS。此外,163例代偿的可切除HCC患者被招募来评估vWF-Ag截止值，以排除或裁定CSPH。最后,在34例接受肝切除术的HCC患者的外部验证队列中，对vWF-Ag截止值进行了前瞻性评估。
结果：在接收器工作特性(ROC)分析中，vWF-Ag(曲线下面积[AUC]，0.828)与吲哚菁绿清除率(消失率：AUC，0.880；保留率：AUC，0.894),而未来肝脏残留的计算较差(AUC，0.756).Cox回归显示vWF-Ag与TTR（每10%：危险比[HR]，1.056；95%置信区间[CI]1.017-1.097)和OS(每10%：HR，1.067；95%CI1.022-1.113）。在分析中，VWF-Ag诊断CSPH的AUC为0.824，vWF-Ag为182%或更低的排除，高于291%的CSPH裁决。因此,最高风险组(>291%，9.7%的患者)发现了57.1%的PHLF发生率，而vWF-Ag为182％或更低（52.7％）的患者没有经历PHLF。vWF-Ag对PHLF和OS的预测价值进行了外部验证。
结论：对于可切除的HCC患者，VWF-Ag允许简化术前风险分层。vWF-Ag水平高于291％的患者可能会考虑进行替代疗法，而182%或更低的vWF-Ag水平确定患者最适合手术。
方法：该研究从一项前瞻性试验（NCT02118545）招募了72例肝癌患者，并随访并发症，TTR,和OS。此外,163例代偿的可切除HCC患者被招募来评估vWF-Ag截止值，以排除或裁定CSPH。最后,在34例接受肝切除术的HCC患者的外部验证队列中，对vWF-Ag截止值进行了前瞻性评估。
结果：在接收器工作特性(ROC)分析中，vWF-Ag(曲线下面积[AUC]，0.828)与吲哚菁绿清除率(消失率：AUC，0.880；保留率：AUC，0.894),而未来肝脏残留的计算较差(AUC，0.756).Cox回归显示vWF-Ag与TTR（每10%：危险比[HR]，1.056；95%置信区间[CI]1.017-1.097)和OS(每10%：HR，1.067；95%CI1.022-1.113）。在分析中，VWF-Ag诊断CSPH的AUC为0.824，vWF-Ag为182%或更低的排除，高于291%的CSPH裁决。因此,最高风险组(>291%，9.7%的患者)发现了57.1%的PHLF发生率，而vWF-Ag为182％或更低（52.7％）的患者没有经历PHLF。vWF-Ag对PHLF和OS的预测价值进行了外部验证。
结论：对于可切除的HCC患者，VWF-Ag允许简化术前风险分层。vWF-Ag水平高于291％的患者可能会考虑进行替代疗法，而182%或更低的vWF-Ag水平确定患者最适合手术。
