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维生素K缺乏诱导的凝血酶原II作为肝细胞癌活体肝移植预后因素的研究

Prothrombin-induced by vitamin K absence II as a prognostic factor in living donor liver transplantation for hepatocellular carcinoma.

作者信息

Bhatti Abu Bakar Hafeez, Shafique Usman, Ahmed Nazish, Abbas Ghazanfar, Atiq Muslim, Zia Haseeb Haider, Khan Nusrat Yar, Rana Atif

机构信息

Department of HPB Surgery and Liver Transplantation , Shifa International Hospital Islamabad , Islamabad, Pakistan.

Department of Surgery , Shifa Tameer-e-Millat University Islamabad , Islamabad , Pakistan.

出版信息

Sci Rep. 2025 Jul 1;15(1):21900. doi: 10.1038/s41598-025-08103-1.

Abstract

In hepatocellular carcinoma (HCC), there is a need for novel tumor markers to enhance patient selection for liver transplantation. This study evaluates the prognostic value of Prothrombin Induced by Vitamin K Absence-II (PIVKA-II) in predicting microvascular invasion (MVI) and post-transplant recurrence, either alone or in combination with alpha-fetoprotein (AFP), following living donor liver transplantation (LDLT). We reviewed 400 patients who underwent LDLT under expanded criteria (largest tumor diameter ≤ 10 cm, any tumor number, AFP < 1000 ng/ml). PIVKAII outperformed AFP and tumor size in predicting MVI, with a C-statistic of 0.777 compared to 0.579 and 0.631. On multivariate analysis, AFP > 20 ng/ml [HR 3.3, P = 0.003] and PIVKAII > 1000 mAU/ml [HR 3.5, P = 0.001] were predictors of recurrence. PIVKAII > 1000 mAU/ml was associated with MVI (21.6% vs. 65.7%, P < 0.001) and lower 5-year RFS (79% vs. 50%, P < 0.001). A combination of AFP > 20 ng/ml and PIVKAII > 1000 mAU/ml predicted 47.1% of recurrences, whereas HCC recurred in 6.1% of patients not meeting this threshold. The 5-year RFS was 45% for dual tumor marker positive HCC versus 77% for all others (P < 0.001). PIVKAII is a strong predictor of MVI and post-transplant recurrence. Dual tumor marker-positive HCC can serve as an exclusion criterion for upfront LDLT.

摘要

在肝细胞癌(HCC)中,需要新的肿瘤标志物来优化肝移植患者的选择。本研究评估了维生素K缺乏诱导蛋白-II(PIVKA-II)在预测活体肝移植(LDLT)后微血管侵犯(MVI)和移植后复发方面的预后价值,单独使用或与甲胎蛋白(AFP)联合使用。我们回顾了400例在扩大标准下接受LDLT的患者(最大肿瘤直径≤10 cm,任何肿瘤数量,AFP<1000 ng/ml)。在预测MVI方面,PIVKAII优于AFP和肿瘤大小,C统计量为0.777,而AFP和肿瘤大小分别为0.579和0.631。多因素分析显示,AFP>20 ng/ml [HR 3.3,P=0.003]和PIVKAII>1000 mAU/ml [HR 3.5,P=0.001]是复发的预测因素。PIVKAII>1000 mAU/ml与MVI相关(21.6%对65.7%,P<0.001),5年无复发生存率较低(79%对50%,P<0.001)。AFP>20 ng/ml和PIVKAII>1000 mAU/ml联合预测47.1%的复发,而未达到该阈值的患者中HCC复发率为6.1%。双肿瘤标志物阳性的HCC患者5年无复发生存率为45%,而其他患者为77%(P<0.001)。PIVKAII是MVI和移植后复发的有力预测指标。双肿瘤标志物阳性的HCC可作为直接LDLT的排除标准。

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