Bhatti Abu Bakar Hafeez, Shafique Usman, Ahmed Nazish, Abbas Ghazanfar, Atiq Muslim, Zia Haseeb Haider, Khan Nusrat Yar, Rana Atif
Department of HPB Surgery and Liver Transplantation , Shifa International Hospital Islamabad , Islamabad, Pakistan.
Department of Surgery , Shifa Tameer-e-Millat University Islamabad , Islamabad , Pakistan.
Sci Rep. 2025 Jul 1;15(1):21900. doi: 10.1038/s41598-025-08103-1.
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.
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。
