Introduction: AFP and the RETREAT score are currently used to predict HCC recurrence after LT. However, superior discriminating models are needed for low AFP populations. The aim of this study is to investigate the predictive value of PIVKA-II on recurrence-free survival after LT in a low AFP population and microvascular invasion on explant. Methods: A retrospective cohort study including all consecutive patients transplanted for HCC between 1989 and 2019 in the Erasmus MC University Medical Center in Rotterdam, the Netherlands, was used. AFP and PIVKA-II levels were determined in serum samples collected at the time of transplantation. Data on tumor load and microvascular invasion were retrieved from patients’ records. Results: The study cohort consisted of 121 patients, with HCC recurrence in 15 patients (12.4%). The median AFP was 7.7 ng/mL (4.4–20.2), and the median PIVKA-II was 72.0 mAU/mL (41.0–213.5). Patients with low AFP (≤8 ng/mL) and PIVKA-II (≤90 mAU/mL) had a 5-year recurrence-free survival of 100% compared to 85.7% in patients with low AFP and high PIVKA-II (p= 0.026). Regardless of the AFP level, patients within the Milan criteria (based on explant pathology) with a low PIVKA-II level had a 5-year recurrence-free survival of 100% compared to patients with a high PIVKA-II level of 81.1% (p= 0.002). In patients with microvascular invasion, the AUC for PIVKA-II was slightly better than the AUC for AFP (0.775 vs. 0.687). Conclusions: The dual model of PIVKA-II ≤ 90 mAU/mL with either AFP ≤ 8 ng/mL or with patients within the Milan criteria identifies patient groups which can be exempted from HCC surveillance after LT in a low AFP population. PIVKA-II may be a better predictor for explant microvascular invasion than AFP and could play a role in future models identifying LT candidates with the highest risk for HCC recurrence.
引言：目前，甲胎蛋白（AFP）和RETREAT评分被用于预测肝移植后肝细胞癌的复发。然而，对于低AFP人群，需要更优的鉴别模型。本研究旨在探讨在低AFP人群中，异常凝血酶原（PIVKA-II）对肝移植后无复发生存的预测价值，以及其对移植物微血管侵犯的预测作用。 方法：本研究采用回顾性队列研究设计，纳入1989年至2019年间在荷兰鹿特丹伊拉斯姆斯大学医学中心连续接受肝移植的所有肝细胞癌患者。在移植时收集的血清样本中测定AFP和PIVKA-II水平。从患者记录中获取肿瘤负荷和微血管侵犯的数据。 结果：研究队列共包括121例患者，其中15例（12.4%）出现肝细胞癌复发。AFP中位数为7.7 ng/mL（四分位距：4.4–20.2），PIVKA-II中位数为72.0 mAU/mL（四分位距：41.0–213.5）。在低AFP（≤8 ng/mL）和低PIVKA-II（≤90 mAU/mL）的患者中，5年无复发生存率为100%，而低AFP但高PIVKA-II的患者为85.7%（p=0.026）。无论AFP水平如何，符合米兰标准（基于移植物病理学）且PIVKA-II水平低的患者，其5年无复发生存率为100%，而高PIVKA-II水平的患者为81.1%（p=0.002）。在存在微血管侵犯的患者中，PIVKA-II的受试者工作特征曲线下面积略优于AFP（0.775 vs. 0.687）。 结论：在低AFP人群中，PIVKA-II ≤ 90 mAU/mL与AFP ≤ 8 ng/mL或符合米兰标准的患者相结合的双重模型，能够识别出在肝移植后无需进行肝细胞癌监测的患者群体。PIVKA-II在预测移植物微血管侵犯方面可能优于AFP，并可能在未来的模型中用于识别肝细胞癌复发风险最高的肝移植候选者。
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