Department of Medical Sciences, University of Turin, Turin, Italy -
Department of Medical Sciences, University of Turin, Turin, Italy.
Panminerva Med. 2017 Dec;59(4):283-289. doi: 10.23736/S0031-0808.17.03353-5. Epub 2017 Jun 23.
Reliable biomarkers for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis are lacking. We evaluated the use of miR-122, alpha-fetoprotein (AFP) and protein induced by vitamin k absence/antagonist II (PIVKA-II) for HCC risk prediction in patients with HBV-related cirrhosis under surveillance.
We first analyzed a group of 63 patients with HBV-related liver cirrhosis of whom 33 had HCC. Then we performed a retrospective analysis on another group of 13 cirrhotic patients who developed HCC during surveillance, of whom serial serum samples were available (at time of HCC diagnosis [T0], 6-9 months [T-1] and 12-18 months [T-2] before HCC detection). Serum miR-122 levels were assessed by quantitative real time-PCR, whereas AFP and PIVKA-II were measured by fully automated chemiluminescent enzyme immunoassay.
Serum levels of miR-122, AFP and PIVKA-II were different between patients with cirrhosis and those with HCC (P=0.024, P<0.001 and P<0.001, respectively). Areas under the curve (AUC) were 0.675 for miR-122, 0.791 for AFP and 0.846 for PIVKA-II, while their combination improved the discrimination power between cirrhosis and HCC (AUC=0.918). In the longitudinal study, we found a significant variation overtime for the biomarkers combination (P=0.011) but not for each single biomarker (miR-122, P=0.163; AFP, P=0.170; PIVKA-II, P=0.447). Combined miR-122+AFP+PIVKA-II adjusted Hazard Ratio for HCC development was 10.63, 95% confidence interval 1.87-60.28 (P<0.001).
In HBV-related cirrhosis, the combination of miR-122, AFP and PIVKA-II enables the identification of patients at higher risk of HCC development that could benefit from closer monitoring.
目前缺乏可靠的生物标志物来早期检测肝硬化患者的肝细胞癌（HCC）。我们评估了 miR-122、甲胎蛋白（AFP）和维生素 K 拮抗剂 II 诱导蛋白（PIVKA-II）在接受监测的乙型肝炎病毒（HBV）相关肝硬化患者中的 HCC 风险预测中的应用。
我们首先分析了一组 63 例 HBV 相关肝硬化患者，其中 33 例患者患有 HCC。然后，我们对另一组 13 例在监测期间发生 HCC 的肝硬化患者进行了回顾性分析，这些患者的连续血清样本可用（在 HCC 诊断时[T0]、6-9 个月[T-1]和 12-18 个月[T-2]前 HCC 检测）。通过实时定量 PCR 评估血清 miR-122 水平，而 AFP 和 PIVKA-II 通过全自动化学发光酶免疫测定法进行测量。
肝硬化患者和 HCC 患者的血清 miR-122、AFP 和 PIVKA-II 水平不同（P=0.024、P<0.001 和 P<0.001）。miR-122 的 AUC 为 0.675，AFP 的 AUC 为 0.791，PIVKA-II 的 AUC 为 0.846，而它们的组合提高了肝硬化和 HCC 之间的区分能力（AUC=0.918）。在纵向研究中，我们发现标志物组合的时间变化具有统计学意义（P=0.011），但每个单一标志物的变化均无统计学意义（miR-122，P=0.163；AFP，P=0.170；PIVKA-II，P=0.447）。调整 HCC 发展风险的 miR-122+AFP+PIVKA-II 联合风险比为 10.63，95%置信区间为 1.87-60.28（P<0.001）。
在 HBV 相关肝硬化中，miR-122、AFP 和 PIVKA-II 的组合可识别出 HCC 发展风险较高的患者，这些患者可能受益于更密切的监测。
