3期生物标志物对肝硬化检测肝癌检测的生物标志物验证
A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis
影响因子:25.10000
分区:医学1区 Top / 胃肠肝病学1区
发表日期:2025 Feb
作者:
Tracey L Marsh, Neehar D Parikh, Lewis R Roberts, Myron E Schwartz, Mindie H Nguyen, Alex Befeler, Stephanie Page-Lester, Nabihah Tayob, Sudhir Srivastava, Jo Ann Rinaudo, Amit G Singal, K Rajender Reddy, Jorge A Marrero
摘要
需要对肝细胞癌（HCC）进行更好的监视测试。在2阶段研究中，galad评分（性别，年龄，α-五蛋白[AFP] L3，AFP和DES-γ羧基凝血酶）对HCC具有出色的敏感性和特异性。我们进行了3期生物标志物验证研究，以将galad与AFP进行比较，以检测HCC。这是对7个中心纳入肝硬化患者的前瞻性研究。在每个站点每6个月进行一次HCC的监视，根据美国研究肝脏疾病指南的协会确认HCC诊断。每次随访访问中都会获得用于生物标志物研究的血液，并存储在生物库中。 AFP，AFP-L3和DES-γ羧基凝血酶的测量是由对临床数据看不见的工作人员在Fujifilm实验室中进行的。在临床诊断前的12个月内回顾性评估了galad检测HCC中的表现。所有分析均由一位未盲目的统计学家在早期检测研究网络数据管理和协调中心进行。总共招募了1,558例肝硬化患者，并遵循2。2年的中位数。共有109例患者患有HCC（76个早期或早期），年度事件率为2.4％。在HCC前的12个月内，AFP和GALAD的曲线面积分别为0.66和0.78（p <.001）。使用-1.36的galad截止，特异性为82％，在HCC诊断前12个月的灵敏度为62％。为了进行比较，在82％特异性时的AFP的性能显示在HCC诊断前12个月时的灵敏度为41％（P = .001）。与AFP相比，Galad评分可在实际诊断前的12个月内提高HCC的检测。
Abstract
Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score (gender, age, α-fetoprotein [AFP] L3, AFP, and des-γ carboxyprothrombin) has been shown to have excellent sensitivity and specificity for HCC in phase 2 studies. We performed a phase 3 biomarker validation study to compare GALAD with AFP in detecting HCC.This is a prospective study of patients with cirrhosis enrolled at 7 centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per American Association for the Study of Liver Diseases guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and des-γ carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months before the clinical diagnosis. All analyses were conducted by an unblinded statistician in the Early Detection Research Network data management and coordinating center.A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage), with an annual incident rate of 2.4%. The areas under the curve for AFP and GALAD within 12 months before HCC were 0.66 and 0.78 (P < .001), respectively. Using a cutoff for GALAD of -1.36, the specificity was 82%, and the sensitivity at 12 months before HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months before HCC diagnosis (P = .001).GALAD score, compared to AFP, improves the detection of HCC within 12 months before the actual diagnosis.