GALAD生物标志物在肝硬化中检测肝细胞癌的三期验证研究
A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis
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影响因子:25.1
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
DOI:
10.1053/j.gastro.2024.09.008
摘要
需要更优的肝细胞癌（HCC）监测检测方法。GALAD评分（性别、年龄、α-胎蛋白[AFP] L3、AFP以及去γ-羧酶前凝血酶原）在第二阶段研究中已显示出卓越的敏感性和特异性。我们进行了一项三期生物标志物验证研究，将GALAD与AFP在HCC检测中的表现进行比较。本研究为一项前瞻性研究，纳入7个中心的肝硬化患者。每6个月在每个中心进行HCC的监测，HCC诊断依据美国肝病研究协会指南确认。在每次随访中采集血样用于生物标志物研究，并存储于生物库中。AFP、AFP-L3和去γ-羧酶前凝血酶原的测量由富士胶片实验室的工作人员在盲法条件下完成。GALAD在临床诊断前12个月检测HCC的表现进行了回顾性评估。所有分析由早期检测研究网络数据管理与协调中心的未盲统计学家进行。共入组1558名肝硬化患者，随访中位时间为2.2年。其中109名患者发展为HCC（76例为极早或早期），年发病率为2.4%。在HCC发生前12个月内，AFP的曲线下面积为0.66，GALAD为0.78（P < .001）。以-1.36为GALAD的临界值，其特异性为82%，在HCC诊断前12个月的敏感性为62%。对比之下，AFP在82%特异性下的表现为在HCC诊断前12个月的敏感性为41%（P = .001）。与AFP相比，GALAD评分在诊断前12个月内更有效地检测HCC。
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.