Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Hepatol Commun. 2024 Nov 4;8(11). doi: 10.1097/HC9.0000000000000565. eCollection 2024 Nov 1.
Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice.
The National Liver Cancer Screening Trial is an adaptive pragmatic randomized phase IV trial, which began enrollment in January 2024, comparing ultrasound-based versus biomarker-based screening in 5500 patients with chronic hepatitis B infection or cirrhosis from any etiology. Eligible patients are randomly assigned in a 1:1 ratio to semi-annual screening with ultrasound ± alpha-fetoprotein (arm A) or semi-annual screening with GALAD (arm B). Randomization is stratified by enrollment site, liver disease severity (per Child-Pugh class), liver disease etiology (viral, nonviral, and noncirrhotic HBV), and sex. Patients are being recruited from 15 sites (a mix of tertiary care academic referral centers, safety-net health systems, and large community health systems) over a 3-year period, and the primary endpoint, reduction in late-stage HCC, will be assessed at the end of year 5.5.
The results of this trial will inform the best strategy for HCC screening and early-stage detection in patients with chronic liver diseases. If GALAD shows superiority, HCC screening would primarily shift from an ultrasound-based strategy to the adoption of the biomarker panel.
NCT06084234.
The TRACER Study is actively enrolling.
专业指南建议使用半年一次的超声联合或不联合甲胎蛋白（AFP）对高危患者进行 HCC 筛查；然而，由于依从性和敏感性低，该策略效果有限。越来越多的数据支持基于血液的生物标志物组合的潜在作用，这可能会改善这两个方面。生物标志物组合 GALAD 由性别、年龄和 3 种血液生物标志物（AFP、AFP-L3 和脱羧凝血酶原）组成，在生物标志物 II 期（病例对照）和 III 期（回顾性队列）验证研究中显示出了较高的敏感性和特异性。然而，在将其应用于实践之前，需要在大型 IV 期生物标志物临床实用研究中进行前瞻性验证。
国家肝癌筛查试验是一项适应性实用随机 IV 期试验，于 2024 年 1 月开始入组，比较了 5500 例慢性乙型肝炎感染或任何病因引起的肝硬化患者的基于超声与基于生物标志物的筛查。符合条件的患者以 1:1 的比例随机分配至半年一次的超声联合 AFP（A 组）或半年一次的 GALAD 筛查（B 组）。随机分组按入组地点、肝脏疾病严重程度（按 Child-Pugh 分级）、肝脏疾病病因（病毒、非病毒和非肝硬化 HBV）和性别分层。该试验正在 15 个地点（包括三级保健学术转诊中心、保障医疗体系和大型社区卫生系统）进行为期 3 年的招募，主要终点即晚期 HCC 减少的评估时间为第 5.5 年末。
该试验的结果将为慢性肝病患者的 HCC 筛查和早期发现提供最佳策略。如果 GALAD 显示出优越性，HCC 筛查将主要从基于超声的策略转变为采用生物标志物组合。
NCT06084234。
TRACER 研究正在积极招募中。
