Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Hepatology. 2022 Mar;75(3):541-549. doi: 10.1002/hep.32185. Epub 2021 Dec 17.
Most patients with HCC are diagnosed at a late stage, highlighting the need for more accurate surveillance tests. Although biomarkers for HCC early detection have promising data in Phase 2 case-control studies, evaluation in cohort studies is critical prior to adoption in practice. We leveraged a prospective cohort of patients with Child-Pugh A or B cirrhosis who were followed until incident HCC, liver transplantation, death, or loss to follow-up. We used a prospective specimen collection, retrospective, blinded evaluation design for biomarker evaluation of GALAD (gender × age × log alpha-fetoprotein [AFP] × des-gamma-carboxy prothrombin), longitudinal GALAD, and the HCC Early Detection Screening (HES) algorithm-compared to AFP-using patient-level sensitivity and screening-level specificity.
Of 397 patients with cirrhosis, 42 developed HCC (57.1% early stage) over a median of 2.0 years. Longitudinal GALAD had the highest c-statistic for HCC detection (0.85; 95% CI, 0.77-0.92) compared to single-time point GALAD (0.79; 95% CI, 0.71-0.87), AFP (0.77; 95% CI, 0.69-0.85), and HES (0.76; 95% CI, 0.67-0.83). When specificity was fixed at 90%, the sensitivity for HCC of single-time point and longitudinal GALAD was 54.8% and 66.7%, respectively, compared to 40.5% for AFP. Sensitivity for HCC detection was higher when restricted to patients with biomarker assessment within 6 months prior to HCC diagnosis, with the highest sensitivities observed for single-time point GALAD (72.0%) and longitudinal GALAD (64.0%), respectively. Sensitivity of single-time point and longitudinal GALAD for early-stage HCC was 53.8% and 69.2%, respectively.
GALAD demonstrated high sensitivity for HCC detection in a cohort of patients with cirrhosis. Validation of these results is warranted in large Phase 3 data sets.
大多数 HCC 患者在晚期被诊断出来，这突出表明需要更准确的监测测试。尽管 HCC 早期检测的生物标志物在 2 期病例对照研究中具有有前途的数据，但在实际应用之前，在队列研究中进行评估至关重要。我们利用了一组前瞻性的 Child-Pugh A 或 B 肝硬化患者队列，这些患者一直随访到 HCC、肝移植、死亡或失访。我们使用前瞻性标本采集、回顾性、盲法评估设计来评估 GALAD（性别×年龄×对数 AFP×脱γ-羧基凝血酶原）、纵向 GALAD 和 HCC 早期检测筛查（HES）算法，与 AFP 相比，使用患者水平的敏感性和筛查水平的特异性。
在 397 名肝硬化患者中，42 名患者在中位 2.0 年内发展为 HCC（57.1%为早期）。与单次 GALAD（0.79；95%CI，0.71-0.87）、AFP（0.77；95%CI，0.69-0.85）和 HES（0.76；95%CI，0.67-0.83）相比，纵向 GALAD 对 HCC 检测的 AUC 最高（0.85；95%CI，0.77-0.92）。当特异性固定在 90%时，单次和纵向 GALAD 对 HCC 的敏感性分别为 54.8%和 66.7%，而 AFP 为 40.5%。当将生物标志物评估限制在 HCC 诊断前 6 个月内进行时，对 HCC 的检测敏感性更高，单次和纵向 GALAD 的最高敏感性分别为 72.0%和 64.0%。单次和纵向 GALAD 对早期 HCC 的敏感性分别为 53.8%和 69.2%。
GALAD 在肝硬化患者队列中对 HCC 的检测具有很高的敏感性。需要在大型 3 期数据集中验证这些结果。
