A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis.

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.

GALAD评分（性别、年龄、α-胎儿蛋白[AFP] L3、AFP和脱-γ羧基凝血酶原）在第二阶段研究中显示出对HCC具有极高的敏感性和特异性。

We performed a phase 3 biomarker validation study to compare GALAD with AFP in detecting HCC.

我们进行了一项III期生物标志物验证研究，比较GALAD与AFP在检测HCC中的效果。

Methods

This is a prospective study of patients with cirrhosis enrolled at 7 centers.

这是一项前瞻性研究，研究对象为在7个中心登记的肝硬化患者。

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.

在每个监测点每6个月进行一次肝细胞癌（HCC）的监测，并根据美国肝脏研究学会的指南确认HCC的诊断。

Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository.

在每次随访访问时获取用于生物标志物研究的血液样本，并将其储存在生物样本库中。

Measurements of AFP, AFP-L3, and des-γ carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data.

在富士胶片实验室由对临床数据不知情的工作人员进行了甲胎蛋白（AFP）、AFP-L3和脱-γ羧基凝血酶原的测量。

The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months before the clinical diagnosis.

在临床诊断前12个月内，回顾性评估了GALAD在检测肝细胞癌（HCC）中的性能。

All analyses were conducted by an unblinded statistician in the Early Detection Research Network data management and coordinating center.

所有分析均由早期检测研究网络数据管理和协调中心的一位未盲统计师进行。

Results

A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years.

共有1,558名肝硬化患者被纳入研究，并随访了中位数为2.2年。

A total of 109 patients developed HCC (76 very early or early stage), with an annual incident rate of 2.4%.

共有109名患者发展为肝细胞癌（其中76名为非常早期或早期阶段），年发病率为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.

在肝细胞癌发生前12个月内的甲胎蛋白（AFP）和GALAD评分曲线下面积分别为0.66和0.78（P < .001）。

Using a cutoff for GALAD of -1.36, the specificity was 82%, and the sensitivity at 12 months before HCC diagnosis was 62%.

使用GALAD评分-1.36作为截断值，其特异性为82%，在肝细胞癌（HCC）诊断前12个月的敏感性为62%。

For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months before HCC diagnosis (P = .001).

相比之下，在82%的特异性下，甲胎蛋白（AFP）在肝细胞癌（HCC）诊断前12个月的敏感性为41%（P = .001）。

Conclusions

GALAD score, compared to AFP, improves the detection of HCC within 12 months before the actual diagnosis.

与甲胎蛋白（AFP）相比，GALAD评分在实际诊断前12个月内提高了对肝细胞癌（HCC）的检出率。