GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic Steatohepatitis
GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic Steatohepatitis
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DOI：
10.1016/j.cgh.2019.11.012
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发表时间：
2020-03-01
影响因子：
12.6
通讯作者：
Canbay, Ali
中科院分区：
文献类型：
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作者：
Best, Jan;Bechmann, Lars P.;Canbay, Ali
背景与目的：非酒精性脂肪性肝炎（NASH）相关肝细胞癌（HCC）的患病率正在增加。然而，在NASH患者中检测早期HCC的策略具有局限性。我们评估了GALAD评分的能力，该评分基于患者性别、年龄和甲胎蛋白（AFP）、AFP亚型L3（AFP-L3）和脱-γ-羧基凝血酶原（DCP）的血清水平来确定HCC的风险，以检测NASH患者中的HCC。我们对来自德国8个中心的125例HCC患者（20%符合米兰标准）和231例非HCC患者（NASH对照）进行了病例对照研究。我们比较了血清AFP、AFP-L3或DCP与GALAD评分在使用受试者工作特征曲线和相应曲线下面积（AUC）分析识别HCC患者方面的性能。我们还分析了日本389例接受HCC监测的NASH患者的数据，随访时间中位数为167个月。在5年的筛查期间，26例患者发生了HCC。为了补偿数据点的不规则间隔，我们进行了局部加权散点图平滑，线性回归和非线性曲线拟合，以评估HCC发展前GALAD的发展。GALAD评分确定任何阶段HCC患者的AUC为0.96 -显著高于血清AFP水平值（AUC，0.88）、AFP-L3（AUC，0.86）或DCP（AUC，0.87）。GALAD评分的AUC值在肝硬化患者（AUC，0.93）和无肝硬化患者（AUC，0.98）中一致。对于米兰标准内的HCC检测，GALAD评分达到0.91的AUC，在-0.63的临界值下，灵敏度为68%，特异性为95%。在一项初步日本队列研究中，早在HCC诊断前1.5年，发生HCC的NASH患者的平均GALAD评分高于未发生HCC的患者。GALAD评分高于-0.63大约200天前诊断hcch.CONCLUSIONS：在德国进行的病例对照研究和试点队列研究在日本，我们发现GALAD评分可以检测肝癌与NASH患者，有和没有肝硬化的准确性高。GALAD评分可以检测早期HCC患者，并可能有助于监测NASH患者，这些患者通常肥胖，这限制了超声检测肝癌的灵敏度。
BACKGROUND & AIMS: The prevalence of nonalcoholic steatohepatitis (NASH) associated hepatocellular carcinoma (HCC) is increasing. However, strategies for detection of early-stage HCC in patients with NASH have limitations. We assessed the ability of the GALAD score, which determines risk of HCC based on patient sex; age; and serum levels of alpha-fetoprotein (AFP), AFP isoform L3 (AFP-L3), and des-gamma-carboxy prothrombin (DCP), to detect HCC in patients with NASH.METHODS: We performed a case-control study of 125 patients with HCC (20% within Milan Criteria) and 231 patients without HCC (NASH controls) from 8 centers in Germany. We compared the performance of serum AFP, AFP-L3, or DCP vs GALAD score to identify patients with HCC using receiver operating characteristic curves and corresponding area under the curve (AUC) analyses. We also analyzed data from 389 patients with NASH under surveillance for HCC in Japan, followed for a median of 167 months. During the 5-year screening period, 26 patients developed HCC. To compensate for irregular intervals of data points, we performed locally weighted scatterplot smoothing, linear regression, and a non-linear curve fit to assess development of GALAD before HCC development.RESULTS: The GALAD score identified patients with any stage HCC with an AUC of 0.96 - significantly greater than values for serum levels of AFP (AUC, 0.88), AFP-L3 (AUC, 0.86) or DCP (AUC, 0.87). AUC values for the GALAD score were consistent in patients with cirrhosis (AUC, 0.93) and without cirrhosis (AUC, 0.98). For detection of HCC within Milan Criteria, the GALAD score achieved an AUC of 0.91, with a sensitivity of 68% and specificity of 95% at a cutoff of -0.63. In a pilot Japanese cohort study, the mean GALAD score was higher in patients with NASH who developed HCC than in those who did not develop HCC as early as 1.5 years before HCC diagnosis. GALAD scores were above -0.63 approximately 200 days before the diagnosis of HCC.CONCLUSIONS: In a case-control study performed in Germany and a pilot cohort study in Japan, we found the GALAD score may detect HCC with high levels of accuracy in patients with NASH, with and without cirrhosis. The GALAD score can detect patients with early-stage HCC, and might facilitate surveillance of patients with NASH, who are often obese, which limits the sensitivity of detection of liver cancer by ultrasound.