Background:Abdominal ultrasound is prone to hepatocellular carcinoma (HCC) surveillance failure, particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-associated liver disease (ALD), prompting growing interest in blood-based biomarkers as an alternative strategy.Methods:We conducted a case–control study evaluating two blood-based biomarker panels, GAAD and GALAD, for detection of early-stage HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 or A) in patients with MASLD or ALD cirrhosis. Blood specimens were collected within 6 months of HCC diagnosis (cases); controls were patients with cirrhosis but without HCC. GAAD and GALAD scores were measured using the Roche Elecsys platform, applying validated cutoffs of 2.57 and 2.47, respectively. Sensitivity and specificity were compared between the panels and versus ultrasound plus alpha fetoprotein (AFP) using McNemar’s chi square test.Results:Of 152 patients (56.6% men), 46.7% had HCC (54.9% BCLC 0/A) and 53.3% had cirrhosis without HCC. GAAD and GALAD each achieved a sensitivity of 87.2% for early-stage HCC, with specificities of 69.1% and 67.9%, respectively. In paired analyses (n = 90), GAAD had higher sensitivity for any-stage HCC (89.5% vs. 68.4%,p= 0.046) but lower specificity (71.8% vs. 93.0%,p= 0.006) than ultrasound plus AFP. GAAD and GALAD demonstrated consistently higher sensitivity than ultrasound plus AFP across subgroups by age, sex, cirrhosis etiology, and Child Pugh class.Conclusion:In this case–control study of patients with non-viral cirrhosis, GAAD and GALAD demonstrated high sensitivity for early-stage HCC. These findings highlight the potential of blood-based biomarkers to improve HCC surveillance in contemporary populations.
背景：腹部超声在肝细胞癌（HCC）监测中易出现漏诊，尤其在代谢功能障碍相关脂肪性肝病（MASLD）或酒精相关肝病（ALD）患者中更为明显，这促使基于血液的生物标志物作为替代策略受到日益关注。 方法：我们开展了一项病例对照研究，评估GAAD和GALAD两种血液生物标志物组合在MASLD或ALD肝硬化患者中检测早期HCC（巴塞罗那临床肝癌分期0期或A期）的效能。病例组在HCC确诊6个月内采集血样；对照组为肝硬化但未患HCC的患者。使用罗氏Elecsys平台检测GAAD和GALAD评分，分别采用已验证的截断值2.57和2.47。通过McNemar卡方检验比较两组标志物与超声联合甲胎蛋白（AFP）检测的敏感性和特异性。 结果：在152例患者（男性占56.6%）中，46.7%确诊HCC（其中54.9%为BCLC 0/A期），53.3%为无HCC的肝硬化患者。GAAD和GALAD对早期HCC的敏感性均为87.2%，特异性分别为69.1%和67.9%。在配对分析（n=90）中，对于任意分期HCC，GAAD的敏感性高于超声联合AFP（89.5% vs. 68.4%，p=0.046），但特异性较低（71.8% vs. 93.0%，p=0.006）。按年龄、性别、肝硬化病因及Child-Pugh分级分层分析显示，GAAD和GALAD在各亚组中均保持高于超声联合AFP的敏感性。 结论：在这项针对非病毒性肝硬化患者的病例对照研究中，GAAD和GALAD对早期HCC表现出高敏感性。这些发现凸显了血液生物标志物在改善当代人群HCC监测中的潜力。
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