Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, in part because of inadequate early detection strategies. Current recommendations for screening consist of semi-annual abdominal ultrasound with or without serum alpha-fetoprotein in patients with cirrhosis and in demographic subgroups with chronic hepatitis B infection. However, this screening strategy has several deficiencies, including suboptimal early-stage sensitivity, false positives with subsequent harms, inter-operator variability in ultrasound performance, and poor adherence. A blood-based biomarker with sufficient performance characteristics for early-stage disease could overcome several of these barriers to improving early-stage detection. However, prior to use of a biomarker for screening in clinical practice, a multistep validation is required in order to understand test performance characteristics. These steps include case-control validation, followed by validation in prospective cohorts of at-risk patients. Until recently, we lacked adequate longitudinal validation cohorts for early HCC detection; however, several validation cohorts are maturing, including the Hepatocellular Carcinoma Early Detection Study and the Texas Hepatocellular Carcinoma Consortium, which will allow for rigorous validation of candidate biomarkers. While there are several promising biomarkers awaiting validation, in order to supplant abdominal ultrasound, a candidate biomarker must show adequate test performance and overcome practical hurdles to ensure adoption in clinical practice. The promise of blood-based biomarkers is significant, especially given the limitations of ultrasound-based screening; however, they require adequate validation and several logistical obstacles must be overcome prior to clinical implementation.

肝细胞癌 (HCC) 是全世界癌症相关死亡的主要原因，部分原因是早期检测策略不足。目前的筛查建议包括对肝硬化患者和慢性乙型肝炎感染的人口学亚组每半年进行一次腹部超声检查，有或没有血清甲胎蛋白。然而，这种筛查策略有几个缺陷，包括早期敏感性不佳、假阳性和后续危害、超声性能的操作者间差异以及依从性差。具有足够的早期疾病性能特征的基于血液的生物标志物可以克服其中的几个障碍，以改善早期检测。然而，在临床实践中使用生物标志物进行筛查之前，为了了解测试性能特征，需要进行多步验证。这些步骤包括病例对照验证，然后在高危患者的前瞻性队列中进行验证。直到最近，我们还缺乏足够的纵向验证队列来进行早期 HCC 检测；然而，一些验证队列正在成熟，包括肝细胞癌早期检测研究和德克萨斯肝细胞癌联盟，这将允许对候选生物标志物进行严格验证。虽然有几种有前途的生物标志物等待验证，但为了取代腹部超声，候选生物标志物必须表现出足够的测试性能并克服实际障碍，以确保在临床实践中采用。基于血液的生物标志物的前景非常重要，特别是考虑到超声筛查的局限性；然而，它们需要充分的验证，并且在临床实施之前必须克服一些后勤障碍。