Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era?
Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era?
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DOI：
10.1016/j.jhep.2022.08.036
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发表时间：
2023-01
影响因子：
25.7
通讯作者：
Singal, Amit G.
中科院分区：
文献类型：
--
作者：
Parikh, Neehar D.;Tayob, Nabihah;Singal, Amit G.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因，部分原因是早期发现策略不充分。目前推荐的筛查方法包括：在肝硬化患者和慢性乙型肝炎感染的人口统计学亚组中，每半年进行一次有或没有血清甲胎蛋白的腹部超声检查。然而，这种筛查策略存在一些不足，包括早期敏感性不佳、假阳性导致后续危害、超声表现的操作者之间的差异以及较差的依从性。一种基于血液的生物标志物具有足够的早期疾病性能特征，可以克服这些障碍，提高早期检测水平。然而，在临床实践中使用生物标志物进行筛选之前，需要进行多步骤验证，以了解测试性能特征。这些步骤包括病例对照验证，然后在有风险患者的前瞻性队列中进行验证。直到最近，我们缺乏足够的早期HCC检测的纵向验证队列；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的验证。虽然有一些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被采用。基于血液的生物标志物的前景是显著的，特别是考虑到基于超声波筛查的局限性；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。
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.
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