Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Department of Biostatistics, Dana Farber Cancer Center, Boston, MA, USA.
J Hepatol. 2023 Jan;78(1):207-216. doi: 10.1016/j.jhep.2022.08.036. Epub 2022 Sep 8.
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) 是全球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具有慢性乙型肝炎感染的特定人群进行半年一次的腹部超声检查，或联合血清甲胎蛋白检查。然而，这种筛查策略存在几个缺陷，包括早期敏感性不足、后续危害的假阳性、超声性能的操作者间差异以及较差的依从性。具有足够早期疾病性能特征的基于血液的生物标志物可以克服这些提高早期检测的障碍。然而，在将生物标志物用于临床实践之前，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，然后是高危患者的前瞻性队列验证。直到最近，我们缺乏足够的用于早期 HCC 检测的纵向验证队列；然而，有几个验证队列正在成熟，包括肝细胞癌早期检测研究和德克萨斯州肝细胞癌联盟，这将允许对候选生物标志物进行严格验证。虽然有几个有前途的生物标志物正在等待验证，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的采用。基于血液的生物标志物的前景非常广阔，尤其是鉴于超声筛查的局限性；然而，在临床实施之前，它们需要进行充分的验证，并且必须克服几个后勤障碍。
