编者按：目前，肝脏超声检查和血清学甲胎蛋白（AFP）检测已作为肝硬化患者常规的肝癌筛查项目，然而，基于上述两项筛查的结果，肝癌风险仍存在变异。在刚刚结束的第十一届国际肝癌协会（ILCA）年会上，美国德克萨斯大学西南医学中心Amit Singal教授做了关于肝硬化肝癌患者精准筛查的专题报告。那么，我们能否在肝癌的早期筛查中获得更加精准的结果，本刊特邀Singal教授进行了专访。
《国际肝病》：目前，可应用于肝癌的早期诊断的分子主要有哪些？其临床应用价值如何？
Singal教授：目前肝癌的筛查策略仍然依赖于超声检查和AFP检测，而AFP仍是唯一一个通过验证的肝癌预测指标。此外，AFP-L3、DCP也是比较有前景的生物学标志物，但是仍有待进一步的验证。
《国际肝病》： 肝癌的精准诊断其实并不困难，而是难在肝癌的早期发现。目前是否有关于肝癌早期筛查的分子模型应用于临床？
Singal教授：这是个有趣的问题。谈到肝癌风险预测和分型，这也是精准筛查的一项重要内容。在丙型肝炎患者中，已有一种基于组织学水平的基因筛查可用于肝癌风险评估；而乙型肝炎作为非病毒性病因，这种筛查方法主要的局限性在于是一种基于组织的检查，具有侵袭性。目前正在进行血清学水平的研究，一旦成功它将给肝癌风险筛查带来巨大改观。
《国际肝病》：关于HCC的血清学指标其实挺多的，如何联合应用这些指标以提高对HCC的诊出是非常重要的课题。请您介绍一下相关的研究进展吗？
肝癌是一种高异质性的肿瘤，因此一种生物学标志物的检测可能不足以反映其肝癌风险，基于多种生物学标志物的肝癌筛查模型将弥补这一缺陷，这也是未来肝癌筛查的一个方向。GALAD评分系统是基于AFP、 AFP-L3 和 DCP三种生物学标志物的早期肝癌筛查模型，其临床应用仍有待在大规模的队列研究中进一步验证，这项工作目前正在进行当中，希望在不久的将来，这项肝癌筛查模型可以常规应用于临床。
原文链接：
Dr Singal: The talk I have given here at ILCA was on precision screening for hepatocellular carcinoma in patients with cirrhosis. The idea of the talk was that, right now, ultrasound and AFP are standard of care for HCC screening in patients with cirrhosis, however, we see that there is variation in HCC risk as well as the performance of these screening tests across patients. The question was whether we could do a better job of finding tests that would find cancer at an early stage in these patients.
Dr Singal: Right now, the current surveillance strategy for HCC is ultrasound with or without alpha-fetoprotein (AFP). There are five phases of biomarker development and AFP is currently the only biomarker that has gone through all of these phases of biomarker development and validation. When you take a look at the level of evidence, then I think that that is the best biomarker we have. We have several promising biomarkers - AFP-L3, DCP - but these are not necessarily as well validated as AFP.
Dr Singal: It is an interesting question. In terms of risk prediction and risk stratification, I think that is one of the key things in precision screening. There is a tissue-based gene signature that actually allows us to risk stratify patients. That has been shown in the hepatitis C population, the hepatitis B population, as well as non-viral etiologies, but the limitation of this approach is that it has historically been tissue-based. Work is currently going on to make this blood-based, and if that were to happen and we were then able to risk stratify patients, it would allow us to have precision screening in at-risk patients.
Dr Singal: Once again this relates to the GALAD score I mentioned, which combines three biomarkers (AFP, AFP-L3 and DCP). We know HCC is a heterogeneous tumor so it is likely that a single biomarker will not be sufficient. Biomarker panels and algorithms are the direction we should be heading in for the future. However, these biomarker algorithms are relatively new and require validation in large cohorts of patients. These studies are currently underway, and I am hoping over the next couple of years, they are really pushed forward in terms of data collection and become standard.