编者按：肝细胞癌（HCC）是全球癌症死亡的主要原因，尤其是在亚洲。目前的监测标准建议超声联合甲胎蛋白，但超声在晚期肝硬化或肥胖患者中的有效性显著降低，且结果易受医师诊断水平影响。近日，有研究特别探索了多种生物标志物血液检测用于代偿期肝硬化患者HCC监测的作用，并分析了各风险监测模型的成本-效益，以期提高临床应用可行性。

 

第33届亚太肝脏研究学会年会（APASL 2024）“大师前沿讲座（State-of-the Art Lecture）”专题上， 泰国国立玛西隆大学诗里叻医学院肝病专家Tawesak Tanwandee教授发表了题为“HCC监测: 血液生物标志物检测能否取代超声检查”的主题报告，《国际肝病》有幸在大会现场邀请到Tawesak Tanwandee教授就HCC监测做进一步的专访，精彩内容分享如下。

 

《国际肝病》

亚太地区肝癌疾病负担重，对高危人群进行肝细胞癌（HCC）筛查和监测是实现早诊早治、改善患者预后的重要前提。近年来，基于血液的生物标志物HCC监测显示出较传统超声检查更好的灵敏度、特异度和简便性。能否请您介绍亚太地区目前主要应用的血液检测标志物和评分模型？

 

Tawesak Tanwandee教授：HCC是亚太地区的头号癌症杀手之一，由于所有这些患者通常在疾病晚期才出现症状，因此早期发现非常关键。在很多国家，超声检查虽然可及但等待时间很长，因此我们正在寻找相关的生物标志物，比如基于血液的生物标志物可以作为除了超声检查外的筛查工具，甚至替代超声检查作为HCC监测的标准检测方法。

 

最近有研究探索了多种基于血液检测的生物标志物在HCC监测方面的应用，结果表明其在代偿期肝硬化患者中应用更为广泛，包括已上市可及的检测，例如AFP-L3、PIVKA-Ⅱ，以及基于这些生物标志物构建的算法，如GALAD评分和GAAD评分，这些算法对早期癌症检测有更优的灵敏度和特异度。然而，尽管基于血液的HCC监测看起来很有希望，提供更高的灵敏度并减少解释偏差，但其取代超声作为标准检测方法的有效性需要在真实世界的应用中进一步验证。

 

<Hepatology Digest>: The burden of liver cancer in the Asia Pacific region is heavy, and screen and monitoring of hepatocellular carcinoma in high-risk relations is an important pursuit for achieving early diagnosis and treatment and improving patient prognoses. In recent years, blood-based biomarkers for HCC surveillance have shown better sensitivity. So, could you please introduce the currently used blood testing biomarkers and scoring models in the Asia pacific region?

 

Dr. Tawesak Tanwandee: HCC is among the top cancer killer in Asia Pacific country, especially in our region, where most of the people presented at the late state. So, the early detection is going to be the big issue. Since all of these patients, usually they are asymptomatic until very late in disease, so early detection could be the key. And then in many countries where ultrasound is available, but the wait time for the ultrasound is long. That's why we are looking for biomarkers like blood-based biomarker or biomarker panels that can be implemented at the screening tool and in addition to ultrasound or replacement of the ultrasound. Recent studies have explored multi-biomarker blood tests for HCC surveillance, especially in compensated cirrhosis patients. These include biomarkers like AFP-L3, PIVKAII which are commercially available, and algorithms derived by these biomarkers such as GALAD, GAAD score which had shown more sensitive and quite specific for early cancer detections. However, while blood-based HCC surveillance appears promising, offering increased sensitivity and reduced interpretative bias, its efficacy in replacing ultrasound as the standard practice requires further validation in real-world applications.

 

《国际肝病》

从这些标志物在亚太地区的临床实际应用看，其效能如何？尚存在哪些亟待解决的问题？

 

Tawesak Tanwandee教授：基于血液生物标志物的好处是不同的标志物可以使用相同的血液，在一些生物标志物中，可以使用相同的机器进行化学测试，但在另一些生物标志物中，需要有新安装的专属机器。目前生物标志物的广泛应用存在两个主要问题，首先是机器的可用性，许多医院没有可用检测血液生物标志物的机器。其次，高昂的检测成本是由政府报销还是患者自己来支付尚未解决。当然，说服政府来报销这些检测费用可能是一个很大的挑战，但我们仍然需要这样做来让患者有更大的获益并改善患者的预后。

 

<Hepatology Digest>: From the perspective of the practical application of these markers, in the Asia Pacific region, what are their efficacies? And what are the problems that need to be solved urgently?

 

Dr. Tawesak Tanwandee: The good thing for biomarkers is that they use the same blood. So in some biomarkers, they can use the same machine for chemistry tests. But in some biomarkers, they have proprietary machine that you need to install new. The problem for biomarkers nowadays is two things. Firstly, it is the availability of the machines. In many hospitals, they do not have the machine available. And secondly, it is the cost that's going to be added to the cost of testing. So whether the government or the patient themselves come to reimburse or pay for this cost? We need to convince the government to reimburse us for these biomarkers. This could be a big challenge, but we need to do it in order to improve our patients’ outcome.

 

《国际肝病》

总体而言，您认为基于血液的生物标志物用于HCC监测的前景如何？未来是否会取代超声检查？

 

Tawesak Tanwandee教授：一些其他肿瘤的监测中可以用基于血液的生物标志物代替影像学或内镜检查。随着新一代PCR和基于DNA筛查的出现，希望生物标志物检测能够尽快取代标准检测方法超声检查，但这需要一定的时间。目前还未到生物标志物应用的黄金时期，还需要进行大规模的前瞻性临床研究，包括大量的样本，以及对病例的持续跟踪，然后将生物标志物与标准方法进行比较，看看哪一个可能更好。如果大规模的循证医学试验显示生物标志物有更好的结果，则可考虑取代。

 

<Hepatology Digest>: What do you think are the prospects of blood based biomarkers for HCC surveillance? Will they replace ultrasound in the future?

 

Dr. Tawesak Tanwandee: I hope so. I think there are some examples of other tumors that can use blood-based biomarkers replacing the imaging or colonoscopy. With the availability of next generation PCR and the DNA based screening, I hope that this can replace the previous ultrasound as soon as possible, but it needs some times. It is not a prime time for implementing biomarker nowadays. Because we need to perform large phase tree study that include huge samples, and follow them prospectively, then compare biomarkers with standard care to see which one could be better. If large evidence-based trials show better results for the biomarkers, there will be new problems. By that time, we did not perform ultrasound, but with the availability of ultrasound everywhere, people can go out there and perform ultrasound by themselves. So it's going be contamination of the test.

 

《国际肝病》

最后，请您谈谈本届年会上，HCC监测领域的重磅研究？或者较受启发的前沿观点？

 

Tawesak Tanwandee教授：目前特别是在亚太国家，HCC监测领域最大的启发是基于血液生物标志物的应用实施。在日本，除了超声检查外，一直在使用这种基于血液的生物标志物进行HCC监测。在中国，也开始使用基于血液的生物标志物进行监测。在许多其他国家，也即将有可用的基于血液的生物标志物监测方法。随着基于血液生物标志物的广泛使用，虽然可能没有预期严格的大规模前瞻性临床试验，但在真实世界的实践中，通过患者的不断积累至少可以增加监测项目的有效数据。在部分国家或地区已经通过这种方式解决了HCC监测的相关问题。

 

<Hepatology Digest>: Could you talk about the blockbuster research in the field of HCC surveillance at this annual meeting, or the inspirational frontier ideas at this conference?

 

Dr. Tawesak Tanwandee: I think the inspiration for the HCC screening nowadays, especially in Asia Pacific country, is the implementations of blood-based biomarker. In Japan, they have been using these kinds of blood-based biomarkers in addition to the ultrasound. In China, they also start to use the blood-based biomarkers. And in many countries, we are going to have these kinds of blood-based biomarkers available. Then with the widespread use of the blood-based biomarkers, although we don't have the prospective critical rise and thrive, but with the real world practice, we can at least add benefits to the surveillance program by the patients who come to us. This has already helped out the surveillance in my country.

 

（来源：《国际肝病》编辑部）

 

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