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肝细胞癌的先进监测策略:疗效与精准度的新时代。

Advancing Surveillance Strategies for Hepatocellular Carcinoma: A New Era of Efficacy and Precision.

作者信息

Singal Amit G, Ng Michelle, Kulkarni Anand

机构信息

Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.

Department of Hepatology, AIG Hospitals, Hyderabad, India.

出版信息

J Clin Exp Hepatol. 2024 Nov-Dec;14(6):101448. doi: 10.1016/j.jceh.2024.101448. Epub 2024 May 22.

Abstract

Hepatocellular carcinoma (HCC) is one of the few cancers with a 5-year survival that has remained below 20%; however, prognosis differs by tumor stage at diagnosis. Curative treatment options among patients with early-stage HCC afford a median survival of 5-10 years. Accordingly, international society guidelines recommend semi-annual HCC surveillance in at-risk patients, including those with cirrhosis or high-risk chronic hepatitis B infection. Surveillance is associated with increased early-stage HCC detection and curative treatments, leading to reduced HCC-related mortality. Abdominal ultrasound has been the cornerstone for HCC surveillance for the past two decades, but recent data have highlighted its suboptimal sensitivity for early-stage HCC detection, particularly in patients with obesity and those with non-viral etiologies of liver disease. The combination of ultrasound plus alpha fetoprotein (AFP) has higher sensitivity for early-stage HCC detection than ultrasound alone, although the combination still misses over one-third of HCC at an early stage. Emerging imaging and blood-based biomarker strategies have promising data in biomarker phase 2 (case-control) and phase 3 (cohort) studies. Beyond ultrasound, Magnetic resonance imaging (MRI) is the best-studied imaging strategy, with superior sensitivity and specificity compared to ultrasound in a cohort study. Abbreviated MRI protocols have been proposed to address concerns about MRI radiological capacity, costs, and patient acceptance. Of biomarker strategies, GALAD (a panel including gender, age, AFP, AFP-L3, and DCP) is the best validated, with promising sensitivity for early-stage HCC detection in a national multi-center cohort study. Liquid biopsy biomarkers, including methylated DNA markers, have also shown promising accuracy in case-control studies. Abbreviated MRI and GALAD are now entering prospective trials that examine clinical outcomes such as early-stage HCC detection and screening-related harms, which are essential data to understand for adoption in clinical practice. As additional surveillance strategies become available, it will allow an era of precision surveillance in which optimal surveillance modalities are tailored to individual patient risk and expected test performance.

摘要

肝细胞癌(HCC)是少数5年生存率仍低于20%的癌症之一;然而,其预后因诊断时的肿瘤分期而异。早期HCC患者的根治性治疗方案可使中位生存期达到5至10年。因此,国际社会指南建议对高危患者进行半年一次的HCC监测,包括肝硬化患者或慢性乙型肝炎高危感染者。监测与早期HCC检测及根治性治疗的增加相关,从而降低了HCC相关死亡率。在过去二十年中,腹部超声一直是HCC监测的基石,但最近的数据凸显了其在早期HCC检测方面的敏感性欠佳,尤其是在肥胖患者以及非病毒性肝病病因患者中。超声联合甲胎蛋白(AFP)对早期HCC检测的敏感性高于单纯超声,尽管该联合检测仍会漏诊超过三分之一的早期HCC。新兴的影像学和基于血液的生物标志物策略在生物标志物2期(病例对照)和3期(队列)研究中已有颇具前景的数据。除超声外,磁共振成像(MRI)是研究最多的成像策略,在一项队列研究中,其敏感性和特异性优于超声。已提出简化MRI方案以解决对MRI放射学能力、成本和患者接受度的担忧。在生物标志物策略中,GALAD(一个包括性别、年龄、AFP、AFP-L3和DCP的组合)得到了最佳验证,在一项全国多中心队列研究中对早期HCC检测具有颇具前景的敏感性。包括甲基化DNA标志物在内的液体活检生物标志物在病例对照研究中也显示出颇具前景的准确性。简化MRI和GALAD目前正在进入前瞻性试验,以检验诸如早期HCC检测和筛查相关危害等临床结果,这些是临床实践中采用所必须了解的关键数据。随着更多监测策略的出现,将开启一个精准监测的时代,即根据个体患者风险和预期检测性能量身定制最佳监测方式。

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