Kim Do Young, Han Kwang-Hyub
Department of Internal Medicine, Yonsei University College of Medicine, Liver Cirrhosis Clinical Research Center, Liver Cancer Early Diagnosis Clinic, Severance Hospital, Seoul, Korea.
Liver Cancer. 2012 Jun;1(1):2-14. doi: 10.1159/000339016.
Hepatocellular carcinoma (HCC) is one of the most frequently occurring malignancies and has a high mortality rate. The incidence of HCC differs greatly according to the geographic area. East and Southeast Asia, as well as middle and West Africas have the highest prevalence of HCC. The risk factors for developing HCC are well known and include cirrhosis, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, alcohol consumption, smoking, diabetes, and nonalcoholic steatohepatitis. Cirrhosis is the most significant risk factor, and there is a correlation between the degree of noninvasively measured liver fibrosis and the risk of HCC occurrence. HBV exerts carcinogenic effects by several mechanisms, including host genome integration, and studies have revealed that HBV replication predicts HCC development. HCV induces multistep carcinogenesis from inflammation, to fibrosis and liver cancer. HCC is an appropriate target for surveillance programs for early cancer detection. Currently, liver ultrasonography (US) combined with serum alpha-fetoprotein (AFP, a biomarker of HCC) measurement every 6 months is the standard method of HCC surveillance. Although US is the most widely used tool, its sensitivity in detecting early HCC (i.e., within the Milan criteria) during surveillance is only 63%. AFP is the representative biomarker for both HCC surveillance and diagnosis; however, the unsatisfactory performance of AFP as a surveillance tool means that a novel biomarker or combination with other serum markers is required. Des-gamma-carboxy prothrombin and AFP-L3 are candidate biomarkers that are complementary to AFP. The strategies of HCC surveillance vary in different countries according to the healthcare system, the resources available, and health insurance coverage. Many studies have shown that the rate of early cancer detection and rate of application of curative therapies were increased, as was the survival time, by HCC surveillance, which should now become a part of standard care, rather than just a recommendation. Improved US technology and the discovery of new biomarkers are necessary to make further progress in HCC surveillance.
肝细胞癌(HCC)是最常见的恶性肿瘤之一,死亡率很高。HCC的发病率因地理区域而异。东亚和东南亚以及非洲中西部地区的HCC患病率最高。发生HCC的危险因素众所周知,包括肝硬化、乙型肝炎病毒(HBV)感染、丙型肝炎病毒(HCV)感染、饮酒、吸烟、糖尿病和非酒精性脂肪性肝炎。肝硬化是最重要的危险因素,非侵入性测量的肝纤维化程度与HCC发生风险之间存在相关性。HBV通过多种机制发挥致癌作用,包括宿主基因组整合,研究表明HBV复制可预测HCC的发展。HCV可诱导从炎症到纤维化再到肝癌的多步骤致癌过程。HCC是早期癌症检测监测计划的合适目标。目前,每6个月进行一次肝脏超声检查(US)并结合血清甲胎蛋白(AFP,一种HCC生物标志物)测量是HCC监测的标准方法。尽管US是使用最广泛的工具,但其在监测期间检测早期HCC(即符合米兰标准)的敏感性仅为63%。AFP是HCC监测和诊断的代表性生物标志物;然而,AFP作为监测工具的表现不尽人意,这意味着需要一种新的生物标志物或与其他血清标志物联合使用。去γ-羧基凝血酶原和AFP-L3是与AFP互补的候选生物标志物。HCC监测策略在不同国家因医疗保健系统、可用资源和医疗保险覆盖范围而异。许多研究表明,通过HCC监测,早期癌症检测率和治愈性治疗的应用率有所提高,生存时间也有所延长,现在HCC监测应成为标准治疗的一部分,而不仅仅是一项建议。改进US技术和发现新的生物标志物对于HCC监测取得进一步进展至关重要。