Wang Chun-Hsiang, Wey Keh-Cherng, Mo Lein-Ray, Chang Kuo-Kwan, Lin Ruey-Chang, Kuo Jen-Juan
Department of Hepatogastroenterology, Tainan Municipal Hospital, Tainan, Taiwan E-mail :
Asian Pac J Cancer Prev. 2015;16(9):3595-604. doi: 10.7314/apjcp.2015.16.9.3595.
Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), des- carboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.
肝细胞癌(HCC)一直是全球最致命的恶性肿瘤之一,其相关的发病率和死亡率仍然备受关注。基于对HCC血清学诊断的深入综述,除甲胎蛋白(AFP)外,还有其他生物标志物:豆凝集素反应性AFP(AFP-L3)、脱羧凝血酶原(DCP)、具有免疫球蛋白和表皮生长因子(EGF)同源结构域2的酪氨酸激酶(TIE2)表达单核细胞(TEMs)、磷脂酰肌醇蛋白聚糖-3(GPC3)、高尔基体蛋白73(GP73)、白细胞介素-6(IL-6)以及鳞状细胞癌抗原(SCCA)已被提议作为HCC早期检测的生物标志物。HCC的诊断主要基于非侵入性标准成像方法,如超声(US)、动态多期多层螺旋CT(MDCT)和磁共振成像(MRI)。一些专家主张钆塞酸二钠(Gd-EOB-DTPA)MRI和对比增强超声作为有前景的首选成像方式。关于组织标志物的最新进展,许多使用全基因组DNA微阵列、qRT-PCR以及蛋白质组学和免疫染色研究的前沿技术已被应用,试图识别HCC早期诊断的标志物。初诊时只有不到一半的HCC患者处于可通过局部消融、手术切除或肝移植等治愈性方案治疗的早期阶段。经动脉化疗栓塞术(TACE)被认为是中期HCC姑息治疗的标准疗法。最近使用载药微球的创新程序和使用钇-90的放射性栓塞术可能在HCC治疗中显示出有益效果。在过去几年中,几种分子靶向药物已在晚期HCC的临床试验中进行了评估。索拉非尼是目前唯一被批准用于HCC的全身治疗药物。它已被批准用于治疗肝功能良好、无症状且不适合进行手术切除或肝移植等潜在治愈性治疗的HCC患者。在美国、欧洲尤其是日本,丙型肝炎病毒(HCV)相关的HCC占大多数肝癌病例,而在亚太地区,乙型肝炎病毒(HBV)可能在HCC发展中发挥更重要的作用。乙肝疫苗接种(目前尚无丙肝疫苗)已被公认为预防HBV相关HCC的最佳一级预防方法,尽管对于已经感染HBV或HCV的患者,抗病毒治疗的二级预防仍然是一种合理的策略。除了HBV和HCV,还应关注其他相关的HCC危险因素,包括因肥胖和糖尿病导致的非酒精性脂肪性肝病、大量饮酒以及长期接触黄曲霉毒素。有趣的是,咖啡和维生素K2已被证明对HCC有保护作用。关于手术切除后HCC复发的三级预防,添加抗病毒治疗已被证明是一种合理的策略。