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HCC监测

采用完善的监测策略对HCC高危患者进行密切监测,则可以及早检出肝细胞癌(HCC),并施行治愈性治疗。使用肿瘤标记物(甲胎蛋白异质体(AFP-L3)和异常凝血酶原(PIVKA II)进行监测可以提高检出早期HCC的几率。

HCC监测改善患者预后

HCC的早期监测对于治愈性治疗的应用和患者预后的改善至关重要。因为HCC的病因通常是可鉴别的,因此强烈建议HCC高危患者参考HCC早期监测项目,以便及早检出HCC[1]

2008年,一项在美国开展的HCC监测研究得出以下结论:对肝硬化患者进行的监测项目可以识别早期HCC,HCC监测提高了接受早期治疗的HCC患者的长期无肿瘤生存率[2]

国际肝病权威组织认为肝硬化患者和慢性乙肝/丙肝患者发展为HCC的风险很高[3-5]。他们建议高危患者参加HCC监测项目,以便及早发现HCC。

在早期阶段发现HCC肿瘤大大拓宽了可以治愈性治疗方法的选择范围,诸如切除术,射频消融和移植。这些治疗后的5年生存率可以超过50%[6]。晚期HCC患者可选择的治疗方案仅限于保守治疗,例如化疗栓塞和索拉菲尼,这些治疗对患者存活率的影响微乎其微。

需要更好的监测策略

在可以采取治愈性治疗时,监测的质量会影响发现早期HCC的能力。

2010年在美国开展的一项研究表明,在发展为HCC的肝硬化患者中,只有不到20%的人接受了常规定期监测[1]

美国肝病研究协会(AASLD)的指导原则建议,高危患者应每隔6个月用超声筛查一次[6]。然而,若仅使用超声监测慢性肝病患者可能因为许多小肿瘤未能被发现而无法检出HCC[1]

超声检测高度依赖当时操作人员的经验和专业知识,与其灵敏度直接相关。当用于肥胖或具有严重肝硬化的患者时,超声波的性能可能进一步受限。超声灵敏度介于44%至80%之间,特异度超过90%[6,7]

由美国顶级护理中心组成的长期治疗丙肝病毒抵抗肝硬化试验(HALT-C)研究组,其开展的回顾性研究发现,在发展为HCC的患者中,只有20%的病人出现2厘米或2厘米以下的肿瘤,超过四分之一的肿瘤超出了米兰标准[8]

日本肝病学会(JSH)的HCC管理指南包括肿瘤标记物检测(AFP,AFP-L3和PIVKA II)[8]。日本2010年度监测效果调查报告得出结论,在所有HCC患者中,33.5%的患者肿瘤为≦2cm,超过62%已接受手术或局部消融治疗,治疗方案仅适用于早期HCC[9]

HCC监测的推荐标准

美国
AASLD*
欧洲
EASL**
日本
JSH***
高危人群 肝硬化
慢性乙肝
肝硬化
慢性乙肝
慢性丙肝
伴随晚期肝纤维化
肝硬化
慢性乙肝
慢性丙肝
监测 美国
AASLD*
欧洲
EASL**
日本
JSH***
间隔时长 6个月 6个月
风险较高时6个月
风险极高时3-4个月
监测项目 超声
(选择性监测AFP)
超声
(证据不足时,监测AFP,AFP-L3,PIVKAII)
超声
AFP,AFP-L3,PIVKA II

* 美国肝病研究学会,American Association for the Study of Liver Diseases
**欧洲肝脏研究学会,European Association for the Study of the Liver
***日本肝病学会,The Japan Society of Hepatology

HCC肿瘤标记物有助于检出早期HCC

血清学肿瘤标记物AFP-L3和PIVKA II与HCC发展相关,任一肿瘤标记物的升高都是慢性肝病患者发展为HCC的早期指标。多项研究表明,在可以通过影像学检出HCC之前,AFP-L3和PIVKAII水平就会升高。因此,将两种肿瘤标记物添加到常规定期监测项目(诸如AFP和超声),可以帮助医生在高危患者中及早识别HCC肿瘤。

在可以通过影像学方法检出之前,AFP-L3和PIVKAII可以提示HCC的早期发展,并且可用于识别HCC风险增加的患者[10-12]

一项纳入438例HCC患者的研究表明,AFP-L3和PIVKAII是HCC肿瘤进展的独立标记物[13]。据报道,AFP-L3值上升预示着发展为HCC的恶性程度增大,肿瘤体积的倍增时间缩短,肝动脉供血量增大[14]。AFP-L3值也与HCC的病理特征相关,如浸润性肿瘤生长模式,包膜浸润和血管侵袭[15]。据报道,PIVKAII是微侵袭的特异性标记物,高PIVKA II水平与门静脉侵袭的发生有关[16,17]

AFP-L3,PIVKA II是互补的肿瘤标记物,已被证实为有效的肝癌早期诊断的肿瘤标记物[18-22]

AFP-L3和PIVKA II监测可用于体外诊断(IVD)

在全球范围内,PIVKAII和AFP-L3检测均可用于体外诊断,在美国和日本已纳入医保。如需了解更多的订购信息,请联系wako.info02@fujifilm.com

通过一台全自动电泳荧光免疫分析仪(即µTASWako i30),实验室可以在一份血清样本中检测出AFP,AFP-L3和PIVKAII[20-23]
请访问"µTASWako i30"页面了解更多信息。

References

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  2. Stravitz RT, et al. Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome. Am J Med. 2008;121:119-26.
  3. Heimbach JK, et al. AASLD Guidelines for the Treatment of Hepatocellular Carcinoma: Hepatology. 2018 Jan;67 (1):358-380
  4. EASL Clinical Practice Guideline: Management of hepatocellular carcinoma: J Hepatol. 69 (2018) 182-236
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  6. Bruix J, Sherman M. Management of Hepatocellular Carcinoma: An Update. Hepatology. 2011;53:1020-2
  7. Singal AG, et al. Effectiveness of Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis. Cancer Epidemiol Biomarkers Prev. 2012;21:793-9.
  8. Singal AG, et al. Detection of Hepatocellular Carcinoma at Advanced Stages Among Patients in the HALT-C Trial: Where Did Surveillance Fail? Am J Gastroenterol. 2013;108:425-32.
  9. Ikai I, et al. Survey Report of the 18th follow-up survey of primary liver cancer in Japan. Hepatol Res. 2010;40:1043-59.
  10. Taketa K, et al. A collaborative study for the evaluation of lectin-reactive a-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res 1993;53:5419-23.
  11. Shiraki K, et al. A clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients. Hepatology 1995;22:802-7.
  12. Oda K, et al. Highly sensitive lens culinaris agglutinin-reactive a-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease. Oncol Rep 2011;26:1227-33.
  13. Toyoda H. et al. Diagnosis Of Hepatocellular Carcinoma Using A GALAD Model By Objective Clinical And Serological Factors. The Liver Meeting 2013 Poster 2112
  14. Kumada T, et al. Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: special reference to imaging diagnosis. J Hepatol 1999;30:125-30.
  15. Tada T, et al. Relationship between Lens culinaris agglutinin-reactive alpha-fetoprotein and pathologic features of hepatocellular carcinoma. Liver Int 2005;25:848-53.
  16. Koike Y, et al. Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer 2001;91:561-9.
  17. Yamashita Y, et al. Predictors for Microinvasion of Small Hepatocellular Carcinoma =2 cm. Ann Surg Oncol. 2012;19:2027-34
  18. Shimauchi Y, et al. A simultaneous monitoring of Lens culinaris agglutinin A-reactive alpha-fetoprotein and desgamma-carboxy prothrombin as an early diagnosis of hepatocellular carcinoma in the follow-up of cirrhotic patients. Oncol Rep 2000;7:249-56.
  19. Arii S, et al. Management of hepatocellular carcinoma: Report of Consensus Meeting in the 45th Annual Meeting of the Japan Society of Hepatology (2009). Hepatol Res. 2010;40:667-85.
  20. Choi JY, et al. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol. 2013;19:339-46.
  21. Hann HW, et al. Usefulness of highly sensitive AFP-L3 and DCP in surveillance for hepatocellular carcinoma in patients with a normal alpha-fetoprotein. J Med Microb Diagn. In press 2014.
  22. Choi J, et al. Longitudinal Assessment of Three Serum Biomarkers to Detect Very Early-Stage Hepatocellular Carcinoma. Hepatology. 2018 Aug. 28
  23. Kagebayashi C, et al. Automated immunoassay system for AFP-L3% using on-chip electrokinetic reaction and separation by affinity electrophoresis. Anal Biochem. 2009;388:306-11.

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