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HCC肿瘤标记物

和光肝细胞癌(HCC)肿瘤标记物AFP-L3和PIVKA II 为体外诊断产品,可以作为慢性肝病患者发展为HCC的风险评估的辅助工具。

AFP-L3: 甲胎蛋白异质体
PIVKA II: 异常凝血酶原

HCC监测改善患者预后

在全球范围内,HCC的发病率不断升高。HCC是世界癌症相关死亡的第二大病因。它是男性第五大常见癌症,女性第九大常见癌症[1]

HCC的早期监测对于有效治疗的应用和患者预后的改善至关重要。HCC监测提高了早期接受治疗的HCC患者的长期无肿瘤生存率[2]

国际肝病权威组织认可肝硬化患者和慢性乙肝/丙肝患者发展为HCC的风险非常高[2-5]。他们建议高风险患者参加HCC早期监测计划,以便及早发现HCC。

HCC监测的推荐标准

美国
AASLD*
欧洲
EASL**
日本
JSH***
间隔时长 6个月 6个月 极高风险时3-4个月,
高风险时6个月
监测项目 超声(选择性检测AFP) 超声(证据不足时,检测AFP,AFP-L3,PIVKA II) 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
请访问"肝癌监测"页面了解更多信息。

HCC肿瘤标记物的监测可以提高早期检出HCC的几率

多项研究表明,联合使用肿瘤标记物检测时,HCC肿瘤标记物的临床应用得到提高[6-9,10,11]

肿瘤标记物AFP-L3和PIVKA II具有互补性,并能有效地及早监测HCC。

日本肝病学会(JSH)建议使用超声和肿瘤标记物,包括AFP-L3,AFP和PIVKA II,用于HCC临床监测。先进的监测措施使许多患者能够接受有效性治疗,并能提高他们的长期生存率[5]

我司AFP-L3和PIVKA II 项目目前在全球均有销售,凭借其配套的全自动电泳荧光免疫分析仪(即µTASWako i30),实验室可以在同一份血清标本中检测出AFP,AFP-L3和PIVKA II[7,10-12]

HCC肿瘤标记物的可用性和纳入医保情况

美国 加拿大 欧洲 日本
AFP 不可用于HCC 可用 可用 可用
已纳入医保
AFP-L3 可用
已纳入医保
可用 可用 可用
已纳入医保
PIVKA II 可用
已纳入医保
可用 可用 可用
已纳入医保

HCC肿瘤标记物可用于预测HCC复发和预后不良

HCC是一种即使在治愈性治疗后也具有较高复发率的癌症。HCC肿瘤标记物水平较高的患者可能发展为复发性HCC[13,14]

据报道,AFP-L3和PIVKAII与HCC患者预后不良有关[13,14]。AFP-L3值升高表明肿瘤的恶性潜能增加,PIVKAII也是门静脉侵袭程度的指标[15,16]

JSH建议对于治疗后的患者,应结合超声和HCC肿瘤标记物持续对患者进行监测,以便及早发现复发性HCC[5]

AFP-L3项目-用于体外诊断(IVD)

AFP-L3是AFP的异质体,是通常由胎儿时期肝脏产生的糖蛋白。在成人中,这种蛋白的浓度升高可以提示原发性肝癌和生殖细胞肿瘤。据报道,在HCC患者中,与总AFP或其他AFP异质体相比,AFP-L3的特异性更强[17]。AFP-L3项目反映的是AFP-L3与总AFP的百分比。
请访问"AFP-L3"页面了解更多信息。

PIVKA II 项目-用于体外诊断(IVD)

PIVKA II 是凝血酶原的一种前体形式,用于提示机体中HCC细胞的存在[18],亦称为脱-γ-羧基凝血酶原(des-γ-carboxy prothrombin, DCP)。
请访问"PIVKA II"页面了解更多信息。

References

  1. World Health Organization, International Agency for Research on Cancer. GLOBOCAN 2012, Retrieved 14 Jan 2014 from http://globocan.iarc.fr
  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
  5. Kokuno N, et al. Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res. 2015 Jan; 45 (2)
  6. Ertle JM, et al. A Combination of a-Fetoprotein and Des-gamma-Carboxy Prothrombin Is Superior in Detection of Hepatocellular Carcinoma. Digestion. 2013; 87:121-31.
  7. 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.
  8. 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.
  9. 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.
  10. 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 2014; 3:1
  11. Choi J, et al. Longitudinal Assessment of Three Serum Biomarkers to Detect Very Early-Stage Hepatocellular Carcinoma. Hepatology. 2018 Aug; 28
  12. 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.
  13. Toyoda H, et al. Clinical utility of highly sensitive Lens culinaris agglutinin-reactive alpha-fetoprotein in hepatocellular carcinoma patients with alpha-fetoprotein > 20 ng/mL. Cancer 2011 May; 102 (5) 1025-31
  14. Toyoda H, et al. Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy. J Hepatol. 2012 Dec; 57(6):1251-7
  15. 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 Feb 1;91(3):561-9
  16. Yamashita Y, et al. Predictors for microinvasion of small hepatocellular carcinoma ≤ 2 cm. Ann Surg Oncol. 2012 Jun; 19(6):2027-34
  17. Sato Y, et al. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med. 1993; 328:1802-6.
  18. Liebman HA, et al. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med. 1984; 310:1427-31.

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