异常凝血酶原（PIVKA-II）与甲胎蛋白（AFP）广泛应用于肝细胞肝癌（HCC）的诊断，而且已经被写入多个国家的原发性肝癌诊疗指南中。在临床应用当中，甲胎蛋白(AFP)是目前应用最广泛的HCC监测和诊断生物标志物，但其性能不尽人意，AFP诊断HCC的敏感度只有40-60%，而在早期HCC中敏感度则更低，只有10-20%。一方面，AFP并不是在所有形式的HCC中都有表达;另一方面，在HCC以外的慢性肝病患者中也可以发现AFP升高。由于AFP检测小肝癌(通常定义为肿瘤直径小于3cm)的敏感性和特异性较低，美国肝病研究协会(AASLD)建议仅使用超声(不含AFP)监测HCC。

PIVKA-II是一种凝血酶原，在肝细胞合成过程中不使用维生素K，导致合成不足。当由于癌细胞合成凝血酶原前体异常而发生HCC时，凝血酶原前体羧化不足，导致大量PIVKA-II产生。PIVKA-II是一种新发现的诊断HCC的肿瘤标志物，其诊断价值高于AFP。有一些研究显示PIVKA-II对HCC诊断的敏感性在90%以上，而对早期HBV相关HCC的检测敏感性在50%以上。当PIVKA-II和AFP联合用于HCC及早期HCC诊断时，其诊断价值较单个蛋白的检测明显提高。

之前有两篇系统综述评估了PIVKA-II和/或AFP诊断HCC的准确性。Tateishi等人评估了AFP或PIVKA-II对HCC诊断准确性的项研究，结果表明PIVKA-II比AFP更能检测HCC。Li等人对PIVKA-II/AFP联合和单独各标记物检测HCC的诊断准确性进行了系统综述，他们的结论是PIVKAII优于AFP，尽管PIVKA-II单独和PIVKA-II/AFP联合没有显著差异。而在2018年的一篇meta表明，无论肿瘤大小、患者种族或HCC病因，PIVKA-II在诊断HCC的准确性方面优于AFP。

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