Des-gamma carboxyprothrombin

Des-gamma carboxyprothrombin (DCP), also known as protein induced by vitamin K absence or antagonist-II (PIVKA-II), is an abnormal form of the coagulation protein, prothrombin. Normally, the prothrombin precursor undergoes post-translational carboxylation by gamma-glutamyl carboxylase in the liver prior to secretion into plasma. Many hepatocellular carcinoma (HCC) cells however, lack the carboxylation activity and secrete unmodified prothrombin precursor DCP. DCP lacks thrombotic activity and many clinical research papers have shown that DCP is present in the sera of HCC patients [1-5].

In 1984, Liebman et al. found DCP in high prevalence with high specificity in sera of patients with HCC, and proposed it as a novel serum marker of HCC [6]. Many clinical studies have since shown that DCP is significantly elevated in HCC patients and that DCP was able to discriminate HCC from nonmalignant hepatopathy (i.e. chronic hepatitis B & hepatitis C and liver cirrhosis) with high specificity [2-5]. DCP level has also been demonstrated to be significantly associated with metastasis of tumor and the development of portal vein invasion (PVI) [7].

Though DCP has been used extensively in Japan for many years for HCC management, its clinical utility was only recently evaluated in the United States. Recent US studies reported that DCP is indeed effective in discriminating HCC from non-malignant hepatopathy for the North American demographic. A recently published case-controlled study reported that, DCP was able to differentiate early stage HCC from cirrhosis with high accuracy (at 150 mAU/mL): 92% sensitivity and 93% specificity. In addition, DCP identified 15 (88%) of 17 patients with early stage HCC that would have been missed utilizing the traditional HCC marker AFP alone during screening [4].

The target population to be screened for DCP is similar to that of another HCC marker, Lens culinaris reactive AFP (AFP-L3): patients with chronic hepatitis (CH), and cirrhosis. However, DCP is independently expressed. DCP therefore, is regarded as an independent and complimentary HCC marker for risk assessment, surveillance and detection of HCC [8-10].