Des-gamma carboxyprothrombin explained

Des-gamma carboxyprothrombin (DCP), also known as protein induced by vitamin K absence/antagonist-II (PIVKA-II), is an abnormal form of the coagulation protein, prothrombin. Normally, the prothrombin precursor undergoes post-translational carboxylation (addition of a carboxylic acid group) by gamma-glutamyl carboxylase in the liver prior to secretion into plasma. DCP/PIVKA-II may be detected in people with deficiency of vitamin K (due to poor nutrition or malabsorption) and in those taking warfarin or other medication that inhibits the action of vitamin K.

Diagnostic use

Hepatocellular carcinoma

A 1984 study first described the use of DCP as a marker of hepatocellular carcinoma (HCC); it was present in 91% of HCC patients, while not being detectable in other liver diseases. The DCP level did not change with the administration of vitamin K, suggesting a defect in gamma-carboxylation activity rather than vitamin K deficiency.^[1] A number of subsequent studies have since confirmed this phenomenon.^{[2] [3] [4]}

A 2007 comparison of various HCC tumor markers found DCP the least sensitive to risk factors for HCC (such as cirrhosis), and hence the most useful in predicting HCC.^[5] It differentiates HCC from non-malignant liver diseases.^[6] Moreover, it has been demonstrated that a combined analysis of DCP and Alpha-fetoprotein (AFP) can lead to a better prediction in early stages of HCC.^[7]

Despite many years of use in Japan, only did a 2003 American study reevaluate its use in an American patient series. It also identified HCC at an earlier stage.^[4]

Anticoagulant intoxication

A 1987 report described the use of DCP determination in the detection of intoxication with acenocoumarol, a vitamin K antagonist.^[8]

References

1. Liebman HA, Furie BC, Tong MJ . Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma . N. Engl. J. Med. . 310 . 22 . 1427–31 . 1984 . 6201741 . 10.1056/NEJM198405313102204. etal.
2. Tsai SL, Huang GT, Yang PM, Sheu JC, Sung JL, Chen DS . Ding-Shinn Chen . Plasma des-gamma-carboxyprothrombin in the early stage of hepatocellular carcinoma . Hepatology . 11 . 3 . 481–8 . 1990 . 2155866 . 10.1002/hep.1840110321.
3. Cui R, Wang B, Ding H, Shen H, Li Y, Chen X . Usefulness of determining a protein induced by vitamin K absence in detection of hepatocellular carcinoma . Chin. Med. J. . 115 . 1 . 42–5 . 2002 . 11930656 .
4. Marrero JA, Su GL, Wei W . Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in American patients . Hepatology . 37 . 5 . 1114–21 . 2003 . 12717392 . 10.1053/jhep.2003.50195. etal. free .
5. Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA . Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3 . Cancer Biomark . 3 . 2 . 79–87 . 2007 . 10.3233/cbm-2007-3202 . 17522429 .
6. Lamerz R, Runge M, Stieber P, Meissner E . Use of serum PIVKA-II (DCP) determination for differentiation between benign and malignant liver diseases . Anticancer Res. . 19 . 4A . 2489–93 . 1999 . 10470180 .
7. Ertle. JM. Heider. D. Wichert. M. Keller. B. Kueper. R. Hilgard. P. Gerken. G. Schlaak. JF. A combination of α-fetoprotein and des-γ-carboxy prothrombin is superior in detection of hepatocellular carcinoma.. Digestion. 2013. 87. 2. 121–31. 23406785. 10.1159/000346080.
8. Lefrere JJ, Gozin D . Use of des-gamma-carboxyprothrombin in retrospective diagnosis of hidden intoxication of anticoagulants . J. Clin. Pathol. . 40 . 5 . 589 . 1987 . 3584512 . 10.1136/jcp.40.5.589-b . 1141034.