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Risk assessment of patients with chronic liver disease for development of hepatocellular carcinoma (HCC)
An aid in the monitoring of HCC patients post therapy if des-gamma-carboxy prothrombin (DCP) level was elevated prior to therapy. An elevated DCP level is associated with increased risk of recurring HCC.
Des-gamma-carboxy prothrombin (DCP), also known as the protein induced by vitamin K absence or antagonist II (PIVKA-II), is an abnormal form of the coagulation protein, prothrombin. DCP is a nonfunctional prothrombin resulting from a lack of carboxylation of 10 glutamic acid residues in the N-terminal portion of the molecule. In normal liver, prothrombin undergoes post-translational carboxylation before release into the peripheral blood. The carboxylation converts specific amino-terminal glutamic acid residues to gamma-carboxyglutamic acid. The vitamin K dependent carboxylase responsible for the carboxylation is absent in many hepatocellular carcinoma (HCC) cells, and an abnormal prothrombin with all or some of unconverted glutamic acid is secreted. Therefore, this noncarboxylated form (DCP) has been used as an HCC biomarker.
DCP is considered a complementary biomarker to alpha fetoprotein (AFP) and third electrophoretic form of lentil lectin-reactive AFP% (AFP-L3%) for assessing the risk of developing HCC. The elevation of both AFP-L3 and DCP indicate progression of HCC, albeit they reflect different features of the progression. In a prospective study of patients in the United States with an established diagnosis of HCC, the sensitivities for AFP, AFP-L3%, and DCP were 68%, 62%, and 73%, respectively. When the 3 markers were combined, the sensitivity was 86%. In another study, DCP levels were shown to correlate with tumor size and metastatic HCC. In this study, compared to AFP and AFP-L3%, DCP had the highest sensitivity (87%) and the highest positive predictive value (87%) in patients with HCC due to chronic hepatitis B and C infections. A number of studies have shown that elevated serum DCP is significantly related to portal vein invasion and/or intrahepatic metastasis, which significantly affect prognosis for patients with HCC.
DCP can be elevated in other conditions besides HCC. Conditions such as obstructive jaundice, intrahepatic cholestasis causing chronic decrease in vitamin K, and ingestion of drugs such as warfarin or wide-spectrum antibiotics can result in high concentrations of DCP. In addition, 25% to 50% of patients with HCC will have a DCP value within the reference range. Because of this, a normal DCP value does not rule out HCC.
In patients with an elevated des-gamma-carboxy prothrombin (DCP) result (> or =7.5 ng/mL), the risk of developing hepatocellular carcinoma (HCC) is 36.5% (95% CI 23.5%-49.6%). The risk of developing HCC with a negative DCP result (<7.5 ng/mL) is 7.6% (95% CI 4.4%-10.8%).
Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedures, may have circulating anti-animal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results.
Serum markers are not specific for malignancy, and values may vary by method. Do not interpret des-gamma-carboxy prothrombin (DCP) levels as absolute evidence of the presence or absence of malignant disease. Results should be used in conjunction with information from the clinical evaluation of the patient, cytology, and imaging procedures.
DCP producing tumors other than hepatocellular carcinoma can show elevated DCP values.
Liver disease caused by other etiologies such as alcohol liver disease, hematochromatosis, Wilson disease, autoimmune hepatitis, and steatohepatitis have not been studied with this assay.
Medication containing vitamin K preparations may cause a negative bias with DCP values.
Medication containing vitamin K antagonist or antibiotic may cause a positive bias with DCP values.
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