What’s New and Emerging?
Measurement of Des-Gamma Carboxy Prothrombin: One of the normal functions of the liver is to synthesize and secrete proteins that aid in normal blood clotting. One important protein of this kind is called prothrombin. It is also known as Factor 2 in the cascade of blood coagulation. Prothrombin, like several other clotting factors (factors 7, 9 and 10), contain amino acid residues that normally are carboxylated by enzyme mechanisms that depend upon the presence of adequate amounts of normal functioning Vitamin K. Such factors are also called "Vitamin K-dependent clotting factors."
Several years ago, Japanese investigators discovered that many patients with hepatocellular carcinoma produce an abnormal type of prothrombin, a type that is deficient in carboxylation. This discovery has led to development of several generations of a serum test to detect such abnormal forms of prothrombin. Comparison of results of this test with serum alfa-fetoprotein has shown that both tests are of similar sensitivity and specificity for HCC, but that the two, used together, at least in Japanese patients, significantly improves the detection of early HCC. It remains to be seen whether similar results will be achievable for patients with HCC in the USA or other regions. If such studies corroborate the findings from Japan, measurement of des-gamma carboxy prothrombin in serum will become a new standard method for screening for HCC.
Improvements in Hepatic Ultrasound: New methods are being developed that allow for blood flow to be monitored by ultrasonography in hepatic lesions, such as regenerative nodules or small HCC's. According to recent work, again from Japan, where HCC is much more prevalent than in the USA, performance of hepatic ultrasound with such dynamic flow markers has improved sensitivity and specificity for diagnosis of HCC.
Advances in Other Imaging Modalities: In view of the rapid progress made in CT scanning and MRI scanning, there is little reason to doubt that additional advances in these modalities of hepatic imaging will also continue.
Serum Genetic Markers of Hepatocytic Dysplasia and/or HCC: As described elsewhere, the development of abnormal liver cells, some of which may become cancerous, is associated with (and probably requires) genetic changes in DNA of hepatocytes. Some of these cancerous cells probably find their ways every day into the blood stream from the site of the primary cancer. Extremely sensitive methods for detecting mutations are becoming available. These generally are dependent upon the polymerase chain reaction (PCR), which can carry out logarithmic amplification of cancer-associated gene fragments, and new and highly sensitive cytometric analyses of cancerous or dysplastic cells. These technologies are in their infancy and advances are likely to be rapid. However, careful studies will still need to be done to insure the reliability, sensitivity, and specificity of abnormal results. Such careful studies are likely to take several years.
The Future of Screening for HCC
- Measurement of des-gamma carboxy prothrombin in serum.
- Dynamic flow markers with hepatic ultrasounds.
- Serum genetic markers of hepatocytic dysplasia and/or HCC (finding the needle in the haystack): PCR-based amplification of cancer-associated genes; Flow cytometric analyses of cancerous cells
