Methods for Screening for HCC
Alpha-fetoprotein (AFP): The alpha-fetoprotein or alfafetuin is the major protein made by the liver found in the circulation of fetuses. Late in gestation, the synthesis of AFP falls, while the synthesis of human serum albumin increases by liver cells. Albumin is the major serum protein found in humans after birth.
The development of HCC, similar to the development of tumors in other organs, often leads to a "dedifferentiation" of the appearance and function of the cells of origin of the cancer. In the case of HCC, the cells of origin are the hepatocytes or parenchymal cells of the liver. It has been known for at least a generation that levels of AFP in serum often increase as hepatocytes undergo dedifferentiation, development of dysplasia, anaplasia, and eventually frank neoplasia (cancer).
Elevations in AFP and serum can be measured simply and inexpensively, and this has been the cornerstone of screening methods. However, some HCC's do not over- produce AFP. Only about two thirds of patients with documented HCC's have elevations in serum AFP. Then, too, elevations of serum AFP may occur in liver disorders other than HCC or in cancers other than HCC. Many kinds of acute and chronic hepatitis are associated with elevations in AFP levels, although these are generally relatively mild and not greater than 200 nanograms per mL of serum. In general, any pertubation or stimulus that leads to increased growth or division of liver cells may be associated with elevations of serum AFP levels.
Ultrasound: The imaging studies that are useful are those that allow us to detect heterogeneities within the liver. Currently, this is done chiefly with hepatic ultrasound, CT scanning, or magnetic resonance imaging (MRI). Ultrasound examinations are the least expensive and do not involve any known risks to the patient (no exposure to ionizing radiation, nor to high magnetic fields). However, hepatic ultrasound is highly dependent upon the experience and level of interest of the ultrasonographer. Therefore, results are more variable with this modality than with other imaging modalities. In certain patients, such as those who are obese or who have much air within abdominal hollow organs or in lung overlying the liver, it is difficult to obtain hepatic ultrasonography of high quality.
Computed Tomographic (CT) Scanning: CT scans are now widely available, they do involve some exposure to ionizing (x-ray) radiation, but these are relatively low. The sensitivity and specificity of hepatic CT scanning can be improved by doing rapid scans after the injection of iodinated contrast material into blood vessel (a technique called 3 phase helical CT scanning). Multi-phase helical scans are now considered the standard for CT scanning of the liver, and they can show up small masses that were missed on non-contrast or regular contrast CT scans or ultrasound examinations of the liver.
Magnetic Resonance Imaging (MRI): MRI is increasingly available, particularly in the USA and other developed countries. It requires expensive instrumentation, including a powerful magnet into which patients are placed on a stretcher. The experience is like being in a confined tunnel sort of space, and there are some fairly loud banging noises produced by the magnet during the procedure. Some patients with claustrophobia or other severe anxiety states find themselves unable to tolerate MRI. More "open"-type MRI scanners are becoming available gradually. Patients that have paramagnetic metals in their bodies may not undergo MRI scans. This includes patients with a history of trauma to the eyes if from metallic fragments or other sources of potential paramagnetic metals. Techniques with MRI continue to improve, as do contrast materials that can be injected into blood vessels prior to or during MRI scanning. Such techniques can increase sensitivity and specificity of the method.
Lipiodol-Assisted CT Scanning of the Liver: Lipiodol is an iodinated lipid-soluble material that can be injected into blood vessels of patients. It tends to be taken up and stored selectively in liver cancers or precancerous regenerative nodules. Use of this agent has been found to increase the sensitivity of CT scanning for HCC. However, not all of the nodules or tumors that take up and store lipiodol are necessarily hepatocellular carcinomas. Nevertheless, it is generally assumed that cells in the liver that store lipiodol more avidly than other, more nearly normal, cells or regions of the liver, are cells at high risk to dedifferentiate further into HCC, if they are not already at this point.
Because, as noted above, there is no "perfect" screening test, the most sensible procedure currently is to combine several methods. For example, one might do 3-phase CT scanning of the liver in January, serum alpha-fetoprotein measurement in May, and abdominal ultrasound with special attention to the liver in September of each year.
We recommend to our patients and referring physicians that some screening tests should be done in patients at high risk at least once every 6 months. In some centers, ultrasounds are performed as often as once every three months.
Suggested Method for Screening for HCC
- Perform a screening test at least once every 6 months.
- Use different methods, as they are complementary and none is perfect or ideal.
- Specific method(s) used may vary, depending upon local interest and expertise.
- At least once each year, perform: serum alpha-fetoprotein*, liver ultrasound*, four-phase CT imaging of the liver*
*We recommend that one of these be performed every four months.
The specific methods used will vary from center to center, depending upon the local interest and expertise of specialists in imaging techniques and availability of instruments. In some parts of the world (e.g., Japan and Germany along with some other western European countries), hepatic ultrasounds are carried out by hepatologists or even by general gastroenterologists. This is not the usual pattern of practice that has evolved in the USA, where most hepatic imaging, including hepatic ultrasound, is carried out by specialists in radiology and/or their technicians or other personnel.
