How is liver cancer diagnosed?

Blood tests

Liver cancer is not diagnosed by routine blood tests, including a standard panel of liver tests. This is why the diagnosis of liver cancer depends so much on the vigilance of the physician screening with a tumor marker (alpha-fetoprotein) in the blood and radiological imaging studies.

Since most patients with liver cancer have associated liver disease (cirrhosis), their liver blood tests may not be normal to begin with. If these blood tests become abnormal or worsen due to liver cancer, this usually signifies extensive cancerous involvement of the liver. At that time, any medical or surgical treatment may be too late.

Sometimes, however, other abnormal blood tests can indicate the presence of liver cancer. Remember that each cell type in the body contains the full complement of genetic information. What differentiates one cell type from another is the particular set of genes that are turned on or off in that cell. When cells become cancerous, certain of the cell's genes that were turned off may become turned on. Thus, in liver cancer, the cancerous liver cells may take on the characteristics of other types of cells. For example, liver cancer cells sometimes can produce hormones that are ordinarily produced in other body systems. These hormones then can cause certain abnormal blood tests, such as a high red blood count (erythrocytosis), low blood sugar (hypoglycemia) and high blood calcium (hypercalcemia).

Another abnormal blood test, high serumcholesterol (hypercholesterolemia), is seen in up to 10% of patients from Africa with liver cancer. The high cholesterol occurs because the liver cancer cells are not able to turn off (inhibit) their production of cholesterol. (Normal cells are able to turn off their production of cholesterol.)

There is no reliable or accurate screening blood test for liver cancer. The most widely used biochemical blood test isalpha-fetoprotein (AFP), which is a protein normally made by the immature liver cells in the fetus. At birth, infants have relatively high levels of AFP, which fall to normal adult levels by the first year of life. Also, pregnant women carrying babies with neural tube defects may have high levels of AFP. (A neural tube defect is an abnormal fetal brain or spinal cord that is caused by folic acid deficiency during pregnancy.)

In adults, high blood levels (over 500 nanograms/milliliter) of AFP are seen in only three situations:

• Liver cancer
• Germ cell tumors (cancer of the testes and ovaries)
• Metastatic cancer in the liver (originating in other organs)

Several assays (tests) for measuring AFP are available. Generally, normal levels of AFP are below 10 ng/ml. Moderate levels of AFP (even almost up to 500 ng/ml) can be seen in patients with chronic hepatitis. Moreover, many patients with various types of acute and chronic liver diseases without documentable liver cancer can have mild or even moderate elevations of AFP.

The sensitivity of AFP for liver cancer is about 60%. In other words, an elevated AFP blood test is seen in about 60% of liver cancer patients. That leaves 40% of patients with liver cancer who have normal AFP levels. Therefore, a normal AFP does not exclude liver cancer. Also, as noted above, an abnormal AFP does not mean that a patient has liver cancer. It is important to note, however, that patients with cirrhosis and an abnormal AFP, despite having no documentable liver cancer, still are at very high risk of developing liver cancer. Thus, any patient with cirrhosis and an elevated AFP, particularly with steadily rising blood levels, will either most likely develop liver cancer or actually already have an undiscovered liver cancer.

An AFP greater than 500 ng/ml is very suggestive of liver cancer. In fact, the blood level of AFP loosely relates to (correlates with) the aggressiveness of the liver cancer. Finally, in patients with liver cancer and abnormal AFP levels, the AFP may be used as a marker of response to treatment. For example, an elevated AFP is expected to fall to normal in a patient whose liver cancer is successfully removed surgically (resected). People with higher AFP levels generally do not live as long as those with lower AFP levels.

There are a number of other liver cancer tumor markers that currently are research tools and not generally available. These include des-gamma-carboxyprothrombin (DCP), a variant of the gamma-glutamyltransferase enzymes, and variants of other enzymes (for example, alpha-L-fucosidase), which are produced by normal liver cells. (Enzymes are proteins that speed up biochemical reactions.) Potentially, these blood tests, used in conjunction with AFP, could be very helpful in diagnosing more cases of liver cancer than with AFP alone.

Reviewed by Melissa Conrad Stöppler, MD on 9/16/2011

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