How is liver cancer diagnosed?

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How is liver cancer diagnosed?

Blood testsLiver cancer is not diagnosed by routine blood tests, including a standardpanel of liver tests. This is why the diagnosis of liver cancer depends so much on thevigilance of the physician screening with a tumor marker (alpha-fetoprotein) inthe blood and radiological imaging studies. Since most patients with liver cancer haveassociated 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 ofliver cancer. Remember that each cell type in the body contains the full complement ofgenetic information. What differentiates one cell type from another is theparticular set of genes that are turned on or off in that cell. When cellsbecome cancerous, certain of the cell's genes that were turned off may becometurned on. Thus, in liver cancer, the cancerous liver cells may take on thecharacteristics of other types of cells. For example, liver cancer cells sometimes canproduce hormones that are ordinarily produced in other body systems. Thesehormones then can cause certain abnormal blood tests, such as a high red bloodcount (erythrocytosis), low blood sugar (hypoglycemia) and high blood calcium

Another abnormal blood test, high serum cholesterol (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) theirproduction of cholesterol. (Normal cells are able to turn off their productionof cholesterol.)

There is no reliable or accurate screening blood test for liver cancer. The mostwidely used biochemical blood test is alpha-fetoprotein (AFP), which is aprotein 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 bythe first year of life. Also, pregnant women carrying babies with neural tubedefects may have high levels of AFP. (A neural tube defect is an abnormal fetalbrain or spinal cord that is caused by folic acid deficiency during pregnancy)

In adults, high blood levels (over 500 nanograms/milliliter) of AFP are seenin 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 levelsof AFP are below 10 ng/ml. Moderate levels of AFP (even almost up to 500ng/ml) can be seen in patients with chronic hepatitis. Moreover, many patientswith various types of acute and chronic liver diseases without documentable liver cancercan have mild or even moderate elevations of AFP.

The sensitivity of AFP for liver cancer is about 60%. In other words, an elevated AFPblood test is seen in about 60% of liver cancer patients. That leaves 40% of patientswith liver cancer who have normal AFP levels. Therefore, a normal AFP does not excludeliver 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 abnormalAFP, despite having no documentable liver cancer, still are at very high risk ofdeveloping liver cancer. Thus, any patient with cirrhosis and an elevated AFP,particularly with steadily rising blood levels, will either most likely developliver 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 bloodlevel 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 ofresponse to treatment. For example, an elevated AFP is expected to fall tonormal 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 andnot generally available. These include des-gamma-carboxyprothrombin (DCP), avariant of the gamma-glutamyltransferase enzymes, and variants of other enzymes(for example, alpha-L-fucosidase), which are produced by normal liver cells. (Enzymesare proteins that speed up biochemical reactions.) Potentially, these bloodtests, used in conjunction with AFP, could be very helpful in diagnosing morecases of liver cancer than with AFP alone.