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Hepatocellular Carcinoma

By Steven K. Herrine, MD, Thomas Jefferson University;Sidney Kimmel Medical College

Hepatocellular carcinoma (hepatoma) is a cancer that begins in the liver cells.

  • Having hepatitis B or hepatitis C or drinking excess alcohol increases the risk of developing hepatocellular carcinoma, especially in people with cirrhosis of the liver.

  • People may have abdominal pain, lose weight, and feel a large mass in the upper right part of the abdomen.

  • Doctors base the diagnosis on results of a blood test and imaging tests.

  • This cancer is usually fatal unless it is diagnosed early.

Hepatocellular carcinoma is the most common type of cancer originating in the liver. It usually occurs in people who have severe scarring of the liver (cirrhosis—see Cirrhosis of the Liver).

In certain areas of Africa and East Asia, hepatocellular carcinoma is more common than it is the United States and is a common cause of death. In these areas, many people have chronic infection with the hepatitis B virus. The presence of this virus in the body increases the risk of hepatocellular carcinoma more than 100-fold. Hepatitis B can cause cirrhosis, but it can lead to hepatocellular carcinoma whether cirrhosis develops or not. Cirrhosis due to chronic hepatitis C or excessive alcohol use also increases the risk of this cancer.

Having hemochromatosis (a hereditary disorder that causes the body to absorb too much iron—see Hemochromatosis) also increases the risk of developing hepatocellular cancer. Iron may accumulate in the liver and damage it.

Hepatocellular carcinoma sometimes results from exposure to certain cancer-causing substances (carcinogens). In subtropical regions where hepatocellular carcinoma is common, food is often contaminated by carcinogens called aflatoxins, substances that are produced by certain types of fungi.

In North America, Europe, and other geographic areas where hepatocellular carcinoma is less common, the most common cause is chronic hepatitis C. Cirrhosis, most commonly long-standing cirrhosis related to chronic hepatitis C or chronic alcohol use, can also lead to hepatocellular carcinoma. The risk is lower with primary biliary cirrhosis than with other types of cirrhosis.

Symptoms

Usually, the first symptoms are abdominal pain, weight loss, and a large mass that can be felt in the upper right part of the abdomen. People who have had cirrhosis for a long time may unexpectedly become much more ill. A fever may occur. Occasionally, the first symptoms are sudden abdominal pain and shock (dangerously low blood pressure) caused by rupture or bleeding of the cancer.

Occasionally, hepatocellular carcinoma interferes with how the body processes certain substances (metabolism). For example, this cancer can lead to low sugar levels (hypoglycemia), high calcium levels (hypercalcemia), and high fat levels (hyperlipidemia) in the blood.

Diagnosis

Detecting hepatocellular carcinoma early is difficult because at first, the symptoms do not provide many clues. If a doctor feels an enlarged liver or if an imaging test detects a mass in the upper right part of the abdomen during an examination done for other purposes, the doctor may suspect this cancer, especially in people with long-standing cirrhosis. However, screening programs often enable doctors to detect this cancer before symptoms develop.

If hepatocellular carcinoma is suspected, the following are done:

  • Blood tests to measure levels of alpha-fetoprotein: This protein is normally produced by the fetus, and levels decrease markedly by age 1 year. Levels are high in about half the people with hepatocellular carcinoma.

  • Physical examination: Doctors feel the upper right part of the abdomen to check for an enlarged liver or mass. They may place a stethoscope over the liver to check for sounds caused by the cancer. For example, they occasionally hear rushing sounds (hepatic bruits, which are due to blood rushing through blood vessels inside the cancer) or scratchy sounds (friction rubs, which are due to the cancer rubbing against the liver surface and surrounding structures).

  • Imaging tests: Doctors may use ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI) of the abdomen to check for hepatocellular carcinoma. CT and MRI tend to be more accurate than ultrasonography. Before CT or MRI is done, a dye is injected into a vein. The dye helps make abnormalities, if present, easier to see.

If the diagnosis is still unclear, a liver biopsy (removal of a small sample of liver tissue with a needle for examination under a microscope) can confirm the diagnosis (see Biopsy of the Liver). To improve the chances of obtaining cancerous tissue, doctors often use ultrasonography or CT to guide the placement of the biopsy needle. The risk of bleeding or other injury during a liver biopsy is usually low.

Staging

If cancer is diagnosed, doctors determine how large the cancer is and whether it has spread to nearby structures or other parts of the body. The imaging tests used for diagnosis can provide some of this information.

The cancer is classified ranging from stage I (a single tumor that has not spread) to stage IV (spread to distant parts of the body). Staging helps doctors decide on treatment and estimate survival.

Screening

In some areas where the hepatitis B virus is common, ultrasonography is used to screen people with hepatitis B for liver cancer. Some doctors periodically screen people with cirrhosis, regardless of cause. Screening usually involves measurement of the alpha-fetoprotein level and ultrasonography every 6 or 12 months.

Prognosis

Most people with hepatocellular carcinoma do not live for more than a few years because the cancer is detected at a late stage. Screening and early detection result in a better prognosis. If the cancer is small and has not spread and liver transplantation can be done, the person can often live a number of years.

Prevention

Use of the vaccine against hepatitis B virus (see Hepatitis B Vaccine) eventually reduces the incidence of hepatocellular carcinoma, especially in areas where the virus is common. Preventing the development of cirrhosis regardless of cause can also help. For example, treating chronic hepatitis C or hemochromatosis and treating or preventing alcohol-related liver disease can help prevent the cancer from developing.

Treatment

Only liver transplantation or surgical removal of the cancer offers any hope of cure. However, when the cancer is surgically removed, it often recurs. Also, removing the cancer in people who have cirrhosis may not be possible because too much of their liver is damaged.

When transplantation or surgery is not possible or when people are waiting for a liver transplant, treatments that focus on the tumor and areas around it can be used. These treatments may help slow the cancer's growth and relieve symptoms. For example, doctors may inject a chemical that destroys cancer cells into blood vessels to the cancer. Or they may use treatments that apply energy to cancer cells and thus destroy them. Three such treatments are

  • Radiofrequency ablation (which uses electrical energy)

  • Cryoablation (which uses cold)

  • Selective internal radiation therapy (which uses radiation)

However, these treatments do not destroy all the cancer cells. Radiation therapy applied to the outside of the body is usually ineffective.

Chemotherapy drugs can be injected into a vein or into the hepatic artery. Injecting chemotherapy drugs directly into the hepatic artery delivers a large amount of the drugs directly to the cancer cells in the liver. The chemotherapy drug sorafenib is effective against hepatocellular carcinoma. Other chemotherapy drugs are being studied as treatments for this cancer.

Drugs Mentioned In This Article

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  • NEXAVAR

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