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Liver Cancer

The Merck Manual Home Edition
"Primary liver cancers are cancers that originate in the liver. The most common is hepatocellular carcinoma (hepatoma). At first, liver cancer usually causes only vague symptoms (such as weight loss, loss of appetite, and fatigue). As a result, the diagnosis is often made late, and the prognosis is usually poor.

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.
*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).

In certain areas of Africa and East Asia, hepatocellular carcinoma is more common than metastatic liver cancer 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.

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 alcohol use, can also lead to hepatocellular carcinoma. The risk is lower with primary biliary cirrhosis than with other types of cirrhosis.

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.

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 a 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. The risk of bleeding or other injury during a liver biopsy is usually low.

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.

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.

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.

Use of the vaccine against hepatitis B virus 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 and treating or preventing alcohol-related liver disease can help prevent the cancer from developing.

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), and 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.

Other primary liver cancers are uncommon or rare. For diagnosis, a biopsy is usually needed. Most people with these cancers have a poor prognosis. If the cancer has not spread, it can sometimes be removed. When it can be removed, people may live several years or longer.

A cholangiocarcinoma is a relatively slow-growing cancer that originates in the lining of the bile ducts in or outside the liver. In China, infestation with liver flukes (a parasite) contributes to the development of this cancer. People with primary sclerosing cholangitis are at risk of developing cholangiocarcinoma. Symptoms of the cancer are often vague but may include sudden deterioration of the person's general health, a mass in the upper right part of the abdomen, jaundice (a yellowish discoloration of the skin and the whites of the eyes), weight loss, and abdominal discomfort.

A fibrolamellar carcinoma is a rare type of hepatocellular carcinoma that usually affects relatively young adults. It is not caused by preexisting cirrhosis or hepatitis B or C and has no other known risk factors. People with fibrolamellar carcinoma usually fare better than those with other types of hepatocellular carcinoma. Many live several years after this cancer is removed.

A hepatoblastoma is a relatively common cancer in infants. Occasionally, it occurs in older children and may produce hormones (called gonadotropins) that result in early (precocious) puberty (see see Early Puberty). No cause has been identified. Health may generally deteriorate, and a mass may be felt in the upper right part of the abdomen.

An angiosarcoma is a rare cancer originating in the blood vessels of the liver. An angiosarcoma may be caused by exposure to vinyl chloride in the workplace, as occurs in the manufacture of polyvinyl chloride (PVC), or by exposure to arsenic. However, in most people, no cause is identified.

Diagnosis and Treatment:
A hepatoblastoma is usually suspected when doctors feel a large mass in the upper right part of an infant's abdomen and the infant's health is deteriorating. Results of blood tests to measure levels of alpha-fetoprotein levels and imaging tests may help doctors make the diagnosis.

Cholangiocarcinoma in the liver, hepatoblastoma, and angiosarcoma are diagnosed by liver biopsy (removal of a sample of liver tissue with a needle for examination under a microscope—Biopsy).

Cholangiocarcinoma of the bile ducts outside the liver is usually diagnosed using special x-ray techniques (such as endoscopic retrograde cholangiopancreatography [ERCP] or percutaneous transhepatic cholangiography) or surgery. In two thirds of people with this type of cancer, the cancer has already spread to nearby lymph nodes by the time it is detected.

Usually, treatment of these cancers has little effect, and most people die within a few months of when the cancer was detected. However, if the cancer is detected relatively early, it may be surgically removed, offering the hope of long-term survival."

Medications Used in Treatment:
1. Kinase Inhibitors: Nexavar®/sorafenib

Suggested Links:
*N.H.S. Choices (with Video)
*Medscape/ Hepatocellular Cancer
*International Liver Cancer Association

*[Editor] Japan experienced infection of a large part of their population after WWII due to the post-transfusion infections with hepatitis B and C. Twenty years later they experienced a wave of related liver cancer. The United States is at that same point; 20 years after the wide-spread infection of hepatitis from drug use.

*[Editor] Nexavar is the most expensive the the kinase inhibitors. It is the drug therapy most mentioned, but the cost drops dramatically outside the United States.

*[Editor] Of strong interest to the Editor is the fact that advanced hepatocellular carcinoma (HCC) expresses sex hormone receptors and HBV related cancer appear more frquenctly in men and post-menopausal women. Trials with Taxomifen and Megace have failedto be overwhelmingly successful; but no one yet has incorporated our unique stanozolol/ nandrolone therapy i a population limited to women. As these drugs may be used in a 'compassionate' setting, we welcome contract from physicians for their terminally-ill individuals. The author will supply treatment at no out-of-pocket cost.

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