Liver Cancers – Causes, Signs and symptoms

Liver Cancers

Also called: Hepatocellular Cancer, Hepatoma, Primary Liver Cancers, Hepatocellular Carcinoma

Reviewed By:
Martin E. Liebling, M.D., FACP

Summary

Liver cancer is the growth of malignant cells in the liver, the largest internal organ in the body. Although primary liver cancer is one of the most common cancers worldwide, it is much less common in the United States. Liver cancer is often a complication of liver diseases such as hepatitis or cirrhosis.

The liver is a large, complex organ with a number of vital functions, including bile production and removing alcohol and toxins from the blood. The liver is a common site for cancer metastasis, which is cancer that has spread from its area of origin (e.g., breast cancer, lung cancer). There are several types of primary liver cancer, which originate in the liver and are much less common than metastatic, or secondary, liver cancer.

Liver cancers are seldom diagnosed early because they may have no symptoms. Possible indicators include weight loss, lack of appetite, jaundice and abdominal pain or swelling. A physician may use a number of diagnostic tests to confirm liver cancer, including ultrasound, blood tests, CAT scan, MRI and biopsy.

If the cancer is confined to one part of the liver and is detected early, it may be curable by surgery. Other possible treatments include radiation, chemotherapy and ablation, a procedure that involves the use of locally applied alcohol, radio waves or cold to destroy tumors. In some cases, a liver transplant may be necessary. Treatment for the disease varies depending on the type and severity of the cancer.

Less than 10 percent of Americans with liver cancer live five years or more after diagnosis, according to the American Cancer Society. This survival rate has doubled in recent decades, and researchers hope to increase it further through improved methods of diagnosis, treatment and prevention. Children rarely get liver cancers, and most who do develop a form of the disease that is highly curable.

There are several ways to help prevent liver cancer. These involve measures to control risk factors such hepatitis, alcoholism and exposure to certain chemicals.

About liver cancers

Liver cancer is growth of malignant cells in the liver. The liver is the body’s largest internal organ. Weighing about 3 pounds (1.5 kilograms) in an adult, the liver lies behind the ribs just below the right lung and diaphragm. The liver performs numerous vital functions such as processing and storing nutrients, releasing bile into the small intestine, producing clotting factors to prevent excessive bleeding and helping remove wastes from the body. People cannot live without their livers.

Cancer develops because of damage to DNA, the genetic code found in every cell. The body is usually able to repair damage to DNA. In cancer cells, however, the DNA is not repaired and the abnormal cells become malignant and reproduce.

Scientists do not know exactly why liver cells become malignant but they do know that there is a much higher risk of cancer in people with damaged livers. Much liver damage can be attributed to conditions such as hepatitis B and hepatitis C infections. These diseases and others also produce, cirrhosis, which is severe scarring of the liver tissue. Cirrhosis by itself is a serious condition that can be fatal. When combined with liver cancer, it worsens the patient’s prognosis.

The liver can be the site of primary or secondary cancers. Secondary cancers have spread (metastasized) to the liver from another origin site, such as the breast, colon or lungs. These spreading cancers are much more common in the liver than primary liver cancer, which originates in the organ. Primary liver cancers are difficult to treat because they seldom are diagnosed early. The cancer often affects many parts of the liver or spreads to other structures. Generally, a cure is possible only when the tumor is confined to a small part of the liver. Liver cancer can be completely removed in less than 30 percent of patients undergoing exploratory surgery, according to the National Cancer Institute (NCI).

Liver cancer is one of the most common cancers worldwide. It is much less common in the United States. The number of cases increased for some years in the United States, but most recently the numbers have been decreasing. A major reason for the years of increase is the spread of hepatitis B and C, major risk factors for liver cancer.

Less than 10 percent of Americans with liver cancer live five years or more, according to the American Cancer Society (ACS). This survival rate has increased since the mid-1970s, and researchers hope to improve it further. Many patients with primary liver cancer also have cirrhosis.

Liver cancers affect men more often than women. The ACS estimates that liver cancers will be diagnosed in 13,650 American men and 5,510 American women in 2007. The ACS ranks liver cancer among the top 20 most common cancers in the United States. However, the World Health Organization ranks liver cancer in the top 5 and as the world’s third deadliest type of cancer. In some parts of Africa and East Asia, liver cancer is the most common type of cancer.

Liver cancers are rare in children, but the incidence appears to have grown in recent decades, according to the National Cancer Institute (NCI). This trend may be due to the higher survival rates of premature babies prone to hepatoblastoma and to the increase in hepatitis passed from mother to infant. In developed nations, most children with liver cancer are cured.

Types and differences of liver cancers

Liver cancers can be primary, meaning they originate in the liver, or secondary, which means the cancer has spread (metastasized) there from other areas of the body. Primary liver cancer (also called hepatic cancer and hepatoma) is more common in developing nations, whereas secondary liver cancer is more common in developed areas such as the United States and Europe.

There are several types of primary liver cancer:

  • Hepatocellular cancer (HCC, also called hepatocellular carcinoma and hepatoma). Cancer that originates in the hepatocytes, the main kind of liver cell. It accounts for 75 percent of primary liver cancers. It is not common in the United States, but its incidence is growing, primarily because of the spread of hepatitis C. HCC comes in several growth patterns:

    • Spreading. Tentacle-like tumors spread throughout the liver. It is the most common variety of HCC in the United States and usually accompanies cirrhosis (chronic liver damage).

    • Expanding. A single tumor grows but does not spread elsewhere in the liver until late in the disease.

    • Multifocal. The cancer develops as nodules in several places in the liver.

  • Intrahepatic bile duct cancer (also called intrahepatic cholangiocarcinoma). Cancer that originates in the bile ducts within the liver. Bile ducts are tubes that carry the digestive fluid bile to the gallbladder. Intrahepatic (inside the liver) bile duct cancer accounts for about 10 to 20 percent of primary liver cancers. Bile duct cancer is both difficult to diagnose early and to treat.

  • Angiosarcoma and hemangiosarcoma. Rare cancers that originate in the liver’s blood vessels. Angiosarcomas grow fast and are difficult to treat. Most individuals diagnosed with this form of cancer do not survive more than six months.

  • Hepatoblastoma. Rare cancer that affects children, usually younger than 4 years of age. Treatment with surgery and chemotherapy succeeds about 70 percent of the time and more than 90 percent of the time in early stage hepatoblastoma.  Hepatoblastoma accounts for about 90 percent of liver cancers found in children, according to the NCI.

Most cancers found in the liver are secondary. These cancers are not considered liver cancers but are named after the place they started. The liver is a common site for cancer metastasis because of its role filtering nutrients and all of the body’s blood supply.

In addition to the malignant liver cancers, there are several types of benign (nonspreading) liver tumors that often do not cause problems but can have risks:

  • Hemangioma. Starts in blood vessels. Some tumors bleed and may have to be surgically removed.

  • Hepatic adenoma. Starts in hepatocytes, the primary type of liver cell. Some adenomas cause abdominal pain or blood loss. They could rupture, causing severe blood loss and could possibly lead to liver cancer. Surgical removal may be recommended as a precaution.

  • Focal nodular hyperplasia (FNH). Excess growth of hepatocytes, bile duct cells and connective tissue. It is hard to distinguish these benign tumors from liver cancer unless they are biopsied.

Risk factors and causes of liver cancers

Scientists are not certain what causes liver cancer. They think it begins with damage to the cells’ DNA. They know that hepatitis viruses and certain chemicals can damage the DNA in liver cells.

Many factors can increase the chance of developing liver cancers, but they do not mean a person will get the disease. Some of the major risk factors associated with liver cancer are related to conditions that damage liver cells: hepatitis and cirrhosis.

Hepatitis is inflammation of the liver. There are several types of hepatitis virus, but hepatitis B and hepatitis C are most closely associated with liver cancer. These chronic infections appear to be the most significant cause of hepatocellular cancer (the most common type of liver cancer) worldwide, according to the National Cancer Institute (NCI). Hepatitis is seen less in the United States but is becoming more common. Hepatitis B and C are spread by blood and by direct contact with body fluids. In addition to B and C, there are other types of hepatitis that have not been implicated in liver cancers.

Cirrhosis is the formation of scar tissue in the liver. Cirrhosis is associated with hepatocellular cancer in 50 to 80 percent of patients, according to the NCI. Five percent of people with cirrhosis develop hepatocellular cancer. Cirrhosis develops in the liver because of conditions that damage the tissue. The major causes of cirrhosis are excess alcohol use (the most common cause of cirrhosis in the United States), hepatitis B or C and other diseases such as hemochromatosis, which affects iron storage.

Hepatitis infections and cirrhosis damage are the major risk factors for developing liver cancer. Other risk factors for liver cancer include:

  • Diabetes. Studies also have linked diabetes with an increased risk of liver cancer, although these patients usually have other risk factors.

  • Obesity.

  • Gallbladder diseases. Gallstones and inflammation of the gallbladder may increase the risk of intrahepatic bile duct cancer.

  • Aflatoxins. Substances produced in tropical and subtropical regions by a fungus in wheat, rice, corn, soybeans, peanuts and nuts.

  • Certain uncommon inherited metabolic diseases.

  • Vinyl chloride and thorium dioxide exposure.

  • Long-term use of anabolic steroids. Male hormones taken by some athletes.

  • Birth control pills. Oral contraceptives increase the risk of benign liver tumors and may increase the risk of hepatocellular cancer.

  • Arsenic. A toxic chemical that sometimes is naturally present in drinking water.

  • Smoking. Scientists believe smoking is linked to the disease, but the extent is unknown.

Men are much more likely than women to be diagnosed with liver cancers. Scientists think this is due at least in part to the increased exposure of men to many of the above factors, including alcohol abuse, drug abuse and sexual promiscuity (two risk factors in hepatitis), steroid abuse, smoking and exposure to industrial chemicals such as vinyl chloride.

Signs and symptoms of liver cancers

Liver cancers often have no indicators until the disease is advanced. When signs and symptoms do appear they can be due to many other causes. Possible indicators include:

  • Unexplained weight loss
  • Poor appetite
  • Early satiety (feeling full after eating little)
  • Abdominal pain or swelling
  • Enlargement of the liver (often this cannot be felt until late stages)
  • Jaundice (yellowish discoloration of skin and whites of the eyes)
  • Worsening of liver function in people with either hepatitis or cirrhosis

Some liver tumors produce hormones that can affect other organs besides the liver. These hormones may result in unusual symptoms that cause physicians to suspect an endocrine or nervous system disorder rather than liver cancer. The hormones from liver cancer may cause:

  • Hypercalcemia (high blood calcium levels)
  • Hypoglycemia (low blood sugar levels)
  • Gynecomastia (enlargement of breasts in men)

The high calcium levels can lead to weakness, and low blood sugar levels can cause fainting and possible coma. If an individual has these symptoms, a physician will need to use diagnostic tests to determine the cause, because these symptoms are not specific for primary liver cancer.

Diagnosis methods for liver cancers

Early detection of liver cancers is difficult because of the lack of early symptoms and the lack of diagnostic methods. A physician will take a medical history to note risk factors such as hepatitis, cirrhosis, diabetes and toxic exposure. During a physical examination a physician can seldom feel (palpate) a small tumor because the right rib cage covers most of the liver. A tumor may be large and hard to treat by the time it can be felt.

A special blood test for a protein called alpha-fetoprotein (AFP) can sometimes detect liver cancer. AFP is found in fetal blood but disappears after birth. Its recurrence may indicate liver cancer but can also suggest other diseases. In addition, some liver tumors do not produce much AFP, and when AFP is found the liver cancer is often advanced.

Patients with symptoms of liver cancers may receive:

  • Ultrasound. A painless test using sound waves to create a picture of the liver.

  • CAT scan. A type of x-ray test that creates cross-sectional images of the body. Often a dye is injected to better show the body’s structures.

  • MRI. Use of a machine emitting radio waves and magnetism to create detailed images of internal organs such as the liver. A dye may be injected into the arm to highlight structures.

  • Biopsy. Obtaining a tissue sample from the liver for microscopic examination. This is usually the only method that can prove liver cancer is present, but it may not be needed if the less invasive tests indicate cancer.

Some of these tests may be used to screen for liver cancers, including the AFP blood test and ultrasound. However, such screening may only be performed on patients at increased risk for liver cancers, such as those with cirrhosis or hepatitis B or C.

Treatment options for liver cancers

Options for treating liver cancers depend largely on the extent of the disease. Other factors include age, general physical condition and personal preferences. Treatment will be planned by a cancer care team that may include a medical oncologist, hepatologist (liver specialist), hematologist (physician specializing in disorders of the blood), radiation oncologist, surgeon and dietitian.

The American Cancer Society (ACS) recommends getting a second opinion for liver cancer treatment. Some insurers require second opinions before agreeing to pay for certain therapies. The only cures for liver cancers, according to the ACS, are surgical removal of the tumor or a liver transplant. If these approaches are not possible, treatment may focus on limiting the tumor or relieving pain and other symptoms.

The usual first approach to treating liver cancer is surgery. Physicians may explain treatment approaches to patients by using categories that identify the ability to treat the cancer surgically:

  • Localized resectable. Cancer in part of the liver, potentially curable by surgery.
  • Localized unresectable. Cancer in the liver that surgery cannot completely remove because of its size, location or distribution.
  • Advanced. Cancer that has spread throughout the liver or other structures. Usually this cannot be treated by surgery.

Surgical resection, or partial hepatectomy, is the surgical removal of the involved area of the liver. If all the cancer is removed, this can cure early stage liver cancers. However, usually it is not possible to removal all the cancer because it is too large or has spread to other parts of the body. Resection is more successful in people who have good general health and do not have cirrhosis. The surgery is done in a hospital under general anesthesia. Research is continuing into less invasive techniques where one or several holes are made for a laparoscopic removal of tumors that are small and easily accessible.

Removal of the diseased liver (total hepatectomy) and transplantation of a donated organ is sometimes used with patients who have a few small tumors that cannot all be removed. However, few donor livers are available, and these are usually reserved for more curable diseases, according to the ACS. Scientists hope to make liver transplants more of an option by improving drugs that reduce rejection and by increasing public awareness of the need for donor organs.

In addition to the surgical options, other methods of treating liver cancer include:

  • Tumor ablation. Use of local rather than systemic means to destroy the tumor. This is more likely to be used with patients who have a few small tumors that cannot be cured through resection. Types of ablation include:

    • Radiofrequency ablation (RFA). Temporary insertion into the tumor of a needle-like probe that emits high-energy radio waves.

    • Ethanol ablation (also called alcohol ablation or percutaneous ethanol injection). Injection of alcohol into the tumor.

    • Cryotherapy (also called cryosurgery). Temporary insertion of a cold metal probe that freezes the tumor. Cryosurgery may require general anesthesia.

  • Radiation therapy. The primary type used with liver cancer is external-beam radiation therapy. It is used to ease pain by shrinking the tumor. Higher doses of radiation may damage healthy liver tissue. Newer methods of radiation, called three-dimensional conformal radiation therapy, use a plastic mold to help aim the radiation beams at the tumors more accurately. Radiation therapy also may be combined with the use of radiosensitizers, which can make the cancer cells more susceptible to radiation.

  • Chemotherapy. Use of powerful cancer-killing drugs taken by injection or mouth. In general, liver cancers resist most chemotherapy drugs. Recent studies of radiation combined with certain chemotherapies have shown some improvement for patients with tumors that cannot be removed surgically. Researchers are also studying chemotherapy that is delivered directly to the liver through the hepatic artery, which supplies blood to most tumors.

  • Embolization. Several methods may be used to block blood flow or deliver treatment by way of the hepatic artery, which serves the liver and is usually the artery closest to the site of cancer cells. In hepatic artery embolization, a catheter is inserted into an artery in the groin and threaded up into the liver. Particles of an inert material are injected through the catheter to plug the hepatic artery. Most healthy liver cells are not affected because they get blood from the portal vein. This procedure might not be an option for people with hepatitis, cirrhosis or other liver diseases. Chemoembolization combines hepatic artery embolization with chemotherapy. This can involve either coating the embolization particles with drugs before injection or supplying medication through the catheter before plugging the artery. Radioembolization places radioactive substances into the hepatic artery to target tumors

Prevention methods for liver cancers

Many liver cancers can be prevented by reducing exposure to risk factors, according to the American Cancer Society (ACS). Prevention of hepatitis B and hepatitis C is the most important factor in reducing the risk of liver cancer. Hepatitis viruses are spread:

  • Through unprotected sexual intercourse
  • By needles of intravenous drug abusers
  • Through contaminated blood transfusions
  • By needle sticks and other exposure to contaminated fluids in healthcare settings
  • From infected mother to newborn

Methods of preventing hepatitis include:

  • Practicing safe sex

  • Reducing drug abuse and using needle exchange programs

  • Screening all donated blood and discarding contaminated blood, as is done in the United States and other developed nations

  • Practicing safe handling of needles and other objects in healthcare settings

  • Being vaccinated for hepatitis B. The ACS recommends this vaccination for all children and healthcare workers, as well as and adults who engage in high risk behaviors such as illegal drug use and unprotected sex. Research continues into a vaccine for hepatitis C.

  • Careful screening of people who work in food preparation

The drug most often used to treat hepatitis, interferon, may prevent liver cancer in people infected with hepatitis C. Scientists do not know if interferon can reduce risk of liver cancers in people with hepatitis B. Researchers are studying other antiviral drugs to see if they can prevent liver cancers. In addition, some of these same drugs and drug combinations have shown great promise recently in treating hepatitis C to the point that the virus was undetectable in the bloodstream.

In the United States, alcohol abuse is the chief cause of cirrhosis, which can cause liver cancers. Reducing alcoholism would decrease the number of liver cancers but has been a difficult goal to attain, according to the ACS.

Other ways of preventing liver cancers include curbing exposure to carcinogens such as arsenic and tobacco.

Ongoing research regarding liver cancers

Primary liver cancers have some of the lowest survival rates for all cancers. Much of the ongoing research in the field is directed at treatments that may improve survival. Scientists are pursuing many areas of research to keep improving the survival rate for liver cancers.

New surgical treatments include investigations into laparoscopic surgery for easily reached small tumors. Changes in chemotherapy drugs and how they are used are also being investigated. Radiation therapy is difficult to use on liver tumors, so some studies are trying to improve that by making tumors more responsive to radiation.

Some of the greatest recent advances have come in the area of targeted therapies, which directly target cancer cells. In 2007, a study involving sorafenib, a kinase inhibitor drug approved for kidney cancer, showed increased survival rates when used for liver cancer patients. The study showed a significant improvement in survival time, which for advanced liver cancer meant 11 months instead of 8 months. Biological therapy, which uses the body’s immune system to fight cancer, is also being studied. Interferon is used to treat certain other cancers and is also used to treat hepatitis C. Some studies have shown improvement when interferon was used with hepatitis C patients who developed liver cancer.

There are many clinical trials being conducted for the diagnosis and treatment of liver cancers. Patients should discuss with their personal physician the benefits and risks of enrolling in these trials.

Staging liver cancers

The most common way of staging (describing the extent of) liver cancers is the American Joint Committee on Cancer’s American Joint Committee on Cancer’s TNM System. It includes detailed information about the tumor (T), involvement of lymph nodes (N) and spread or metastasis (M).

A summary of the TNM stages for liver cancers:

  • Stage I. The liver tumor does not invade blood vessels.

  • Stage II. There is one tumor that invades blood vessels, or there are several tumors and all are less than 2 inches (5 centimeters) in diameter.

  • Stage III. There are several tumors, at least one of which is more than 2 inches (5 cm) in diameter, or a tumor invades a branch of the liver’s major blood vessels (portal vein or hepatic vein). Tumors may have invaded a nearby organ other than the gallbladder, or a tumor may have penetrated the lining of the liver or nearby lymph nodes.

  • Stage IV. The liver cancer has spread to other parts of the body.

Physicians use these stages to help determine the best treatment for the disease. The liver cancers that might be cured through surgical removal (resection) if the rest of the organ is healthy are in stages I, II or IIIA, according to the American Cancer Society.

Questions for your doctor about liver cancers

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about liver cancer:

  1. What are the signs of liver cancer?

  2. How does cancer affect liver function?

  3. What tests are used to diagnose liver cancer?

  4. How do I know where my cancer started?

  5. What type of liver cancer do I have?

  6. What stage is my cancer?

  7. What are my treatment options?

  8. What are the best ways to prevent liver cancers?

  9. Is there a genetic link with this type of cancer?

  10. How do I know if the cancer has spread?
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