Liver Cancer

Primary liver cancer begins in the cells of the liver itself. Although many cancers are declining in the United States, new cases of primary liver cancer are increasing and are likely to continue to increase for the next two decades.

Liver cancer also occurs as metastatic cancer, which happens when tumors from other parts of the body spread (metastasize) to the liver. In the United States, most cancer found in the liver spread there after originating elsewhere. Rather than being called liver cancer, this type of cancer in the liver is named after the organ in which it began such as metastatic colon cancer in cancer that starts in the colon and spreads to the liver.

Because liver cancer is rarely discovered early and is difficult to control with current treatments, the prognosis is often poor. Even when treatments fail to provide much improvement, however, they often can help control pain and improve quality of life. But the most important news about primary liver cancer is that you can greatly reduce your risk by protecting yourself from hepatitis infection and cirrhosis, the leading causes of the disease

Signs and Symptoms

Most people don't have signs and symptoms in the early stages of liver cancer, which means the disease may not be detected until it's quite advanced. When symptoms do appear, they may include some or all of the following:

  • Loss of appetite and weight

  • Abdominal pain, especially in the upper right part of your abdomen, that may extend into your back and shoulder

  • Nausea and vomiting

  • General weakness and fatigue

  • An enlarged liver

  • Abdominal swelling (ascites)

  • A yellow discoloration of your skin and the whites of your eyes (jaundice)

Causes

Weighing between 3 and 4 pounds and about the size of a football, your liver is the largest internal organ in your body. It's located in the upper right portion of your abdomen, beneath your diaphragm and above your stomach. Your liver is divided into two main sections (lobes). Each lobe is made up of thousands of smaller lobes (lobules), which are connected to a network of ducts. The lobules are the functioning parts of your liver and perform hundreds of tasks essential for your health and well-being.

Your liver processes most of the nutrients absorbed from your small intestine and determines how much sugar (glucose), protein and fat enter your bloodstream. It also manufactures blood-clotting substances and certain proteins and every day produces nearly a quart of bile a fluid that helps your body digest fats.

Your liver also performs a vital detoxifying function by removing drugs, alcohol and other harmful substances from your bloodstream. At any one time your liver holds about 13 percent of your body's total blood, which enters the liver through two vascular systems: the hepatic artery and portal vein.

Because of the complexity of the liver and its exposure to so many potentially toxic substances, it would seem especially vulnerable to disease. But the liver has an amazing capacity for regeneration it can heal itself by replacing or repairing injured tissue. In addition, healthy cells will take over the function of damaged cells, either indefinitely or until the damage has been repaired. Yet in spite of this, your liver is prone to a number of diseases that can cause serious or irreversible damage. One of these diseases is primary liver cancer.

What happens in liver cancer?

In liver cancer some cells begin to grow abnormally. It's not completely understood why this happens, but researchers believe that cancer starts with damage to DNA the material that contains the instructions for every chemical process in your body, including the rate of cellular growth. DNA damage causes changes in these instructions. One result is that cells may begin to grow out of control and eventually form a tumor a mass of malignant cells.

Factors known to damage DNA in liver cells include:

  • Hepatitis B and C. Worldwide, chronic infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV) is the most common cause of liver cancer. In the United States, hepatitis C infection is responsible for half the new cases of hepatocellular carcinoma (HCC), the most common type of primary liver cancer. Hepatitis C is transmitted primarily through transfusions with blood that hasn't been screened for the virus, through contaminated needles used to inject drugs or, less commonly, through needles used in tattooing or body piercing. In some cases, hepatitis C may be transmitted sexually. Just how it damages DNA isn't well understood. The virus doesn't insert its genetic material into healthy liver cells the way HBV does, but some experts think that the virus may interfere with the action of a gene that prevents cells from reproducing at an accelerated rate. HBV is spread through unprotected sexual contact and through contaminated needles. In addition, women infected with HBV can pass the virus to their unborn children. The virus appears to affect the liver by inserting some of its genetic material into healthy liver cells. This disrupts the normal functioning of the cells and eventually may lead to cancer.

  • Cirrhosis. In the United States, alcohol abuse is the most common cause of cirrhosis, a disease that leads to irreversible scarring in the liver. Hereditary hemochromatosis, which causes excess iron to accumulate in your liver and other tissues, also can lead to cirrhosis.

  • Long-term exposure to aflatoxins. These highly toxic carcinogens are formed when certain crops or foods are contaminated with the fungus Aspergillus flavus. Aflatoxins can damage the p53 gene, which normally works to prevent excessive cell growth. Although the risk from aflatoxins in the United States is small, the toxins have been found in corn and corn products, peanuts and peanut products, cottonseed, milk, Brazil nuts, pecans, pistachios and walnuts. As a result, the Food and Drug Administration has instituted a number of procedures to identify and measure aflatoxins in the food supply.

  • Vinyl chloride and thorium dioxide (Thorotrast). Vinyl chloride is a chemical used to manufacture plastics. Thorotrast was at one time given to people undergoing X-ray tests. Both chemicals are known to play a role in the development of rare cancers that begin in the liver's blood vessels (angiosarcomas or hemangiosarcomas).

  • Arsenic. Drinking water contaminated with arsenic, a known carcinogen, has been implicated in the development of liver cancer.

  • Primary biliary cirrhosis. People with primary biliary cirrhosis, an inflammation of the bile ducts in the liver, have a significantly increased risk of cholangiocarcinoma, a type of primary liver cancer. For that reason, doctors usually recommend routine cancer-screening tests for people with this condition.

  • Ulcerative colitis. This inflammatory condition of the colon and digestive tract leads to changes within the bile ducts and increases the risk of cholangiocarcinoma.

Types of primary liver cancer

Several types of liver cancer exist, each with its own set of causes:

  • Hepatocellular carcinoma (HCC). This is the most common form of primary liver cancer in both children and adults. It starts in the hepatocytes, the main type of liver cell, but can spread in different ways as a single tumor that slowly invades the rest of the liver or as cancer that immediately spreads throughout the entire organ. The most common causes of HCC include cirrhosis, hepatitis B or C infection, and ingestion of aflatoxin-contaminated food.

  • Cholangiocarcinoma. This type of cancer begins in the small bile ducts within the liver. You're at increased risk of developing cholangiocarcinoma if you have gallstones or ulcerative colitis. Certain liver parasites commonly found in parts of Southeast Asia also may contribute to this type of cancer.

  • Hepatoblastoma. This rare type of liver cancer affects children younger than 4 years of age and may be caused by an abnormal gene. Most children with hepatoblastoma can be successfully treated.

  • Angiosarcoma or hemangiosarcoma. These rare cancers begin in the blood vessels of the liver and are associated with exposure to industrial chemicals such as vinyl chloride or the drug thorium dioxide (Thorotrast). They're much less likely to occur today. Medical use of Thorotrast was discontinued nearly 50 years ago, and workers are better protected from exposure to carcinogenic chemicals.

Metastatic Cancer

In the United States, most cancer found in the liver has spread there from another part of the body. Rather than being referred to as liver cancer, this type of cancer is usually named after the organ where it originated and is described as "metastatic." For instance, cancer that has spread to the liver from the colon is referred to as metastatic colon cancer.

Metastatic cancers form when malignant cells detach from the primary cancer and travel through the body in the circulatory or lymphatic system. Because the liver is close to a number of significant organs including the pancreas, gallbladder, stomach, colon, breasts and lungs and because the liver is richly supplied with blood, it's especially vulnerable to metastatic tumors.

Types of Benign Tumors

Noncancerous (benign) tumors also can develop in the liver. They include:

  • Hemangioma. This is the most common type of benign liver tumor. It affects the liver's blood vessels and usually results from a malformation of tissue during fetal development. Most hemangiomas of the liver don't cause signs or symptoms and don't need treatment.

  • Hepatic adenoma. This benign tumor originates in the hepatocytes the main type of liver cell. In most cases, hepatic adenomas don't cause signs or symptoms, but occasionally you may experience abdominal pain, a mass in the abdomen or blood loss. You're more likely to develop this type of benign tumor if you use birth control pills, but simply stopping the pill often causes the tumor to shrink.

  • Focal nodular hyperplasia. This tumor is a combination of several types of cells, including hepatocytes, bile duct cells and connective tissue. Like other benign tumors, it's more common in women than in men and usually doesn't cause signs or symptoms.

Risk Factors

Liver cancer can affect people of all ages and races, but certain factors may increase your risk, including:

  • Sex. Men are twice as likely to develop liver cancer as women are.

  • Race. Asian-Americans have the highest rate of liver cancer in the United States due to high rates of chronic hepatitis B infection. American blacks and Hispanics are more likely to develop liver cancer than whites are, but their risk is more moderate than it is for immigrants from Asian countries where hepatitis B infection is endemic.

  • Age. In the United States, liver cancer occurs most often in people age 60 and older.

  • Chronic infection with HBV or HCV. Chronic infection with hepatitis B or C is by far the most important risk factor for liver cancer. Worldwide, HBV infection is involved in the majority of cases of HCC. In the United States, hepatitis C infection is a greater risk factor.

  • Having cirrhosis. This progressive and irreversible condition causes scar tissue to form in your liver and increases your chances of developing liver cancer.

  • Having diabetes. People with this blood sugar disorder have a greater risk of liver cancer than do people who don't have diabetes. Having both diabetes and hepatitis C infection increases the risk even more.

  • Having certain gene mutations. Doctors have long known that women with mutations in the BRCA1 and BRCA2 genes are more likely to develop breast and ovarian cancer than are women who don't have these genetic defects. Now BRCA1 and BRCA2 mutations have been tied to a moderately increased risk of other cancers, including primary liver cancer.

  • Exposure to aflatoxins. Consuming foods contaminated with aflatoxins greatly increases the risk of liver cancer.

  • Excessive alcohol consumption. Consuming more than a moderate amount of alcohol can lead to irreversible liver damage and increase your risk of liver cancer. Moderate consumption is defined as no more than two drinks a day for men and one for women. A drink is one 4- to 5-ounce glass of wine, 12 ounces of beer or a 1.5-ounce shot of 80-proof distilled spirits.

  • Smoking. Smoking tobacco of any kind makes it more likely that you'll develop liver cancer.

Screening and Diagnosis

No completely accurate screening test for liver cancer exists. Doctors sometimes use a blood test that checks for the presence of alpha-fetoprotein (AFP) a type of protein not normally found in adults to screen people at high risk of the disease. But the test isn't perfect. Not all malignant liver tumors produce AFP, and those that do may be advanced by the time protein levels become elevated. In addition, other types of cancer and even some noncancerous liver diseases can raise AFP levels.

Although AFP screening can detect small tumors in some people, most liver cancer isn't diagnosed early. That's because symptoms usually don't appear until late in the disease and because liver cancers grow quickly. The most common type of liver cancer, HCC, doubles in size every four months. Diagnosis is also difficult because the effects of some liver tumors may resemble those of other medical conditions, and because liver cancer can't be diagnosed using a standard panel of liver tests.

If you experience any of the symptoms of liver cancer, such as unexplained weight loss, persistent abdominal pain or swelling, or jaundice, see your doctor as soon as possible. He or she will interview you about your medical history, perform a physical exam, and will likely recommend one or more of the following tests, each of which has certain advantages and disadvantages:

  • Ultrasound (ultrasonography). This noninvasive test, which doesn't expose you to radiation or dyes, uses sound waves to produce a picture of internal organs, including the liver. Ultrasound is painless and usually takes less than 30 minutes. While you lie on a bed or examining table, a wand-shaped device (transducer) is placed on your body. It emits sound waves that are reflected from your liver and transformed into a computer image. Ultrasound is especially good at providing information about the shape, texture and makeup of tumors.

  • Computerized tomography (CT) scan. This test uses X-rays to produce cross-sectional images of your body. You may also have a variation of the test known as a CT angiogram in which contrast dye is injected into an artery in your liver. X-rays then track the dye as it flows through the blood vessels in your liver. A CT angiogram, which may take up to an hour to perform, can provide detailed information on the number and location of liver tumors, but a CT scan exposes you to more radiation than conventional X-rays do, and some people may experience an allergic reaction to the contrast dye.

  • Magnetic resonance imaging (MRI). Instead of X-rays, MRI creates images using a magnetic field and radio waves. Sometimes a contrast dye also may be used. The test can take from 15 minutes to an hour. You may find an MRI more uncomfortable than a CT scan because you're enclosed in a tube that is quite confining and because the machine generates a thumping noise that many people find disturbing. Headphones or earphones can help with the noise, and if you're very claustrophobic, your doctor may recommend medication to help you relax. Newer MRIs can show images of the ducts that transport bile from the liver to the upper part of the small intestine (duodenum) as well as of the arteries and veins within the liver.

  • Liver biopsy.


    In this procedure, a sample of tissue is removed from your liver and examined under a microscope. Liver biopsy is considered the only definitive way to diagnose liver cancer. Your doctor may use a thin needle or a lighted instrument (laparoscope) to obtain the sample. If the tumor is small, an ultrasound or CT scan is often used to help pinpoint the area to be biopsied. A needle biopsy is the simpler procedure, with less risk of bleeding, but it doesn't always provide enough cells for an accurate evaluation. Because the liver is so well supplied with blood vessels, bleeding is the most common risk of a biopsy, but bruising and infection also can occur.

  • Blood tests. If tests reveal that you have liver cancer, your doctor may perform additional blood tests to check the condition of the liver tissue not affected by cancer. This information may play a role in determining the best treatment for you.

Treatment

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