What is Liver cancer

Cancers that start in the liver are called liver cancer (primary liver cancer) ¹.

Your liver is the largest organ inside your body. You cannot live without your liver because your liver helps your body digest food, store energy, and remove poisons.

Your liver lie under your right ribs just beneath your right lung. It is divided into lobes.

A large right lobe and a smaller left lobe and two minor lobes, the quadrate lobe and the caudate lobe (Figure 2). Each lobe is separated into many tiny hepatic lobules, the liver’s functional units (Figure 3).

The liver is made up mainly of cells called hepatocytes. It also is made up of other types of cells, including cells that line its blood vessels and cells that line small tubes in the liver called bile ducts. The bile ducts extend out of the liver and carry bile from the liver to the gallbladder or directly to the intestines.

These different types of cells in the liver can form several types of malignant (cancerous) and benign (non-cancerous) tumors. These tumors have different causes, are treated differently, and have a different prognosis (outlook).

How common is liver cancer ?

The American Cancer Society’s estimates for primary liver cancer and intrahepatic bile duct cancer in the United States for 2017 are ²:

• About 40,710 new cases (29,200 in men and 11,510 in women) will be diagnosed
• About 28,920 people (19,610 men and 9,310 women) will die of these cancers

Liver cancer incidence has more than tripled since 1980. However, rates in young adults have recently begun to decline. Liver cancer death rates have increased by almost 3% per year since 2000. Liver cancer is seen more often in men than in women.

Where is liver cancer more common ?

Liver cancer is much more common in countries in sub-Saharan Africa and Southeast Asia than in the US ². In many of these countries it is the most common type of cancer. More than 700,000 people are diagnosed with this cancer each year throughout the world. Liver cancer is also a leading cause of cancer deaths worldwide, accounting for more than 600,000 deaths each year.

Prevention of liver cancer

The most effective way to reduce the worldwide burden of liver cancer is to prevent it from happening in the first place. Some scientists believe that vaccinations and improved treatments for hepatitis could prevent about half of liver cancer cases worldwide. Researchers are studying ways to prevent or treat hepatitis infections before they cause liver cancers. Research into developing a vaccine to prevent hepatitis C is ongoing. Progress is also being made in treating chronic hepatitis.

Avoiding and treating hepatitis infections

Worldwide, the most significant risk factor for liver cancer is chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). These viruses can spread from person to person through sharing contaminated needles (such as in drug use) and through unprotected sex, so some of these cancers may be prevented by not sharing needles and by using safer sex practices (such as consistent use of condoms).

A vaccine to help prevent hepatitis B virus infection has been available since the early 1980s. The US Centers for Disease Control and Prevention (CDC) recommends that all children, as well as adults at risk get this vaccine to reduce the risk of hepatitis and liver cancer.

There is no vaccine for hepatitis C virus. Preventing hepatitis C virus infection, as well as hepatitis B virus infection in people who have not been immunized, is based on understanding how these infections occur. These viruses can be spread through sharing contaminated needles (such as in drug use), unprotected sex, and through childbirth.

Blood transfusions were once a major source of hepatitis infection as well. But because blood banks in the United States test donated blood to look for these viruses, the risk of getting a hepatitis infection from a blood transfusion is extremely low.

People at high risk for hepatitis B virus (HBV) or hepatitis C virus (HCV) should be tested for these infections so they can be watched for liver disease and treated if needed.

According to the CDC, you are at risk of having hepatitis B if you:

• Have sex with someone who is infected
• Have multiple sex partners
• Have a sexually transmitted disease
• Are a man who has sex with other men
• Inject drugs
• Live with a person who has chronic hepatitis B virus
• Travel to countries where many people have hepatitis B virus
• Are exposed to blood on the job
• Get long-term hemodialysis

A baby born to a mother that is infected with hepatitis B virus is also at risk for being infected.

The CDC recommends that you get tested for hepatitis C virus if any of the following are true:

• You were born from 1945 through 1965 (this is because most of the people in the US that are infected with hepatitis C virus were born in these years)
• You ever injected drugs (even just once or a long time ago)
• You needed medicine for a blood clotting problem before 1987
• You received a blood transfusion or organ transplant before July 1992 (when blood and organs started being screened for HCV)
• You are on long-term hemodialysis
• You are infected with HIV

Treatment of chronic hepatitis C virus infection can eliminate the virus in many people.

A number of drugs are used to treat chronic hepatitis B virus infection. These drugs reduce the number of viruses in the blood and lessen liver damage. Although they do not cure the disease, they lower the risk of cirrhosis and might lower the risk of liver cancer, as well.

Limiting alcohol and tobacco use

Drinking alcohol can lead to cirrhosis, which in turn, can lead to liver cancer. Not drinking alcohol or drinking in moderation could help prevent liver cancer.

Since smoking also increases the risk of liver cancer, not smoking will also prevent some of these cancers. If you smoke, quitting will help lower your risk of this cancer, as well as many other cancers and life-threatening diseases.

Getting to and staying at a healthy weight

Avoiding obesity might be another way to help protect against liver cancer. People who are obese are more likely to have fatty liver disease and diabetes, both of which have been linked to liver cancer.

Limiting exposure to cancer-causing chemicals

Changing the way certain grains are stored in tropical and subtropical countries could reduce exposure to cancer-causing substances such as aflatoxins. Many developed countries already have regulations to prevent and monitor grain contamination.

Most developed countries also have regulations to protect consumers and workers from certain chemicals known to cause liver cancer. For example, the US Environmental Protection Agency (EPA) limits the allowable level of arsenic in drinking water in the United States. But this may continue to be a problem in areas of the world where naturally occurring arsenic commonly gets into drinking water.

Treating diseases that increase liver cancer risk

Certain inherited diseases can cause cirrhosis of the liver, increasing a person’s risk for liver cancer. Finding and treating these diseases early in life could lower this risk. For example, all children in families with hemochromatosis should be screened for the disease and treated if they have it. Treatment regularly removes small amounts of blood to lower the amount of excess iron in the body.

Figure 1. Normal liver

Figure 2. Liver anatomy

Figure 3. Liver lobule

Note: (a) Cross section of a hepatic lobule. (b) Enlarged longitudinal section of a hepatic lobule. (c) Light micrograph of hepatic lobules in cross section.

Benign liver tumors

Benign tumors sometimes grow large enough to cause problems, but they do not grow into nearby tissues or spread to distant parts of the body. If they need to be treated, the patient can usually be cured with surgery.

Hemangioma

The most common type of benign liver tumor, hemangiomas, start in blood vessels. Most hemangiomas of the liver cause no symptoms and do not need treatment. But some may bleed and need to be removed surgically.

Hepatic adenoma

Hepatic adenoma is a benign tumor that starts from hepatocytes (the main type of liver cell). Most cause no symptoms and do not need treatment. But some eventually cause symptoms, such as pain or a mass in the abdomen (stomach area) or blood loss. Because there is a risk that the tumor could rupture (leading to severe blood loss) and a small risk that it could eventually develop into liver cancer, most experts will usually advise surgery to remove the tumor if possible.

Using certain drugs may increase the risk of getting these tumors. Women have a higher chance of having one of these tumors if they take birth control pills, although this is rare. Men who use anabolic steroids may also develop these tumors. Adenomas may shrink when the drugs are stopped.

Focal nodular hyperplasia

Focal nodular hyperplasia is a tumor-like growth made up of several cell types (hepatocytes, bile duct cells, and connective tissue cells). Although focal nodular hyperplasia tumors are benign, it can be hard to tell them apart from true liver cancers, and doctors sometimes remove them when the diagnosis is unclear. If you have symptoms from an focal nodular hyperplasia tumor, it can be removed with surgery.

Both hepatic adenomas and focal nodular hyperplasia tumors are more common in women than in men.

Types of Primary Liver Cancer

A cancer that starts in the liver is called primary liver cancer. There is more than one kind of primary liver cancer.

Hepatocellular carcinoma (hepatocellular cancer)

This is the most common form of liver cancer in adults about 90 percent of liver cancers ³.

Hepatocellular cancer can have different growth patterns:

• Some begin as a single tumor that grows larger. Only late in the disease does it spread to other parts of the liver.
• A second type seems to start as many small cancer nodules throughout the liver, not just a single tumor. This is seen most often in people with cirrhosis (chronic liver damage) and is the most common pattern seen in the United States.

Using a microscope, doctors can distinguish several subtypes of hepatocellular cancer. Most often these subtypes do not affect treatment or prognosis (outlook). But one of these subtypes, fibrolamellar, is important to recognize. This type is rare, making up less than 1% of hepatocellular cancers ⁴. This type is most often seen in women younger than age 35, and often the rest of the liver is not diseased ⁵. This subtype generally has a better outlook than other forms of hepatocellular cancer ⁵.

Intrahepatic cholangiocarcinoma (bile duct cancer)

About 10% to 20% of cancers that start in the liver are intrahepatic cholangiocarcinomas ⁴. These cancers start in the cells that line the small bile ducts (tubes that carry bile to the gallbladder) within the liver. (Most cholangiocarcinomas actually start in the bile ducts outside the liver.)

Although the rest of this article deals mainly with hepatocellular cancers, cholangiocarcinomas are often treated the same way.

Angiosarcoma and hemangiosarcoma

These are rare cancers that begin in cells lining the blood vessels of the liver. People who have been exposed to vinyl chloride or to thorium dioxide (Thorotrast) are more likely to develop these cancers ⁴. Some other cases are thought to be caused by exposure to arsenic or radium, or to an inherited condition known as hereditary hemochromatosis. In about half of all cases, no likely cause can be identified.

These tumors grow quickly and are usually too widespread to be removed surgically by the time they are found. Chemotherapy and radiation therapy may help slow the disease, but these cancers are usually very hard to treat. These cancers are treated like other sarcomas.

Hepatoblastoma

This is a very rare kind of cancer that develops in children, usually in those younger than 4 years old ⁴. The cells of hepatoblastoma are similar to fetal liver cells. About 2 out of 3 children with these tumors are treated successfully with surgery and chemotherapy, although the tumors are harder to treat if they have spread outside the liver.

Secondary liver cancer (metastatic liver cancer)

Most of the time when cancer is found in the liver it did not start there but has spread (metastasized) from somewhere else in the body, such as the pancreas, colon, stomach, breast, or lung. Because this cancer has spread from its original (primary) site, it is a secondary liver cancer. These tumors are named and treated based on their primary site (where they started). For example, cancer that started in the lung and spread to the liver is called lung cancer with spread to the liver, not liver cancer, and it is treated as lung cancer.

In the United States and Europe, secondary (metastatic) liver tumors are more common than primary liver cancer ⁴. The opposite is true for many areas of Asia and Africa ⁴.

Most of the remaining content refers only to hepatocellular carcinoma.

Causes of liver cancer

Although several risk factors for hepatocellular cancer are known (see Liver Cancer Risk Factors below), exactly how these may lead normal liver cells to become cancerous is only partially understood.

Cancers develop when a cell’s DNA is damaged. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. Some genes have instructions for controlling when cells grow, divide into new cells, and die.

• Some genes that tell cells to grow and divide are called oncogenes.
• Genes that slow down cell division or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. Several different genes usually need to have changes for a cell to become cancerous.

Certain chemicals that cause liver cancer, such as aflatoxins, are known to damage the DNA in liver cells. For example, studies have shown that aflatoxins can damage the TP53 tumor suppressor gene, which normally works to prevent cells from growing too much. Damage to the TP53 gene can lead to increased growth of abnormal cells and formation of cancers.

Infection of liver cells with hepatitis viruses can also damage DNA. These viruses have their own DNA, which carries instructions on how to infect cells and produce more viruses. In some patients, this viral DNA can insert itself into a liver cell’s DNA, where it may affect the cell’s genes. But scientists still don’t know exactly how this might lead to cancer.

Liver cancer clearly has many different causes, and there are undoubtedly many different genes involved in its development. It is hoped that a more complete understanding of how liver cancers develop will help doctors find ways to better prevent and treat them.

Liver Cancer Risk Factors

A risk factor is anything that affects your chance of getting a disease, such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

But risk factors don’t tell us everything. Having a risk factor, or even several risk factors, does not mean that you will get the disease. And some people who get the disease may have few or no known risk factors.

Scientists have found several risk factors that make a person more likely to develop hepatocellular carcinoma.

Gender

Hepatocellular carcinoma is much more common in males than in females. Much of this is probably because of behaviors affecting some of the risk factors described below. The fibrolamellar subtype of hepatocellular carcinoma is more common in women.

Race/ethnicity

In the United States, Asian Americans and Pacific Islanders have the highest rates of liver cancer, followed by American Indians/Alaska Natives and Hispanics/Latinos, African Americans, and whites.

Being infected with certain types of the hepatitis virus can cause hepatitis and increase the risk of liver cancer.

• Hepatitis A
• Hepatitis B
• Hepatitis C
• Hepatitis D
• Hepatitis E
• Hepatitis G

Hepatitis is most commonly caused by the hepatitis virus. Hepatitis is a disease that causes inflammation (swelling) of the liver. Damage to the liver from hepatitis that lasts a long time can increase the risk of liver cancer.

There are six types of the hepatitis virus ⁶. Hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV) are the three most common types. These three viruses cause similar symptoms, but the ways they spread and affect the liver are different.

The Hepatitis A vaccine and the hepatitis B vaccine prevent infection with hepatitis A and hepatitis B. There is no vaccine to prevent infection with hepatitis C. If a person has had one type of hepatitis in the past, it is still possible to get the other types.

Hepatitis viruses include:

• Hepatitis A

Hepatitis A is caused by eating food or drinking water infected with hepatitis A virus. It does not lead to chronic disease. People with hepatitis A usually get better without treatment.

• Hepatitis B

Hepatitis B is caused by contact with the blood, semen, or other body fluid of a person infected with hepatitis B virus. It is a serious infection that may become chronic and cause scarring of the liver (cirrhosis). This may lead to liver cancer. Blood banks test all donated blood for hepatitis B, which greatly lowers the risk of getting the virus from blood transfusions.

• Hepatitis C

Hepatitis C is caused by contact with the blood of a person infected with hepatitis C virus. Hepatitis C may range from a mild illness that lasts a few weeks to a serious, lifelong illness. Most people who have hepatitis C develop a chronic infection that may cause scarring of the liver (cirrhosis). This may lead to liver cancer. Blood banks test all donated blood for hepatitis C, which greatly lowers the risk of getting the virus from blood transfusions.

• Hepatitis D

Hepatitis D develops in people already infected with hepatitis B. It is caused by hepatitis D virus (HDV) and is spread through contact with infected blood or dirty needles, or by having unprotected sex with a person infected with HDV. Hepatitis D causes acute hepatitis.

• Hepatitis E

Hepatitis E is caused by hepatitis E virus (HEV). Hepatitis E can be spread through oral- anal contact or by drinking infected water. Hepatitis E is rare in the United States.

• Hepatitis G

Being infected with hepatitis G virus (HGV) has not been shown to cause liver cancer.

Chronic viral hepatitis (Hepatitis B or Hepatitis C)

Worldwide, the most common risk factor for liver cancer is chronic (long-term) infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). These infections lead to cirrhosis of the liver and are responsible for making liver cancer the most common cancer in many parts of the world.

In the United States, Europe and Japan infection with hepatitis C is the more common cause of hepatocellular carcinoma ⁷, while in Asia and Africa, hepatitis B is more common ⁸. People infected with both viruses have a high risk of developing chronic hepatitis, cirrhosis, and liver cancer. The risk is even higher if they are heavy drinkers (at least 6 standard drinks a day).

The annual incidence of hepatocellular carcinoma in hepatitis B virus carriers is 0.5% to 1% per year in patients without cirrhosis and 2.5% per year in patients with cirrhosis. The relative risk of hepatocellular carcinoma is 100 (i.e., carriers of hepatitis B virus are 100 times more likely to develop hepatocellular carcinoma than uninfected persons) ⁹, ¹⁰.

In a single, prospective, population-based study that included 12,008 patients, the presence of anti-HCV positivity conferred a twentyfold increased risk of hepatocellular carcinoma compared with persons who were anti-HCV negative ¹¹. Hepatocellular carcinoma may occur in hepatitis C virus-infected patients with bridging fibrosis, even in the absence of overt cirrhosis ¹². However, the risk is highest among patients with hepatitis C virus-related established cirrhosis, which has an incidence rate of hepatocellular carcinoma of 2% to 8% per year ¹³.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) can spread from person to person through sharing contaminated needles (such as in drug use), unprotected sex, or childbirth. They can also be passed on through blood transfusions, although this is very rare in the United States since the start of blood product testing for these viruses. In developing countries, children sometimes contract hepatitis B infection from prolonged contact with family members who are infected.

Hepatitis B virus is more likely to cause symptoms, such as a flu-like illness and a yellowing of the eyes and skin (jaundice). But most people recover completely from hepatitis B virus infection within a few months. Only a very small percentage of adults become chronic carriers (and have a higher risk for liver cancer). Infants and small children who become infected have a higher risk of becoming chronic carriers.

Hepatitis C virus, on the other hand, is less likely to cause symptoms. But most people with hepatitis C virus develop chronic infections, which are more likely to lead to liver damage or even cancer.

Other viruses, such as the hepatitis A virus and hepatitis E virus, can also cause hepatitis. But people infected with these viruses do not develop chronic hepatitis or cirrhosis, and do not have an increased risk of liver cancer.

Cirrhosis

Cirrhosis is a disease in which liver cells become damaged and are replaced by scar tissue. People with cirrhosis have an increased risk of liver cancer. Most (but not all) people who develop liver cancer already have some evidence of cirrhosis.

There are several possible causes of cirrhosis. Most cases in the United States occur in people who abuse alcohol or have chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections.

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease, a condition in which people who consume little or no alcohol develop a fatty liver, is common in obese people. People with a type of this disease known as non-alcoholic steatohepatitis (NASH) might go on to develop cirrhosis.

Primary biliary cirrhosis

Some types of autoimmune diseases that affect the liver can also cause cirrhosis. For example, there is also a disease called primary biliary cirrhosis. In primary biliary cirrhosis, the bile ducts in the liver are damaged and even destroyed which can lead to cirrhosis. People with advanced primary biliary cirrhosis have a high risk of liver cancer ¹⁴.

Inherited metabolic diseases

Certain inherited metabolic diseases can lead to cirrhosis.

People with hereditary hemochromatosis absorb too much iron from their food. The iron settles in tissues throughout the body, including the liver. If enough iron builds up in the liver, it can lead to cirrhosis and liver cancer.

Heavy alcohol use

Alcohol abuse is a leading cause of cirrhosis in the United States, which in turn is linked with an increased risk of liver cancer. However, the true incidence of hepatocellular carcinoma in alcoholic cirrhosis is unknown because most epidemiology reports on this subject were published before the identification of hepatitis C virus (HCV) infections ¹⁵.

Obesity

Being obese (very overweight) increases the risk of developing liver cancer. This is probably because it can result in fatty liver disease and cirrhosis.

Type 2 diabetes

Type 2 diabetes has been linked with an increased risk of liver cancer, usually in patients who also have other risk factors such as heavy alcohol use and/or chronic viral hepatitis. This risk may be increased because people with type 2 diabetes tend to be overweight or obese, which in turn can cause liver problems.

Metabolic syndrome

The risk factors associated with metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and obesity, have been recognized as potential causes of nonalcoholic hepatosteatosis, cirrhosis, and hepatocellular carcinoma. However, no study to date has followed a sufficiently large group of these patients for long enough to describe the incidence of hepatocellular carcinoma caused by metabolic syndrome ¹⁶.

Hemochromatosis

Hemochromatosis is a significant risk factor for hepatocellular carcinoma and has an increased relative risk twenty times that of the normal population ¹⁷.

Certain rare diseases

Diseases that increase the risk of liver cancer include:

• Tyrosinemia
• Alpha1-antitrypsin deficiency
• Porphyria cutanea tarda
• Glycogen storage diseases
• Wilson disease

Aflatoxins B1

Aflatoxin B1 is produced by fungi of the Aspergillus species and is a common contaminant of peanuts, wheat, soybeans, ground nuts, corn, and rice and vegetables in some parts of Asia and Africa. Storage in a moist, warm environment can lead to the growth of this fungus. Although this can occur almost anywhere in the world, it is more common in warmer and tropical countries. Developed countries such as the United States and those in Europe regulate the content of aflatoxins B1 in foods through testing.

Long-term exposure to these substances is a major risk factor for liver cancer. The risk is increased by three fold in people with hepatitis B or C infections ¹⁸.

Vinyl chloride and thorium dioxide (Thorotrast)

Exposure to these chemicals raises the risk of angiosarcoma of the liver. It also increases the risk of developing cholangiocarcinoma and hepatocellular cancer, but to a far lesser degree. Vinyl chloride is a chemical used in making some kinds of plastics. Thorotrast is a chemical that in the past was injected into some patients as part of certain x-ray tests. When the cancer-causing properties of these chemicals were recognized, steps were taken to eliminate them or minimize exposure to them. Thorotrast is no longer used, and exposure of workers to vinyl chloride is strictly regulated.

Anabolic steroids

Anabolic steroids are male hormones used by some athletes to increase their strength and muscle mass. Long-term anabolic steroid use can slightly increase the risk of hepatocellular cancer. Cortisone-like steroids, such as hydrocortisone, prednisone, and dexamethasone, do not carry this same risk.

Arsenic

Drinking water contaminated with naturally occurring arsenic, such as that from some wells, over a long period of time increases the risk of some types of liver cancer. This is more common in parts of East Asia, but it might also be a concern in some areas of the United States.

Infection with parasites

Infection with the parasite that causes schistosomiasis can cause liver damage and is linked to liver cancer. This parasite is not found in the US, but infection can occur in Asia, Africa, and South America.

Tobacco use

Smoking increases the risk of liver cancer. Former smokers have a lower risk than current smokers, but both groups have a higher risk than those who never smoked.

Factors with unclear effects on liver cancer risk

Birth control pills

In rare cases, birth control pills, also known as oral contraceptives, can cause benign tumors called hepatic adenomas. But it is not known if they increase the risk of hepatocellular cancer. Some of the studies that have looked at this issue have suggested there may be a link, but most of the studies were not of high quality and looked at types of pills that are no longer used. Current birth control pills use different types of estrogens, different estrogen doses, and different combinations of estrogens with other hormones. It is not known if the newer pills increase liver cancer risk.

Liver cancer symptoms and signs

Signs and symptoms of liver cancer often do not show up until the later stages of the disease, but sometimes they may show up sooner. If you go to your doctor when you first notice symptoms, your cancer might be diagnosed earlier, when treatment is most likely to be helpful. Some of the most common symptoms of liver cancer are ¹⁹:

• Weight loss (without trying)
• Loss of appetite
• Feeling very full after a small meal
• Nausea or vomiting
• An enlarged liver, felt as a mass under the ribs on the right side
• An enlarged spleen, felt as a mass under the ribs on the left side
• Pain in the abdomen or near the right shoulder blade
• Swelling or fluid build-up in the abdomen
• Itching
• Yellowing of the skin and eyes (jaundice)

Some other symptoms can include fever, enlarged veins on the belly that can be seen through the skin, and abnormal bruising or bleeding.

People who have chronic hepatitis or cirrhosis may feel worse than usual or just have changes in lab test results, such as alpha-fetoprotein (AFP) levels.

Some liver tumors make hormones that act on organs other than the liver. These hormones may cause:

• High blood calcium levels (hypercalcemia), which can cause nausea, confusion, constipation, weakness, or muscle problems
• Low blood sugar levels (hypoglycemia), which can cause fatigue or fainting
• Breast enlargement (gynecomastia) and/or shrinkage of the testicles in men
• High counts of red blood cells (erythrocytosis) which can cause someone to look red and flushed
• High cholesterol levels

Many of the signs and symptoms of liver cancer can also be caused by other conditions, including other liver problems. Still, if you have any of these problems, it’s important to see your doctor right away so the cause can be found and treated, if needed.

Can Liver Cancer Be Found Early ?

It is often hard to find liver cancer early because signs and symptoms often do not appear until it is in its later stages. Small liver tumors are hard to detect on a physical exam because most of the liver is covered by the right rib cage. By the time a tumor can be felt, it might already be quite large.

There are no widely recommended screening tests for liver cancer in people who are not at increased risk. (Screening is testing for cancer in people without any symptoms.) But testing might be recommended for some people at higher risk.

Many patients who develop liver cancer have long-standing cirrhosis (scar tissue formation from liver cell damage). Doctors may do tests to look for liver cancer if a patient with cirrhosis gets worse for no apparent reason.

For people at higher risk of liver cancer due to cirrhosis (from any cause) or chronic hepatitis B infection (even without cirrhosis), some experts recommend screening for liver cancer with alpha-fetoprotein (AFP) blood tests and ultrasound exams every 6 to 12 months. In some studies, screening was linked to improved survival from liver cancer.

Ultrasound uses sound waves to take pictures of internal organs.

Alpha-fetoprotein is a protein that can be present at increased levels in patients with liver cancer. But looking at alpha-fetoprotein levels isn’t a perfect test for liver cancer. Many patients with early liver cancer have normal alpha-fetoprotein levels. Also, alpha-fetoprotein levels can be increased from other kinds of cancer as well as some non-cancerous liver conditions.

The American Cancer Society does not have recommendations for liver cancer screening ²⁰.

How is liver cancer diagnosed ?

If you have some of the signs and symptoms of liver cancer, your doctor will try to find if they are caused by liver cancer or something else.

Medical history and physical exam

Your doctor will ask about your medical history to check for risk factors and learn more about your symptoms. Your doctor will also examine you for signs of liver cancer and other health problems, probably paying special attention to your abdomen and checking your skin and the whites of your eyes looking for jaundice (a yellowish color).

If symptoms and/or the results of the physical exam suggest you might have liver cancer, other tests will probably be done. These might include imaging tests, lab tests, and other procedures.

Imaging tests

Imaging tests use x-rays, magnetic fields, or sound waves to create pictures of the inside of your body. Imaging tests are done for a number of reasons, including:

• To help find suspicious areas that might be cancerous
• To help diagnose liver cancer
• To help a doctor guide a biopsy needle into a suspicious area to take a sample
• To learn how far cancer might have spread
• To help guide certain treatments in the liver
• To help determine if treatment has been effective
• To look for a possible recurrence of the cancer

People who have (or may have) liver cancer may get one or more of the following tests.

Ultrasound

Ultrasound is often the first test used to look at the liver.

Ultrasound (ultrasonography) is the use of sound waves to create an image on a video screen. This test can show masses (tumors) growing in the liver, which then can be tested for cancer, if needed.

Computed tomography (CT)

The CT scan is an x-ray test that produces detailed cross-sectional images of your body. A CT scan of the abdomen can help identify many types of liver tumors. It can provide precise information about the size, shape, and position of any tumors in the liver or elsewhere in the abdomen, as well as nearby blood vessels. CT scans can also be used to guide a biopsy needle precisely into a suspected tumor (called a CT-guided needle biopsy). If you are found to have liver cancer, a CT of your chest may also be done to look for possible spread to the lungs.

Magnetic resonance imaging (MRI)

Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body.

MRI scans can be very helpful in looking at liver tumors. Sometimes they can tell a benign tumor from a malignant one. They can also be used to look at blood vessels in and around the liver, and can help show if liver cancer has spread to other parts of the body.

Angiography

An angiogram is an x-ray test that looks at blood vessels. Contrast medium, or dye, is injected into an artery to outline blood vessels while x-ray images are taken.

Angiography can be used to show the arteries that supply blood to a liver cancer, which can help doctors decide if a cancer can be removed and to help plan the operation. It can also be used to help guide some types of non-surgical treatment, such as embolization (see the section Embolization Therapy for Liver Cancer).

Angiography can be uncomfortable because a small catheter (a flexible hollow tube) must be put into the artery leading to the liver to inject the dye. Usually the catheter is put into an artery in your groin and threaded up into the liver artery. You have to stay very still while the catheter is in place. A local anesthetic is often used to numb the area before inserting the catheter. Then the dye is injected quickly to outline all the vessels while the x-rays are being taken.

Angiography may also be done with a CT scanner (CT angiography) or an MRI scanner (MR angiography). These techniques are often used instead of x-ray angiography because they can give information about the blood vessels in the liver without the need for a catheter in the artery. You will still need an IV line so that a contrast dye can be injected into the bloodstream during the imaging.

Bone scan

A bone scan can help look for cancer that has spread (metastasized) to bones. Doctors don’t usually order this test for people with liver cancer unless you have symptoms such as bone pain, or if there’s a chance you may be eligible for a liver transplant to treat your cancer. .

Other tests and procedures

Other types of tests may be done if your doctor thinks you might have liver cancer but the imaging test results aren’t conclusive.

Laparoscopy

Laparoscopy can be used for liver cancer:

• To help doctors confirm a diagnosis of cancer through biopsy
• To confirm the stage or (extent) of the cancer
• To help plan surgery or other treatments

Laparoscopy is usually done at an outpatient surgery center. In this procedure, a doctor inserts a thin, lighted tube with a small video camera on the end through a small incision (cut) in the front of the abdomen to look at the liver and other internal organs. (Sometimes more than one cut is made.) This procedure is done in the operating room. Usually you are under general anesthesia (in a deep sleep), although sometimes the person may just be sedated (made sleepy) and the area of the incision will be numbed.

Because the surgeon only makes a small incision to insert the tubes, you should not have much pain after surgery. You should be able to go home after you recover from the anesthesia.

Biopsy

A biopsy is the removal of a sample of tissue to see if it is cancer. Sometimes, the only way to be certain that liver cancer is present is to take a biopsy and look at it under a microscope.

But in some cases, doctors can be fairly certain that a person has liver cancer based on the results of imaging tests such as CT and MRI scans. In these cases, a biopsy may not be needed. Doctors are often concerned that sticking a needle into the tumor or otherwise disturbing it without completely removing it might help cancer cells spread to other areas. This is a major concern if a liver transplant might be an option to try to cure the cancer, as any spread of the cancer might make the person ineligible for a transplant. That is why some experts recommend that patients who could be transplant candidates only have biopsies done at the center where the transplant will be done.

If a biopsy is needed, it can be done in several ways.

• Needle biopsy: A hollow needle is placed through the skin in the abdomen and into the liver. The skin is first numbed with local anesthesia before the needle is placed. Different-sized needles may be used.
• Laparoscopic biopsy: Biopsy specimens can also be taken during laparoscopy. This lets the doctor see the surface of the liver and take samples of abnormal-appearing areas.
• Surgical biopsy: An incisional biopsy (removing a piece of the tumor) or an excisional biopsy (removing the entire tumor and some surrounding normal liver tissue) can be done during an operation.

Lab tests

Your doctor could order lab tests for a number of reasons:

• To help diagnose liver cancer
• To help determine what might have caused your liver cancer
• To learn how well your liver is working, which can affect what types of treatments you can have
• To get an idea of your general health and how well your other organs are working, which also could affect what types of treatments you can have
• To see how well treatment is working
• To look for signs that the cancer has come back after treatment

Alpha-fetoprotein blood (AFP) test

AFP is normally present at high levels in the blood of fetuses but drops to low levels shortly after birth. Levels in adults can go up from liver disease, liver cancer, or other cancers.

If AFP levels are very high in someone with a liver tumor, it can be a sign that liver cancer is present. But because liver cancer isn’t the only reason for high AFP levels and many patients with early liver cancer have normal levels of AFP, it isn’t very helpful in determining if a liver mass might be cancer.

This test is sometimes useful in people already diagnosed with liver cancer. The AFP level can help determine what treatment might be an option. During treatment, the test can be used to help give an idea of how well it is working, as the AFP level should go down if treatment is effective. The test can be used after treatment as well, to look for possible signs that the cancer has come back (recurred).

Other blood tests

Liver function tests (LFTs): Because liver cancer often develops in livers already damaged by hepatitis and/or cirrhosis, doctors need to know the condition of your liver before starting your treatment. A series of blood tests can measure levels of certain substances in your blood that show how well your liver is working.

If the part of your liver not affected by cancer isn’t working well, you might not be able to have surgery to try to cure the cancer, as the surgery might require removal of a large part of your liver. This is a common problem in people with liver cancer.

Blood clotting tests: The liver also makes proteins that help blood clot when you bleed. A damaged liver might not make enough of these clotting factors, which could increase your risk of bleeding. Your doctor may order blood tests such as a prothrombin time (PT) to help assess this risk.

Tests for viral hepatitis: Your doctor might order blood tests to check for hepatitis B and C.

Kidney function tests: Tests of blood urea nitrogen (BUN) and creatinine levels are often done to assess how well your kidneys are working.

Complete blood count (CBC): This test measures levels of red blood cells (which carry oxygen throughout your body), white blood cells (which fight infections), and platelets (which help the blood clot). It gives an idea of how well the bone marrow (where new blood cells are made) is functioning.

Blood chemistry tests and other tests: Blood chemistry tests check the levels of a number of substances in the blood, some of which might be affected by liver cancer. For example, liver cancer can raise blood levels of calcium, while blood glucose levels may fall. Liver cancer can also sometimes raise cholesterol levels, so this may be checked as well.

Liver Cancer Stages

The stage of liver cancer is a description of how widespread it is when it is diagnosed. The cancer’s stage is one of the most important factors in choosing treatment options and predicting a patient’s outlook.

Liver cancer is staged based on the results of the physical exam, imaging tests (ultrasound, CT or MRI scan, etc.) and other tests, as well as by the results of surgery if it has been done.

There are several staging systems for liver cancer, and not all doctors use the same system.

The American Joint Committee on Cancer (AJCC) TNM system

A staging system is a standard way for the cancer care team to sum up information about how far a cancer has spread. Doctors use staging systems to get an idea about a patient’s prognosis (outlook) and to help determine the most appropriate treatment.

The TNM system for staging contains 3 key pieces of information:

• T describes the number and size of the primary tumor(s), measured in centimeters (cm), and whether the cancer has grown into nearby blood vessels or organs.
• N describes the extent of spread to nearby (regional) lymph nodes, which are bean-sized collections of immune system cells to which cancers often spread first.
• M indicates whether the cancer has metastasized (spread) to distant parts of the body.

Numbers or letters that appear after T, N, and M provide more details about each of these factors:

• The numbers 0 through 4 indicate increasing severity.
• The letter X means “cannot be assessed” because the information is not available.

T groups

TX: Primary tumor cannot be assessed

T0: No evidence of primary tumor

T1: A single tumor (any size) that hasn’t grown into blood vessels

T2: Either a single tumor (any size) that has grown into blood vessels, OR more than one tumor but no tumor is larger than 5 cm (about 2 inches) across

T3a: More than one tumor, with at least one tumor larger than 5 cm across

T3b: At least one tumor (any size) that has grown into a major branch of a large vein of the liver (the portal or hepatic vein)

T4: The tumor (any size) has grown into a nearby organ (other than the gallbladder), OR the tumor is growing into the thin layer of tissue covering the liver (called the visceral peritoneum)

N groups

NX: Regional (nearby) lymph nodes cannot be assessed.

N0: The cancer has not spread to the regional lymph nodes.

N1: The cancer has spread to the regional lymph nodes.

M groups

M0: The cancer has not spread to distant lymph nodes or other organs.

M1: The cancer has spread to distant lymph nodes or other organs. Liver cancer most often spreads to the lining of the belly (peritoneum), the lungs, and to bones.

Stages of liver cancer

Once the T, N, and M groups have been determined, they are then combined to give an overall stage, using Roman numerals I to IV (1 to 4).

Table 1. Liver cancer staging using the TNM classification

Stage	Stage grouping	Stage description
I	T1, N0, M0	There is a single tumor (any size) that has not grown into any blood vessels. The cancer has not spread to nearby lymph nodes or distant sites.
II	T2, N0, M0	Either there is a single tumor (any size) that has grown into blood vessels, OR there are several tumors, and all are 5 cm (2 inches) or less across. The cancer has not spread to nearby lymph nodes or distant sites.
IIIA	T3a, N0, M0	There is more than one tumor, and at least one is larger than 5 cm (2 inches) across. The cancer has not spread to nearby lymph nodes or distant sites.
IIIB	T3b, N0, M0	At least one tumor is growing into a branch of a major vein of the liver (portal vein or hepatic vein). The cancer has not spread to nearby lymph nodes or distant sites.
IIIC	T4, N0, M0	A tumor is growing into a nearby organ (other than the gallbladder), OR a tumor has grown into the outer covering of the liver. The cancer has not spread to nearby lymph nodes or distant sites.
IVA	Any T, N1, M0	Tumors in the liver can be any size or number and they may have grown into blood vessels or nearby organs. The cancer has spread to nearby lymph nodes. The cancer has not spread to distant sites.
IVB	Any T, Any N, M1	The cancer has spread to other parts of the body. (Tumors can be any size or number, and nearby lymph nodes may or may not be involved.)

[Source ²¹]

Other liver cancer staging systems

The staging systems for most types of cancer depend only on the extent of the cancer, but liver cancer is complicated by the fact that most patients have damage to the rest of their liver along with the cancer. This also affects treatment options and prognosis.

Although the TNM system defines the extent of liver cancer in some detail, it does not take liver function into account. Several other staging systems have been developed that include both of these factors:

• The Barcelona Clinic Liver Cancer (BCLC) system
• The Cancer of the Liver Italian Program (CLIP) system
• The Okuda system

These staging systems have not been compared against each other. Some are used more than others in different parts of the world, but at this time there is no single staging system that all doctors use. If you have questions about the stage of your cancer or which system your doctor uses, be sure to ask.

Child-Pugh score (cirrhosis staging system)

The Child-Pugh score is a measure of liver function, especially in people with cirrhosis. Many people with liver cancer also have cirrhosis, and in order to treat the cancer, doctors need to know how well the liver is working. This system looks at 5 factors, the first 3 of which are results of blood tests:

• Blood levels of bilirubin (the substance that can cause yellowing of the skin and eyes)
• Blood levels of albumin (a major protein normally made by the liver)
• The prothrombin time (measures how well the liver is making blood clotting factors)
• Whether there is fluid (ascites) in the abdomen
• Whether the liver disease is affecting brain function

Based on these factors, liver function is divided into 3 classes. If all these factors are normal, then liver function is called class A. Mild abnormalities are class B, and severe abnormalities are class C. People with liver cancer and class C cirrhosis are often too sick for surgery or other major cancer treatments.

The Child-Pugh score is actually part of the BCLC and CLIP staging systems mentioned previously.

Liver cancer classification

Formal staging systems (such as those described before) can often help doctors determine a patient’s prognosis (outlook). But for treatment purposes, doctors often classify liver cancers more simply, based on whether or not they can be entirely cut out (resected). Resectable is the medical term meaning “able to be removed by surgery.”

Potentially resectable or transplantable cancers

These cancers can be completely removed by surgery or treated with a liver transplant and the patient is healthy enough for surgery. This would include most stage I and some stage II cancers in the TNM system, in patients who do not have cirrhosis or other serious medical problems. Only a small number of patients with liver cancer have this type of tumor.

Unresectable liver cancers

Cancers that have not spread to the lymph nodes or distant organs but cannot be completely removed by surgery are classified as unresectable. This includes cancers that have spread throughout the liver or can’t be removed safely because they are close to the area where the liver meets the main arteries, veins, and bile ducts.

Inoperable with only local disease

The liver cancer is small enough and in the right place to be removed but you aren’t healthy enough for surgery. Often this is because the non-cancerous part of your liver is not healthy (because of cirrhosis, for example), and if the cancer is removed, there might not be enough liver tissue left for it to function properly. It could also mean that you have serious medical problems that make surgery unsafe.

Advanced (metastatic) liver cancers

Cancers that have spread to lymph nodes or other organs are classified as advanced. These would include stages IVA and IVB cancers in the TNM system. Most advanced liver cancers cannot be treated with surgery.

Liver Cancer Prognosis

The natural course of early tumors is poorly known because most hepatocellular carcinoma patients are treated. However, older reports have described 3-year survival rates of 13% to 21% without any specific treatment ²², ²³. At present, only 10% to 23% of patients with hepatocellular carcinoma may be surgical candidates for curative-intent treatment ²⁴, ²⁵. The 5-year overall survival rate for patients with early hepatocellular carcinoma who are undergoing liver transplant is 44% to 78%; and for patients undergoing a liver resection, the OS rate is 27% to 70% ²⁶.

Liver transplantation, surgical resection, and ablation offer high rates of complete responses and a potential for cure in patients with early hepatocellular carcinoma ⁷.

The natural course of advanced-stage hepatocellular carcinoma is better known. Untreated patients with advanced disease usually survive less than 6 months ²⁷. The survival rate of untreated patients in 25 randomized clinical trials ranged from 10% to 72% at 1 year and 8% to 50% at 2 years ²⁸.

Unlike most patients with solid tumors, the prognosis of patients with hepatocellular carcinoma is affected by the tumor stage at presentation and by the underlying liver function. The following prognostic factors guide the selection of treatment:

• Anatomic extension of the tumor (i.e., tumor size, number of lesions, presence of vascular invasion, and extrahepatic spread).
• Performance status.
• Functional hepatic reserve based on the Child-Pugh score ²⁹, ³⁰.

Liver cancer survival rates

Survival rates tell you what part of people with the same type and stage of cancer are still alive a certain amount of time (usually 5 years) after they were diagnosed. These numbers can’t tell you how long you will live, but they may help give you a better understanding about how likely it is that your treatment will be successful.

What is a 5-year liver cancer survival rate ?

Statistics on the outlook for a certain type and stage of cancer are often given as 5-year survival rates, but many people live longer – often much longer – than 5 years. The 5-year survival rate is the percentage of people who live at least 5 years after being diagnosed with cancer. For example, a 5-year survival rate of 50% means that an estimated 50 out of 100 people who have that cancer are still alive 5 years after being diagnosed. Keep in mind, however, that many of these people live much longer than 5 years after diagnosis.

But remember, the 5-year relative survival rates are estimates – your outlook can vary based on a number of factors specific to you.

Relative survival rates are a more accurate way to estimate the effect of cancer on survival. These rates compare people with cancer to people in the overall population. For example, if the 5-year relative survival rate for a specific type and stage of cancer is 50%, it means that people who have that cancer are, on average, about 50% as likely as people who don’t have that cancer to live for at least 5 years after being diagnosed.

But remember, survival rates are estimates – your outlook can vary based on a number of factors specific to you. Your doctor can tell you how these numbers apply to you, as he or she is familiar with your situation.

Cancer survival rates don’t tell the whole story

Survival rates are often based on previous outcomes of large numbers of people who had the disease, but they can’t predict what will happen in any particular person’s case. Your doctor can tell you how the numbers below may apply to you, as he or she is familiar with the aspects of your particular situation.

Survival rates for liver cancer

The numbers below come from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, and are based on patients who were diagnosed with liver cancer (hepatocellular type) between 2005 and 2011.

The SEER database does not divide liver cancer survival rates by AJCC TNM stages. Instead, it groups cancer cases into summary stages:

• Localized means the cancer is still confined to the liver, and includes stages I, II, and some stage III cancers. This includes a wide range of cancers, some of which are easier to treat than others. The 5-year relative survival rate for people with localized liver cancer is about 31%.

• Regional means the cancer has grown into nearby organs or has spread to nearby lymph nodes, and includes stages IIIC and IVA cancers. For regional stage liver cancer, the 5-year survival rate is about 11%.

• Distant means that the cancer has spread to distant organs or tissues and is the same as stage IVB. The 5-year relative survival rate for distant stage liver cancer is about 3%.

In general, survival rates are higher for people who can have surgery to remove their cancer, regardless of the stage. For example, studies have shown that patients with small, resectable tumors who do not have cirrhosis or other serious health problems are likely to do well if their cancers are removed. Their overall 5-year survival is over 50%. For people with early-stage liver cancers who have a liver transplant, the 5-year survival rate is in the range of 60% to 70%.

Liver cancer treatment

After liver cancer is diagnosed and staged, your cancer care team will discuss your treatment options with you.

In creating your treatment plan, important factors to consider include the stage (extent) of the cancer and the health of the rest of your liver. But you and your cancer care team will also want to take into account the possible side effects of treatment, your overall health, and the chances of curing the disease, extending life, or relieving symptoms. Based on these factors, your treatment options may include:

• Surgery (partial hepatectomy or liver transplant)
• Tumor ablation
• Tumor embolization
• Radiation therapy
• Targeted therapy
• Chemotherapy

Which doctors treat liver cancer ?

Depending on your situation, you may have different types of doctors on your treatment team. These doctors may include:

• A surgeon: a doctor who treats diseases with surgery.
• A radiation oncologist: a doctor who treats cancer with radiation therapy.
• A medical oncologist: a doctor who treats cancer with medicines such as chemotherapy.
• A gastroenterologist: a doctor who specializes in treating diseases of the digestive system, including the liver.

Many other specialists may be involved in your care as well, including nurse practitioners, nurses, nutrition specialists, social workers, and other health professionals.

Making treatment decisions

It is important to discuss all of your treatment options, including their goals and possible side effects, with your doctors to help make the decision that best fits your needs. Some important things to consider include:

• Your age and expected life span
• Any other serious health conditions you have
• The stage (extent) of your cancer
• Whether or not surgery can remove (resect) the cancer
• The likelihood that treatment will cure the cancer (or help in some other way)
• Your feelings about the possible side effects from treatment

You may feel that you must make a decision quickly, but it’s important to give yourself time to absorb the information you have just learned. It’s also very important to ask questions if there is anything you’re not sure about.

Getting a second opinion

If time allows, you may also want to get a second opinion from another doctor or medical team. This can give you more information and help you feel more certain about the treatment plan you choose. If you aren’t sure where to go for a second opinion, ask your doctor for help.

Thinking about taking part in a clinical trial

Clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to get state-of-the art cancer treatment. Sometimes they may be the only way to get access to newer treatments. They are also the best way for doctors to learn better methods to treat cancer. Still, they are not right for everyone.

If you would like to learn more about clinical trials that might be right for you, start by asking your doctor if your clinic or hospital conducts clinical trials.

Treatment of Liver Cancer, by Stage

Although the AJCC (TNM) staging system (see Liver Cancer Stages) is often used to describe the spread of a liver cancer precisely, doctors use a more practical system to determine treatment options. Liver cancers are categorized as: potentially resectable or transplantable, unresectable, inoperable with only local disease, and advanced.

Potentially resectable or transplantable liver cancers (stage I and some stage II tumors)

Potentially resectable: If your cancer is early stage and the rest of your liver is healthy, surgery (partial hepatectomy) may cure you. Only a small number of people with liver cancer are in this category. An important factor affecting outcome is the size of the tumor(s) and if nearby blood vessels are affected. Larger tumors or those that invade blood vessels are more likely to come back in the liver or spread elsewhere after surgery. The function of the rest of the liver and your general health are also important. For some people with early-stage liver cancer, a liver transplant could be another option.

Clinical trials are now looking at whether patients who have a partial hepatectomy will be helped by getting other treatments in addition to surgery. Some studies have found that using chemoembolization or other treatments along with surgery may help some patients live longer. Still, not all studies have found this, and more research is needed to know the value (if any) of adding other treatments to surgery.

Potentially transplantable: If your cancer is at an early stage, but the rest of your liver isn’t healthy, you may be able to be treated with a liver transplant. Liver transplant may also be an option if the tumor is in a part of the liver that makes it hard to remove (such as very close to a large blood vessel). Candidates for liver transplant might have to wait a long time for a liver to become available. While they are waiting, they are often given other treatments, such as ablation or embolization, to keep the cancer in check.

Unresectable liver cancers (some T1 to T4, N0, M0 tumors)

Unresectable cancers include cancers that haven’t yet spread to lymph nodes or distant sites, but can’t be removed safely by partial hepatectomy. This might be because:

• The tumor is too large to be removed safely
• The tumor is in a part of the liver that makes it hard to remove (such as very close to a large blood vessel)
• There are several tumors or the cancer has spread throughout the liver

Treatment options include ablation, embolization, or both for the liver tumor(s). Other options may include targeted therapy, chemotherapy (either systemic or by hepatic artery infusion), and/or radiation therapy. In some cases, treatment may shrink the tumor(s) enough so that surgery (partial hepatectomy or transplant) may become possible.

These treatments won’t cure the cancer, but they can reduce symptoms and may even help you live longer. Because these cancers can be hard to treat, clinical trials of newer treatments may offer a good option in many cases.

Inoperable liver cancers with only local disease

These cancers are small enough and in the right place to be removed but the patient isn’t healthy enough for surgery. Treatment options include ablation, embolization, or both for the liver tumor(s). Other options may include targeted therapy, chemotherapy (either systemic or by hepatic artery infusion), and/or radiation therapy.

Advanced (metastatic) liver cancers (includes all N1 or M1 tumors)

Advanced liver cancer has spread either to the lymph nodes or to other organs. Because these cancers are widespread, they cannot be treated with surgery.

If your liver is functioning well enough (Child-Pugh class A or B), the targeted therapy drug sorafenib (Nexavar) may help control the growth of the cancer for a time and may help you live longer. If this drug is no longer working, the targeted drug regorafenib (Stivarga) might be helpful.

As with localized unresectable liver cancer, clinical trials of targeted therapies, new approaches to chemotherapy (new drugs and ways to deliver chemotherapy), new forms of radiation therapy, and other new treatments may help you. These clinical trials are also important for improving the outcome for future patients.

Treatments such as radiation might also be used to help relieve pain and other symptoms. Please be sure to discuss any symptoms you have with your cancer team, so they can treat them effectively.

Recurrent liver cancer

Cancer that comes back after treatment is called recurrent. Recurrence can be local (in or near the same place it started) or distant (spread to organs such as the lungs or bone). Treatment of liver cancer that returns after initial therapy depends on many factors, including where it comes back, the type of initial treatment, and how well the liver is functioning. Patients with localized resectable disease that recurs in the liver might be eligible for further surgery or local treatments like ablation or embolization. If the cancer is widespread, targeted therapy or chemotherapy drugs may be options. Patients may also wish to ask their doctor whether a clinical trial may be right for them.

Treatment can also be given to relieve pain and other side effects. Please be sure to discuss any symptoms you have with your cancer care team, so they may be treated effectively.

Adding other treatments to surgery

An active area of research uses adjuvant therapies – treatments given right after surgery – to try to reduce the chances that the cancer will return. Most of the studies so far using chemotherapy or chemoembolization after surgery have not shown that they help people live longer. Research studies are also looking into newer drugs, like targeted therapy and may prove to be more effective. Some promising results have also been seen with radioembolization, but these need to be confirmed in larger studies. Another area of study has been the use of anti-viral therapy in people with liver cancer related to having viral hepatitis to see if it improves outcomes after surgery.

Doctors are also studying ways to make more liver cancers resectable by trying to shrink them before surgery. Studies are now looking at different types of neoadjuvant therapies (therapies given before surgery), including targeted therapy, chemotherapy, ablation, embolization, and radiation therapy. Early results have been promising but have only looked at small numbers of patients.

Considering complementary and alternative methods

You may hear about complementary or alternative methods that your doctor hasn’t mentioned to treat your cancer or relieve symptoms. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

Complementary methods refer to treatments that are used along with your regular medical care. Alternative treatments are used instead of a doctor’s medical treatment. Although some of these methods might be helpful in relieving symptoms or helping you feel better, many have not been proven to work. Some might even be dangerous.

As you consider your options, look for “red flags” that might suggest fraud.

• Does the method promise to cure all or most cancers?
• Are you told not to have regular medical treatments?
• Is the treatment a “secret” that requires you to visit certain providers or travel to another country?

Be sure to talk to your cancer care team about any method you are thinking about using. They can help you learn what is known (or not known) about the method, which can help you make an informed decision.

Choosing to stop treatment or choosing no treatment at all

For some people, when treatments have been tried and are no longer controlling the cancer, it could be time to weigh the benefits and risks of continuing to try new treatments. Whether or not you continue treatment, there are still things you can do to help maintain or improve your quality of life.

Some people, especially if the cancer is advanced, might not want to be treated at all. There are many reasons you might decide not to get cancer treatment, but it’s important to talk this through with your doctors before you make this decision. Remember that even if you choose not to treat the cancer, you can still get help for pain or other symptoms.

Help getting through treatment

Your cancer care team will be your first source of information and support, but there are other resources for help when you need it. Hospital- or clinic-based support services are an important part of your care. These might include nursing or social work services, financial aid, nutritional advice, rehab, or spiritual help.

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