close
liver cancer
Contents hide
Liver cancer
Liver cancer treatment

Liver cancer

Cancers that start in the cells of the liver are called liver cancer or primary liver cancer 1. Primary liver cancer is cancer that forms in the tissues of the liver. On the other hand, secondary liver cancer is when a cancer that started from another part of your body but spreads to the liver. Secondary liver cancers are also called liver metastases or metastatic liver cancer. This is different from having a cancer that first started in your liver (a primary liver cancer). In a primary liver cancer, the cancer is made up of liver cells (hepatocytes) that have become cancerous. This distinction is important because the type (origin) of cancer tells your doctor which type of treatment you need. So, for example a cancer that starts in the colon (bowel) may spread to the liver and is called colon (bowel) cancer with spread to the liver, not liver cancer. The cancer cells in the liver are the same type of cells that started in the colon (bowel) and it is treated as colon (bowel) cancer.

Most liver cancer is secondary liver cancer or metastatic liver cancer. And any cancer can spread to the liver.

The most common cancers that spread or metastasize to the liver are:

  • breast cancer
  • colon (bowel) cancer
  • lung cancer
  • pancreatic cancer
  • stomach cancer
  • ovarian cancer
  • neuroendocrine tumor (NET) cancers

Primary liver cancer, which starts in the liver, accounts for about 2% of cancers in the U.S., but up to half of all cancers in some developing countries 2. This is largely due to the prevalence of chronic viral B hepatitis and C hepatitis infections, which predisposes a person to liver cancer 3. In the U.S., primary liver cancer strikes twice as many men as women, at the average age of 67. Men have an incidence of 11.5 per 100,000 compared to 3.9 per 100,000 in women.

Several types of cancer can form in the liver. The most common type of liver cancer is hepatocellular carcinoma (HCC), which begins in the main type of liver cell (hepatocyte). Other types of liver cancer, such as intrahepatic cholangiocarcinoma and hepatoblastoma, are much less common.

The American Cancer Society estimates for liver cancer in the United States for 2022 are 4, 5:

  • New cases: About 41,260 new cases (28,600 in men and 12,660 in women) will be diagnosed.
  • Deaths: About 30,520 people (20,420 men and 10,100 women) will die of these cancers (liver and intrahepatic bile duct cancer).
  • 5-Year Relative Survival: 20.8%. Relative survival is an estimate of the percentage of patients who would be expected to survive the effects of their cancer. It excludes the risk of dying from other causes. Because survival statistics are based on large groups of people, they cannot be used to predict exactly what will happen to an individual patient. No two patients are entirely alike, and treatment and responses to treatment can vary greatly.
  • Liver and intrahepatic bile duct cancer deaths as a percentage of All Cancer Deaths: 5.0%.
  • Rate of New Cases and Deaths per 100,000: The rate of new cases of liver and intrahepatic bile duct cancer was 9.5 per 100,000 men and women per year. The death rate was 6.6 per 100,000 men and women per year. These rates are age-adjusted and based on 2015–2019 cases and 2016–2020 deaths.
  • Lifetime Risk of Developing Cancer: Approximately 1.1 percent of men and women will be diagnosed with liver and intrahepatic bile duct cancer at some point during their lifetime, based on 2017–2019 data.
  • In 2019, there were an estimated 100,476 people living with liver and intrahepatic bile duct cancer in the United States.

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.

Liver functions:

  • Your liver breaks down and stores many of the nutrients absorbed from the intestine that your body needs to function. Some nutrients must be changed (metabolized) in the liver before they can be used for energy or to build and repair body tissues.
  • Your liver makes most of the clotting factors that keep you from bleeding too much when you are cut or injured.
  • Your liver delivers bile into the intestines to help absorb nutrients (especially fats).
  • Your liver breaks down alcohol, drugs, and toxic wastes in the blood, which then pass from the body through urine and stool

Your liver lie under your right ribs just beneath your right lung. Your liver 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.

The 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).

Figure 1. Normal liver

liver

Figure 2. Liver anatomy

Liver anatomy

Figure 3. Liver lobule

liver hepatic lobules

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.

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 2022 are 4:

  • About 41,260 new cases (28,600 in men and 12,660 in women) will be diagnosed.
  • About 30,520 people (20,420 men and 10,100 women) will die of these cancers (liver and intrahepatic bile duct cancer).

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 4. In many of these countries liver cancer is the most common type of cancer. More than 700,000 people are diagnosed with liver 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.

What does the liver do?

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.

  • Stores nutrients. Two blood vessels supply your liver with blood. They are the hepatic artery and the hepatic portal vein. Just before it reaches the liver, the blood in the portal vein comes through the gut (digestive system). As it flows through, it picks up the carbohydrates, proteins, fats and vitamins. These are the nutrients that the digestive system breaks down from the food that you eat. The blood then carries these nutrients to the liver.
  • Converts fat to energy when the body needs it. Your liver uses chemicals to convert foods that you eat into energy. It does this with food containing carbohydrates and fat.
  • Makes bile. Your liver makes bile. This is a substance that helps the digestion and absorption of food. Bile is stored in a small sack below the liver called the gallbladder. The bile passes into the bowel through the bile duct. This is a tube that goes from the liver to the first part of the small bowel (duodenum).
  • Makes proteins. Your liver makes proteins including albumin. Albumin is a protein found in blood. It helps to keep the right balance of fluid between the body’s tissues and the bloodstream.
  • Helps to clot the blood. Your liver makes substances that help your blood to clot. These substances help to control bleeding when you cut yourself.
  • Makes substances the body needs. Your body makes substances that are essential for healthy bones and tissues. It also makes cholesterol, which is an important part of cell walls.
  • Breaks down harmful substances. Your liver breaks down harmful substances so that the body can get rid of them in your pee (urine) or poop (feces). This includes alcohol, many drugs, and waste products from normal body processes. If the liver is not working properly, harmful substances can build up and cause problems.

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 because they have cirrhosis (from any cause), hereditary hemochromatosis, 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 months. Ultrasound uses sound waves to take pictures of internal organs. In some studies, screening was linked to improved survival from liver cancer.

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

At this time, the American Cancer Society does not have recommendations for liver cancer screening in people who are at average risk 6. Screening means testing for cancer in people who have no symptoms or history of cancer. But testing might be recommended for some people at higher risk.

Types of Primary Liver Cancer

A cancer that starts in the liver is called primary liver cancer. The liver is made up of different types of cells.

The type of liver cancer you have depends on where it starts and the type of cell it starts in. Knowing which type of liver cancer you have helps your doctors decide what treatment you need. The different types of primary liver cancer are:

  • Hepatocellular carcinoma (HCC), this is the most common type of liver cancer
  • Fibrolamellar cancer, this is a rare subtype of hepatocellular carcinoma
  • Bile duct cancer also called cholangiocarcinoma, this can start in the bile ducts within or outside the liver
  • Angiosarcoma also called hemangiosarcoma, which starts in the blood vessels of the liver and is extremely rare
  • Hepatoblastoma a rare childhood cancer

If your cancer began somewhere else and then spread to the liver, then it’s called secondary liver cancer or metastatic liver cancer (see secondary liver cancer section below).

Hepatocellular carcinoma (hepatocellular cancer)

Hepatocellular carcinoma also called hepatoma or HCC, is the most common type of primary liver cancer in adults with about 90 percent of liver cancers in the United States 7, 8, 9, 10.

Hepatocellular carcinoma develops from the main liver cells called hepatocytes. It’s more common in people chronic liver diseases such as cirrhosis. Cirrhosis means scarring of the liver due to previous damage. For example, damage from the hepatitis B or hepatitis C virus, or long term alcohol drinking.

Hepatocellular carcinoma is more likely to develop in men than in women. It becomes more common as you get older.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor.

Risk factors for hepatocellular carcinoma include:

  • Having chronic hepatitis B (HBV) or chronic hepatitis C (HCV). The risk is even higher for people with both HBV and HCV, or people who have the hepatitis virus along with other risk factors listed below.
  • Cirrhosis, a disease where healthy liver tissue is replaced by scar tissue which blocks the flow of blood through the liver and keeps it from working as it should. Chronic alcoholism and chronic hepatitis infections are common causes of cirrhosis.
  • Heavy alcohol use.
  • Aflatoxin B1, poison from a fungus that can grow on foods.
  • Cigarette smoking.

Hepatocellular carcinoma develops from chronic liver disease caused by multiple risk factors 3. Hepatocellular carcinoma has a strong association with chronic hepatitis B and C virus (HBV and HCV) infections 3. Chronic hepatitis infections with other associated risk factors, including coinfection hepatitis D (HDV), alcohol consumption, cigarette smoking, may have a higher liver cancer risk 11, 12, 13. Patients with chronic hepatitis of any cause (e.g., hemochromatosis or alpha-1 antitrypsin deficiency) or cryptogenic cirrhosis have an increased risk of hepatocellular carcinoma. Environmental exposure to aflatoxin, contaminated water with blue-green algal toxin and betel nut contribute to hepatocellular carcinoma. Ethanol abuse and metabolic syndrome have been linked to liver cancer with persistent liver damage leading to steatosis, steatohepatitis, cirrhosis, and ultimately hepatocellular carcinoma. Protective factors of hepatocellular carcinoma have been associated with statins and coffee. Treatment of chronic hepatitis, metabolic syndrome, iron removal, alcohol cessation to prevent the development of cirrhosis may reduce Hepatocellular carcinoma development. Hepatitis B vaccination and hepatitis C virus (HCV) screening can reduce hepatocellular carcinoma incidence worldwide. Hepatocellular carcinoma surveillance guidelines are indicated for high-risk populations and vary per societies/institutions and usually recommend including ultrasonography, with or without alpha-fetoprotein (AFP), every 6 to 12 months 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.

Fibrolamellar carcinoma

Using a microscope, doctors can distinguish several subtypes of hepatocellular carcinoma. 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 14. Fibrolamellar carcinoma tends to develop in people in their 20’s or 30’s, most often seen in women younger than age 35. Often the rest of the liver is not diseased 15. Fibrolamellar carcinoma is not usually linked with cirrhosis or infection with hepatitis B or C. Some people with other types of liver cancer can have high levels of a chemical called alpha fetoprotein (AFP) in their blood. This is usually not the case for people with fibrolamellar carcinoma. Fibrolamellar carcinoma generally has a better outlook (prognosis) than other forms of hepatocellular carcinoma 15.

Cholangiocarcinoma (bile duct cancer)

About 10% to 20% of cancers that start in the liver are cholangiocarcinomas or bile duct cancer 14. Cholangio refers to the bile ducts, so cholangiocarcinoma is cancer of the bile ducts. The major bile ducts are tubes that connect the liver and gallbladder to the small bowel. The bile ducts carry bile, which is made by the liver. Bile helps to digest fats in food. Cholangiocarcinomas or bile duct cancers start in the cells that line the small bile ducts (tubes that carry bile to the gallbladder) within the liver are called intrahepatic cholangiocarcinoma. However, most cholangiocarcinomas actually start in the bile ducts outside the liver or extrahepatic cholangiocarcinoma.

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

Angiosarcoma (hemangiosarcoma)

Angiosarcoma is also known as hemangiosarcoma. It’s a type of cancer called a soft tissue sarcoma.

Angiosarcoma (hemangiosarcoma) begin in cells lining the blood vessels of the liver and is extremely rare. It is most often diagnosed in older people.

People who have been exposed to vinyl chloride or to thorium dioxide (Thorotrast) are more likely to develop these cancers 14. 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 14.

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 soft tissue sarcomas.

Hepatoblastoma

Hepatoblastoma is a very rare kind of primary liver cancer that develops in children, usually in those younger than 4 years old (most often diagnosed in children under 2) 14. The cells of hepatoblastoma are similar to fetal liver cells. About 2 out of 3 children with hepatoblastoma 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 or metastatic 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.

And any cancer can spread to the liver. The most common cancers that spread or metastasize to the liver are:

  • breast cancer
  • colon (bowel) cancer
  • lung cancer
  • pancreatic cancer
  • stomach cancer
  • ovarian cancer
  • neuroendocrine tumor (NET) cancers

In the United States and Europe, secondary (metastatic) liver tumors are more common than primary liver cancer 14. The opposite is true for many areas of Asia and Africa 14.

Most of the remaining content refers only to hepatocellular carcinoma.

Benign liver tumors

Most growths (tumors) in the liver are benign. Benign tumors or non cancerous growths aren’t cancer and won’t become cancerous (malignant) in the future. However, 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. Benign tumors do not usually need treatment. This can depend on the size of the tumor and whether it’s causing symptoms. If they need to be treated, the patient can usually be cured with surgery.

The most common types of benign tumors in the liver are:

  • Hemangioma
  • Hepatic adenoma
  • Focal nodular hyperplasia

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 with surgery.

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 lump 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 these 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.

Liver cancer causes

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.

Factors that increase the risk of primary liver cancer include:

  • Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Chronic infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV) increases your risk of liver cancer.
  • Cirrhosis. This progressive and irreversible condition causes scar tissue to form in your liver and increases your chances of developing liver cancer.
  • Certain inherited liver diseases. Liver diseases that can increase the risk of liver cancer include hemochromatosis and Wilson’s disease.
  • Diabetes. People with this blood sugar disorder have a greater risk of liver cancer than those who don’t have diabetes.
  • Nonalcoholic fatty liver disease (NAFLD). An accumulation of fat in the liver increases the risk of liver cancer.
  • Exposure to aflatoxins. Aflatoxins are poisons produced by molds that grow on crops that are stored poorly. Crops, such as grains and nuts, can become contaminated with aflatoxins, which can end up in foods made of these products.
  • Excessive alcohol consumption. Consuming more than a moderate amount of alcohol daily over many years can lead to irreversible liver damage and increase your risk of liver cancer.

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 increases your risk 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. People who think they may be at risk should discuss this with their doctor.

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.

Chronic viral hepatitis B or hepatitis C infection

Being infected with certain types of the hepatitis virus can cause hepatitis and increase the risk of liver cancer. 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 US, Europe and Japan, infection with hepatitis C is the more common cause of hepatocellular carcinoma 16, while in Asia and developing countries, hepatitis B is more common 17. 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 alcoholic drinks a day).

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 blood products are tested for these viruses. In developing countries, children sometimes contract hepatitis B infection from prolonged contact with family members who are infected.

Hepatitis B virus (HBV) is more likely to cause symptoms, such as a flu-like illness and jaundice (a yellowing of the eyes and skin). But most people recover completely from hepatitis B virus (HBV) 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 (HCV), on the other hand, is less likely to cause symptoms. But most people with hepatitis C virus (HCV) 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.

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) 18, 19.

In a single, prospective, population-based study that included 12,008 patients, the presence of anti-HCV positivity conferred a twenty fold increased risk of hepatocellular carcinoma compared with persons who were anti-HCV negative 20. Hepatocellular carcinoma may occur in hepatitis C virus-infected patients with bridging fibrosis, even in the absence of overt cirrhosis 21. 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 22.

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. This scarring can cause problems with the way the liver works. People with cirrhosis have an increased risk of liver cancer. Most (but not all) people who develop liver cancer (hepatocellular carcinoma or HCC) already have some evidence of cirrhosis.

Having cirrhosis increases your risk of getting liver cancer (hepatocellular carcinoma or HCC). The risk varies depending on the cause of the cirrhosis. Cirrhosis can be caused by:

  • long term infection with a virus such as hepatitis B or C
  • long term alcohol drinking
  • inherited diseases such as iron overload disorder (haemochromatosis) and alpha 1 antitrypsin deficiency
  • non-alcoholic fatty liver disease
  • primary biliary cirrhosis (PBC)

Most cirrhosis 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 (NAFLD)

Non-alcoholic fatty liver disease (NAFLD), a condition in which people who consume little or no alcohol develop a fatty liver, is common in obese people. Non alcoholic fatty liver disease (NAFLD) is a group of conditions including mild hepatic steatosis and non-alcoholic steatohepatitis (NASH). In these conditions fat builds up in the liver. The fat causes liver inflammation and liver damage, which might lead to cirrhosis. People with non-alcoholic steatohepatitis (NASH) might go on to develop cirrhosis. Non-alcoholic fatty liver disease (NAFLD) is common in people who have a group of symptoms (called metabolic syndrome). These include:

  • having extra weight around the waist
  • using insulin less effectively than normal
  • high blood pressure
  • high levels of fat in the blood

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 23.

Gallstones or gallbladder removal

People may have an increased risk of liver cancer if they:

  • have had gallstones before, or
  • had their gallbladder removed (cholecystectomy)

The increased risk may be due to raised pressure in the bile duct. This causes long term inflammation in the liver tissue.

Human immunodeficiency virus (HIV) or AIDS

Studies have shown that people with HIV or AIDS have an increased risk of liver cancer. This might be because they have low immunity, which means the body is less able to fight infection. So they are less likely to clear a hepatitis B or C infection, which can cause cirrhosis.

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 24.

Obesity

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

Diabetes and non alcoholic fatty liver disease (NAFLD) are more common in people who are overweight. So this may partly explain the link.

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 also be increased because people with type 2 diabetes tend to be overweight or obese, which in turn can cause liver problems. The liver cancer risk may also be increased in type 2 diabetes people who have other risk factors such as liver cirrhosis and hepatitis infection. Some treatments for diabetes such as metformin may reduce the risk of liver cancer.

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 25.

Hemochromatosis

Hemochromatosis is a significant risk factor for hepatocellular carcinoma and has an increased relative risk twenty times that of the normal population 26.

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

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 27.

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. They are usually caused by eating contaminated food or drinking contaminated water.

Smoking

Smoking increases your risk of many different cancers, including liver cancer. Former smokers have a lower risk than current smokers, but both groups have a higher risk than those who never smoked.

The risk of liver cancer is increased further if you smoke and drink a lot of alcohol. The risk might also be higher in people who smoke and have hepatitis B or C infection.

Betel quid

Betel quid is a combination of betel leaf, areca nut and slaked lime. It may also contain tobacco. There is some evidence that people who chew betel quid have an increased risk of liver cancer. There is some evidence that betel quid, even without the tobacco causes liver cancer. But more research is needed.

Getting older

Although liver cancer can happen at any age, it is most common in older people. Most people diagnosed are over the age of 60. The highest rates are in 85 to 89 year olds.

Family history

People with a family history of liver cancer may have an increased risk of developing it themselves. This might be due to genetic or shared environmental factors.

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 prevention

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 B and C 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 up to age 59, as well as older adults at risk for hepatitis B virus (HBV), get the hepatitis B vaccine to reduce the risk of hepatitis and liver cancer.

There is no vaccine for hepatitis C virus. Preventing hepatitis C virus (HCV) infection, as well as hepatitis B virus (HBV) 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
  • You might have been exposed to Hepatitis C in the last 6 months through sex or sharing needles during drug use

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.

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 28:

  • 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 (ascites)
  • Itching
  • Yellowing of the skin and eyes (jaundice)
  • White, chalky stools

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.

Liver cancer diagnosis

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.

Tests and procedures used to diagnose liver cancer include:

  • Blood tests. Blood tests may reveal liver function abnormalities.
  • Imaging tests. Your doctor may recommend imaging tests, such as an ultrasound, CT and MRI.
  • Removing a sample of liver tissue (liver biopsy) for testing. Sometimes it’s necessary to remove a piece of liver tissue for laboratory testing in order to make a definitive diagnosis of liver cancer. During a liver biopsy, your doctor inserts a thin needle through your skin and into your liver to obtain a tissue sample. In the lab, doctors examine the tissue under a microscope to look for cancer cells. Liver biopsy carries a risk of bleeding, bruising and infection.

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

Once liver cancer is diagnosed, your doctor will work to determine the extent (stage) of the liver cancer. Staging tests help determine the size and location of cancer and whether it has spread. Imaging tests used to stage liver cancer include CTs, MRIs and bone scans 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. For example, one method uses Roman numerals I through IV, and another uses letters A through D. Your doctor uses your cancer’s stage to determine your treatment options and your prognosis. As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means cancer has spread more. Although each person’s cancer experience is unique, cancers with similar stages tend to have a similar outlook and are often treated in much the same way.

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:

  • The extent (size) of the tumor (T): How large has the cancer grown? Is there more than one tumor in the liver? Has the cancer reached nearby structures like the veins in the liver?
  • The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes?
  • The spread (metastasis) to distant sites (M): Has the cancer spread to distant lymph nodes or distant organs such as the bones or lungs?

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 AJCC (American Joint Committee on Cancer) TNM system classification

AJCC StageStage groupingStage description*
IAT1a
N0
M0
A single tumor 2 cm (4/5 inch) or smaller that hasn’t grown into blood vessels (T1a).
It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
IBT1b
N0
M0
A single tumor larger than 2cm (4/5 inch) that hasn’t grown into blood vessels (T1b).
The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0).
IIT2
N0
M0
Either a single tumor larger than 2 cm (4/5 inch) that has grown into blood vessels, OR more than one tumor but none larger than 5 cm (about 2 inches) across (T2).
It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
IIIAT3
N0
M0
More than one tumor, with at least one tumor larger than 5 cm across (T3).
It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
IIIBT4
N0
M0
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).
It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
IVAAny T
N1
M0
A single tumor or multiple tumors of any size (Any T) that has spread to nearby lymph nodes (N1) but not to distant sites (M0).
IVBAny T
Any N
M1
A single tumor or multiple tumors of any size (any T).
It might or might not have spread to nearby lymph nodes (any N).
It has spread to distant organs such as the bones or lungs (M1).

Footnotes: * The following additional categories are not listed on the table above:

  • TX: Main tumor cannot be assessed due to lack of information.
  • T0: No evidence of a primary tumor.
  • NX: Regional lymph nodes cannot be assessed due to lack of information.
[Source 29 ]

Stage 1 liver cancer

Stage 1 liver cancer has not spread to the lymph nodes or anywhere else in the body.

Stage 1 liver cancer is divided into stage 1A and stage 1B.

  • Stage 1A means there is a single tumor in the liver that is 2cm or less, and it has not grown into the blood vessels.
  • Stage 1B means there is a single tumor that is more than 2cm, and it has not grown into the blood vessels.

Figure 4. Stage 1 liver cancer

Stage 1 liver cancer

Stage 2 liver cancer

Stage 2 liver cancer means that there is a single tumor that is more than 2 cm, and it has grown into blood vessels of the liver. Or it means that there are several tumours in the liver and they are all less than 5cm.

Stage 2 liver cancer has not spread to the lymph nodes or other areas of the body.

Figure 5. Stage 2 liver cancer

Stage 2 liver cancer

Stage 3 liver cancer

Stage 3 liver cancer is divided into 2 further stages – stage 3A and 3B.

  • Stage 3A liver cancer. There is more than one tumor, and at least one of them is larger than 5cm. At this stage the cancer has not spread to the lymph nodes or any other part of the body.
  • Stage 3B liver cancer. The cancer has grown into one of the main blood vessels of the liver (the portal vein or hepatic vein). Or the cancer has spread into organs close to the liver (not including the gallbladder), or through the lining that wraps around the internal organs of the abdomen (the visceral peritoneum). It has not spread to the lymph nodes or any other part of the body.

Figure 6. Stage 3A liver cancer

Stage 3A liver cancer

Figure 7. Stage 3B liver cancer

Stage 3B liver cancer

Stage 4 liver cancer

Stage 4 liver cancer is divided into 2 further stages – stage 4A and 4B.

Knowing the stage of your cancer helps you and your doctors plan the best treatment for you.

  • Stage 4A liver cancer. The cancer is any size and there may be more than one tumor. It may have grown into blood vessels or the organs around the liver. It has spread to lymph nodes but not to other parts of the body.
  • Stage 4B liver cancer. The cancer is any size and there may be more than one tumor. It may have grown into blood vessels or the organs around the liver. It may or may not have spread into lymph nodes, but has spread to another part of the body such as the lungs or bones.

Figure 8. Stage 4A liver cancer

Stage 4A liver cancer

Figure 9. Stage 4B liver cancer

Stage 4B liver cancer

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 Barcelona Clinic Liver Cancer (BCLC) system looks at all of the following:
    • the number and size of tumours in your liver
    • your general health and fitness – this is called your performance status (PS)
    • how well your liver is working (liver function) using a system called the Child-Pugh score (cirrhosis staging 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:

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

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 Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) staging systems mentioned previously.

The Barcelona Clinic Liver Cancer (BCLC) staging system

Performance status (PS) is a scale to grade how well you are. The Barcelona Clinic Liver Cancer (BCLC) staging system uses the Eastern Cooperative Oncology Group (ECOG) scale:

  • PS 0 – you are fully active, more or less as you were before your illness
  • PS 1 – you can’t carry out heavy physical work, but can do anything else
  • PS 2 – you are up and about more than half the day. You can look after yourself but can’t work
  • PS 3 – you are in bed or a chair for more than half the day. You need help to look after yourself
  • PS 4 – you are in bed or a chair all the time and need complete care

There are 5 stages to the Barcelona Clinic Liver Cancer (BCLC) staging system:

  • Stage 0 (Very early stage). This means the tumour is less than 2cm, you feel well (PS 0) and your liver is working normally (Child-Pugh A).
  • Stage A (Early stage). This means there is a single tumour of any size, or up to 3 tumours all less than 3 cm. You feel well and are active (PS 0), and your liver is working well (Child-Pugh A or B).
  • Stage B (Intermediate Stage). This means there are many tumours in the liver, but you feel well (PS 0) and your liver is working well (Child-Pugh A or B).
  • Stage C (Advanced stage). This means the cancer has spread into the blood vessels, lymph nodes or other body organs. Or you do not feel well and are less active (PS 1 or 2). Your liver is still working well. (Child-Pugh A or B).
  • Stage D (End-stage). This means you have severe liver damage (Child-Pugh C), or you are not well and need help to look after yourself (PS 3 or 4).

Liver cancer classification

Formal staging systems (such as those described above) 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

If the patient is healthy enough for surgery, these cancers can be completely removed by surgery or treated with a liver transplant. 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 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 healthy 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 treatment

Treatments for primary liver cancer depend on the extent (stage) of the disease as well as your age, overall health and personal preferences. 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).
    • A partial hepatectomy (surgery to remove the part of the liver where cancer is found) may be done. A wedge of tissue, an entire lobe, or a larger part of the liver, along with some of the healthy tissue around it is removed. The remaining liver tissue takes over the functions of the liver and may regrow.
    • A liver transplant, the entire liver is removed and replaced with a healthy donated liver. A liver transplant may be done when the disease is in the liver only and a donated liver can be found. If the patient has to wait for a donated liver, other treatment is given as needed.
  • Tumor ablation. Ablation therapy removes or destroys tissue. Different types of ablation therapy are used for liver cancer:
    • Radiofrequency ablation (RFA): Special needles are inserted directly through the skin or through an incision in the abdomen to reach the tumor. High-energy radio waves heat the needles and tumor which kills cancer cells.
    • Microwave ablation (MWA): The tumor is exposed to high temperatures created by microwaves. This can damage and kill cancer cells or make them more sensitive to the effects of radiation and certain anticancer drugs.
    • Percutaneous ethanol injection (PEI): A small needle is used to inject ethanol (pure alcohol) directly into a tumor to kill cancer cells. Several treatments may be needed. Usually local anesthesia is used, but if the patient has many tumors in the liver, general anesthesia may be used.
    • Cryoablation (cryotherapy): An instrument is used to freeze and destroy cancer cells. This type of treatment is also called cryotherapy and cryosurgery. The doctor may use ultrasound to guide the instrument.
    • Electroporation therapy: Electrical pulses are sent through an electrode placed in a tumor to kill cancer cells. Electroporation therapy is being studied in clinical trials.
  • Tumor embolization. There are two main types of embolization therapy:
    • Transarterial embolization (TAE): A small incision (cut) is made in the inner thigh and a catheter (thin, flexible tube) is inserted and threaded up into the hepatic artery. Once the catheter is in place, a substance that blocks the hepatic artery and stops blood flow to the tumor is injected.
    • Transarterial chemoembolization (TACE): This procedure is like transarterial embolization (TAE) except an anticancer drug is also given. The procedure can be done by attaching the anticancer drug to small beads that are injected into the hepatic artery or by injecting the anticancer drug through the catheter into the hepatic artery and then injecting the substance to block the hepatic artery. Most of the anticancer drug is trapped near the tumor and only a small amount of the drug reaches other parts of the body. This type of treatment is also called chemoembolization.
  • Radiation therapy. External radiation therapy (EBRT) uses a machine outside the body to send high-energy x-rays or other types of radiation toward the area of the body with cancer. This kills cancer cells or keeps them from growing. Certain ways of giving external radiation therapy can help keep radiation from damaging nearby healthy tissue:
    • Conformal radiation therapy: Conformal radiation therapy uses a computer to make a 3-dimensional, or 3-D, picture of the tumor and shapes the radiation beams to fit the tumor. This allows a high dose of radiation to reach the tumor and causes less damage to nearby healthy tissue.
    • Stereotactic body radiation therapy: Stereotactic body radiation therapy uses special equipment to place the patient in the same position for each radiation treatment. Once a day for several days, a radiation machine aims a larger than usual dose of radiation directly at the tumor. By having the patient in the same position for each treatment, there is less damage to nearby healthy tissue. This procedure is also called stereotactic external-beam radiation therapy and stereotaxic radiation therapy.
    • Proton beam radiation therapy: Proton beam radiation therapy is a type of high-energy, external radiation therapy that uses streams of protons (tiny particles with a positive charge) to kill tumor cells. This type of treatment can lower the amount of radiation damage to healthy tissue near a tumor.
  • Targeted drug therapy. Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do. Targeted therapies used to treat advanced liver cancer include the following:
    • bevacizumab
    • cabozantinib
    • lenvatinib
    • ramucirumab
    • regorafenibsorafenib
  • Immunotherapy. Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. Immune checkpoint inhibitors are a type of immunotherapy. Immune checkpoint inhibitors that may be used to treat liver cancer include the following:
    • atezolizumab with the targeted therapy bevacizumab
    • nivolumab with ipilimumab
    • pembrolizumab
  • Chemotherapy (chemo). Chemotherapy is treatment with drugs to destroy cancer cells. Unfortunately, most chemo drugs do not have a great effect on liver cancer. The most common chemotherapy drugs for treating liver cancer include:
    • Gemcitabine (Gemzar)
    • Oxaliplatin (Eloxatin)
    • Cisplatin
    • Doxorubicin (pegylated liposomal doxorubicin)
    • 5-fluorouracil (5-FU)
    • Capecitabine (Xeloda)
    • Mitoxantrone (Novantrone)

For cancer that is only in the liver, it might be possible to remove the tumor with surgery. This might be surgery to remove part of your liver (liver resection) or a liver transplant.

You might have a local treatment into your liver if you can’t have surgery such as:

  • radiofrequency ablation (RFA) or microwave ablation (MWA)
  • chemoembolisation (TACE)
  • selective internal radiotherapy (SIRT)

For liver cancer that has spread you might have targeted or immunotherapy drugs, such as atezolizumab with bevacuzimab or sorafenib.

If you have severe liver damage, you are usually too unwell to have treatment for your cancer. But your doctor will give you different treatments to help control your symptoms.

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.
  • An interventional radiologist: A doctor who specializes in procedures such as ablations and embolizations.

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.

Surgery for liver cancer

The best option to cure liver cancer is with either surgical resection (removal of the tumor with surgery) or a liver transplant. If all cancer in the liver is completely removed, you will have the best outlook. Small liver cancers may also be cured with other types of treatment such as ablation or radiation.

Partial hepatectomy

Partial hepatectomy is surgery to remove part of the liver. Only people with good liver function who are healthy enough for surgery and who have a single tumor that has not grown into blood vessels can have this operation.

Imaging tests, such as CT or MRI with angiography are done first to see if the cancer can be removed completely. Still, sometimes during surgery the cancer is found to be too large or has spread too far to be removed, and the surgery that has been planned cannot be done.

Most patients with liver cancer in the United States also have cirrhosis. In someone with severe cirrhosis, removing even a small amount of liver tissue at the edges of a cancer might not leave enough liver behind to perform important functions.

People with cirrhosis are typically eligible for surgery if there is only one tumor (that has not grown into blood vessels) and they will still have a reasonable amount (at least 30%) of liver function left once the tumor is removed. Doctors often assess this function by assigning a Child-Pugh score, which is a measure of cirrhosis based on certain lab tests and symptoms.

Patients in Child-Pugh class A are most likely to have enough liver function to have surgery. Patients in class B are less likely to be able to have surgery. Surgery is not typically an option for patients in class C.

Partial hepatectomy possible risks and side effects

Liver resection is a major, serious operation that should only be done by skilled and experienced surgeons. Because people with liver cancer usually have other liver problems besides the cancer, surgeons have to remove enough of the liver to try to get all of the cancer, but also leave enough behind for the liver to function.

  • Bleeding: A lot of blood passes through the liver, and bleeding after surgery is a major concern. Also, the liver normally makes substances that help the blood clot. Damage to the liver (both before the surgery and during the surgery) can add to potential bleeding problems.
  • Infection
  • Complications from anesthesia
  • Blood clots
  • Pneumonia
  • New liver cancer: Because the remaining liver still has the underlying disease that led to the cancer, sometimes a new liver cancer can develop afterward.

Liver transplant

When it is available, a liver transplant may be the best option for some people with liver cancer. Liver transplants can be an option for those with tumors that cannot be removed with surgery, either because of the location of the tumors or because the liver has too much disease for the patient to tolerate removing part of it. In general, a transplant is used to treat patients with small tumors (either 1 tumor smaller than 5 cm across or 2 to 3 tumors no larger than 3 cm) that have not grown into nearby blood vessels. It can also rarely be an option for patients with resectable cancers (cancers that can be removed completely). With a transplant, not only is the risk of a second new liver cancer greatly reduced, but the new liver will function normally.

According to the Organ Procurement and Transplantation Network, about 1,000 liver transplants were done in people with liver cancer in the United States in 2016, the last year for which numbers are available. Unfortunately, the opportunities for liver transplants are limited. Only about 8,400 livers are available for transplant each year, and most of these are used for patients with diseases other than liver cancer. Increasing awareness about the importance of organ donation is an essential public health goal that could make this treatment available to more patients with liver cancer and other serious liver diseases.

Most livers used for transplants come from people who have just died. But some patients receive part of a liver from a living donor (usually a close relative) for transplant. The liver can regenerate some of its lost function over time if part of it is removed. Still, the surgery does carry some risks for the donor. About 370 living donor liver transplants are done in the United States each year. Only a small number of them are for patients with liver cancer.

People needing a transplant must wait until a liver is available, which can take too long for some people with liver cancer. In many cases a person may get other treatments, such as embolization or ablation, while waiting for a liver transplant. Or doctors may suggest surgery or other treatments first and then a transplant if the cancer comes back.

Liver transplant possible risks and side effects

Like partial hepatectomy, a liver transplant is a major operation with serious risks and should only be done by skilled and experienced surgeons. Possible risks include:

  • Bleeding
  • Infection: People who get a liver transplant are given drugs to help suppress their immune systems to prevent their bodies from rejecting the new organ. These drugs have their own risks and side effects, especially the risk of getting serious infections. By suppressing the immune system, these drugs might also allow any liver cancer that had spread outside of the liver to grow even faster than before. Some of the drugs used to prevent rejection can also cause high blood pressure, high cholesterol, and diabetes; can weaken the bones and kidneys; and can even lead to a new cancer.
  • Blood clots
  • Complications from anesthesia
  • Rejection of new liver: After a liver transplant, regular blood tests are done to check for signs of the body rejecting the new liver. Sometimes liver biopsies are also taken to see if rejection is happening and if changes are needed in the drugs that prevent rejection.

Ablation for liver cancer

Ablation is treatment that destroys liver tumors without removing them. These techniques can be used in patients with a few small tumors and when surgery is not a good option (often because of poor health or reduced liver function). They are less likely to cure the cancer than surgery, but they can still be very helpful for some people. These treatments are also sometimes used in patients waiting for a liver transplant.

Ablation is best used for tumors no larger than 3 cm across (a little over an inch). For slightly larger tumors (1 to 2 inches, or 3 to 5 cm across), it may be used along with embolization. Because ablation often destroys some of the normal tissue around the tumor, it might not be a good choice for treating tumors near major blood vessels, the diaphragm, or major bile ducts.

People getting this type of treatment typically do not need to stay in a hospital. Often, ablation can be done without surgery by inserting a needle or probe into the tumor through the skin. The needle or probe is guided into place with ultrasound or CT scan. Sometimes, though, to be sure the treatment is aimed at the right place, the ablation may be done in the operating room under general anesthesia (you are asleep) and may need an incision (cut) like the one for a partial hepatectomy .

Possible side effects after ablation therapy include abdominal pain, infection in the liver, fever and abnormal liver tests. Serious complications are uncommon, but they are possible.

Radiofrequency ablation (RFA)

Radiofrequency ablation is one of the most common ablation methods for small tumors. It uses high-energy radio waves. The doctor inserts a thin, needle-like probe into the tumor through the skin. A high-frequency current is then passed through the tip of the probe, which heats the tumor and destroys the cancer cells.

Microwave ablation (MWA)

Microwave ablation uses the energy from electromagnetic waves to heat and destroy the tumor using a probe.

Cryoablation (cryotherapy)

Cryoablation destroys a tumor by freezing it using a thin metal probe. The probe is guided into the tumor and then very cold gasses are passed through the probe to freeze the tumor which causes the cancer cells to die.

Ethanol (alcohol) ablation

Ethanol (alcohol) ablation is also known as percutaneous ethanol injection (PEI). In this procedure, concentrated alcohol is injected directly into the tumor to damage cancer cells. Sometimes multiple treatments of alcohol ablation may be needed.

Embolization therapy for liver cancer

Embolization is a procedure that injects substances directly into an artery in the liver to block or reduce the blood flow to a tumor in the liver. The liver is special in that it has 2 blood supplies. Most normal liver cells are fed by the portal vein, whereas a cancer in the liver is mainly fed by the hepatic artery. Blocking the part of the hepatic artery that feeds the tumor helps kill off the cancer cells, but it leaves most of the healthy liver cells unharmed because they get their blood supply from the portal vein.

Embolization is an option for some patients with tumors that cannot be removed by surgery. It can be used for people with tumors that are too large to be treated with ablation (usually larger than 5 cm across) and who also have adequate liver function. It can also be used with ablation. Embolization can reduce some of the blood supply to the normal liver tissue, so it may not be a good option for some patients whose liver has been damaged by diseases such as hepatitis or cirrhosis. It isn’t yet clear which type of embolization has a better long-term outcome.

People getting embolization treatment typically do not stay in the hospital overnight.

Possible complications after embolization include:

  • Abdominal pain
  • Fever
  • Nausea
  • Infection in the liver
  • Blood clots in the main blood vessels of the liver

Sometimes, it can take 4-6 weeks to fully recover from the procedure. Because healthy liver tissue can be affected, there is a risk that liver function will get worse after embolization. This risk is higher if a large branch of the hepatic artery is embolized. Serious complications are not common, but they are possible.

Trans-arterial embolization (TAE)

During trans-arterial embolization a catheter (a thin, flexible tube) is put into an artery in the inner thigh through a small cut and eased up into the hepatic artery in the liver. A dye is usually injected into the bloodstream to help the doctor watch the path of the catheter. Once the catheter is in place, small particles are injected into the artery to plug it up, blocking oxygen and key nutrients from the tumor.

Trans-arterial chemoembolization (TACE)

Trans-arterial chemoembolization is usually the first type of embolization used for large liver cancers that cannot be treated with surgery or ablation. It combines embolization with chemotherapy (chemo). Most often, this is done by giving chemotherapy through the catheter directly into the artery, then plugging up the artery, so the chemo can stay close to the tumor.

Drug-eluting bead chemoembolization (DEB-TACE)

Drug-eluting bead chemoembolization combines TACE embolization with drug-eluting beads (tiny beads that contain a chemotherapy drug). The procedure is essentially the same as trans-arterial chemoembolization (TACE) except that the artery is blocked after drug-eluting beads are injected. Because the chemo is physically close to the cancer and because the drug-eluting beads slowly release the chemo, the cancer cells are more likely to be damaged and die. The most common chemo drugs used for TACE or DEB-TACE are mitomycin C, cisplatin, and doxorubicin.

Radioembolization (RE)

Radioembolization combines embolization with radiation therapy. This is done by injecting small beads (called microspheres) that have a radioactive isotope (yttrium-90 or Y-90) attached to them into the hepatic artery. Once infused, the beads lodge in the blood vessels near the tumor, where they give off small amounts of radiation to the tumor site for several days. The radiation travels a very short distance, so its effects are limited mainly to the tumor.

Radiation therapy for liver cancer

Radiation therapy uses high-energy rays (or particles) to kill cancer cells. It may not be a good option for some patients whose liver has been greatly damaged by diseases such as hepatitis or cirrhosis.

Radiation can be helpful in treating:

Liver cancer that cannot be removed by surgery
Liver cancer that cannot be treated with ablation or embolization or did not respond well to those treatments
Liver cancer that has spread to other areas such as the brain or bones
People with pain because of large liver cancers
People with a tumor thrombus (a collection of liver cancer cells) blocking the portal vein.

Some of the more common side effects of radiation therapy include:

  • Skin changes in areas getting radiation, ranging from redness to blistering and peeling
  • Nausea and vomiting
  • Fatigue
  • Diarrhea
  • Loss of appetite

These effects typically go away within a few weeks after treatment ends.

A more serious side effect of radiation therapy to the liver is radiation-induced liver disease (RILD). It commonly happens 3 to 4 months after treatment and usually only lasts a set time, but can be fatal in some instances. Signs and symptoms seen with radiation-induced liver disease (RILD) can include abnormal blood liver tests, an enlarged liver and spleen, ascites (fluid build up in the abdomen), and jaundice. Ask your doctor what side effects to expect and how to prevent or relieve them.

External beam radiation therapy (EBRT)

External beam radiation therapy (EBRT) focuses radiation from a source outside of the body on the cancer. Getting radiation therapy is much like getting an x-ray, but the radiation is stronger. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time – getting you into place for treatment – usually takes longer. Most often, EBRT treatments are small doses of radiation given 5 days a week for several weeks.

Although liver cancer cells are sensitive to radiation, much care is taken when planning the treatment to avoid damaging normal liver tissue as much as possible. Newer radiation techniques, such as stereotactic body radiation therapy (SBRT), help doctors target liver tumors while reducing the radiation to nearby healthy tissues. This makes it more effective and reduces side effects. SBRT allows treatment to be completed in a short-time compared to external beam radiation therapy (EBRT). It uses very focused beams of high-dose radiation given on one or a few days. Beams are aimed at the tumor from many different angles. To focus the radiation precisely, the person is put in a specially designed body frame for each treatment. This type of radiation may be used in people with small cancers who are waiting for a liver transplant.

Radioembolization

Radioembolization combines embolization with radiation therapy. This is done by injecting small beads (called microspheres) that have a radioactive isotope (yttrium-90 or Y-90) attached to them into the hepatic artery. Once infused, the beads lodge in the blood vessels near the tumor, where they give off small amounts of radiation to the tumor site for several days. The radiation travels a very short distance, so its effects are limited mainly to the tumor.

Targeted drug therapy for liver cancer

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. You might also hear some targeted drugs called biological therapies. Other targeted drugs help the body’s immune system to attack the cancer. So some of these drugs are also called immunotherapies.

As researchers learn more about the changes in cells that cause cancer, they have been able to develop newer drugs that specifically target these changes. Targeted drugs work differently from standard chemotherapy drugs and often have different side effects.

Like chemotherapy, these drugs enter the bloodstream and reach almost all areas of the body, which makes them potentially useful against cancers that have spread to distant parts of the body. Because standard chemo is not very effective in most patients with liver cancer, doctors are focusing more on using targeted therapies.

Kinase inhibitors

Kinases are proteins on or near the surface of a cell that carry important signals to the cell’s control center. Many of the targeted drugs used to treat liver cancer are kinase inhibitors. These drugs block several kinase proteins, which normally help tumor cells grow in one of two ways:

  • Some kinases help tumor cells grow directly.
  • Some kinases help tumors form the new blood vessels they need in order to get bigger (a process called angiogenesis).

Blocking these proteins can often help stop the growth of the cancer.

Common side effects of kinase inhibitors can include fatigue, loss of appetite, hand-foot syndrome (redness and irritation of the hands and feet), high blood pressure, weight loss, diarrhea, and abdominal (belly) pain.

Less common but more serious side effects can include problems with blood flow to the heart, bleeding, abnormal thyroid tests, and perforations (holes) in the stomach or intestines.

Sorafenib (Nexavar) and lenvatinib (Lenvima)

One of these drugs can be used as the first treatment for liver cancer if it cannot be treated by surgery or if it has spread to other organs.

Sorafenib is a pill taken twice daily. Lenvatinib is a pill that is taken once a day.

Sorafenib may work better in people with liver cancer caused by hepatitis C.

Regorafenib (Stivarga) and cabozantinib (Cabometyx)

These drugs can be used to treat advanced liver cancer, typically if other treatments are no longer helpful.

Regorafenib is a pill, typically taken once a day for 3 weeks, followed by a week off. Cabozantinib is a pill taken once a day.

Monoclonal antibodies

Monoclonal antibodies are man-made versions of immune system proteins (antibodies) that are designed to attach to a specific target. The monoclonal antibodies used to treat liver cancer affect a tumor’s ability to form new blood vessels, which it needs to grow beyond a certain size. This new blood vessel growth is called angiogenesis, so these drugs are often referred to angiogenesis inhibitors.

Common side effects of angiogenesis inhibitors can include:

  • High blood pressure
  • Tiredness (fatigue)
  • Bleeding
  • Low white blood cell counts (with increased risk of infections)
  • Headaches
  • Mouth sores
  • Loss of appetite
  • Diarrhea

Rare but possibly serious side effects can include blood clots, severe bleeding, holes (called perforations) in the stomach or intestines, heart problems, and slow wound healing.

Bevacizumab (Avastin)

Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein that helps new blood vessels to form. This drug can be used along with the immunotherapy drug atezolizumab (Tecentriq) as the first treatment for liver cancer that cannot be treated by surgery or that has spread to other organs.

Bevacizumab is given as an infusion into a vein (IV), typically once every 3 weeks.

Ramucirumab (Cyramza)

Ramucirumab is a monoclonal antibody that targets a VEGF receptor (VEGFR) protein on cells, which can help stop the formation of new blood vessels. This drug can be used to treat advanced liver cancer, typically after another treatment stops working.

Ramucirumab is given as an infusion into a vein (IV), usually once every 2 weeks.

Immunotherapy for liver cancer

Immunotherapy is the use of medicines that help a person’s own immune system find and destroy cancer cells. It can be used to treat some people with liver cancer.

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoints” – proteins on immune cells that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Newer drugs that target these checkpoints hold a lot of promise as liver cancer treatments.

Possible side effects of checkpoint inhibitors can include:

  • Feeling tired or weak
  • Fever
  • Cough
  • Nausea
  • Itching
  • Skin rash
  • Loss of appetite
  • Muscle or joint pain
  • Constipation or diarrhea

Other, more serious side effects occur less often:

  • Infusion reactions: Some people might have an infusion reaction while getting these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting these drugs.
  • Autoimmune reactions: These drugs work by basically removing one of the safeguards on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, skin, or other organs.

Serious side effects seem to occur more often with ipilimumab than with the PD-1 and PD-L1 inhibitors.

It’s very important to report any new side effects to your health care team promptly. If serious side effects do occur, treatment may need to be stopped and you may get high doses of corticosteroids to suppress your immune system.

PD-1 and PD-L1 inhibitors

PD-1 is a checkpoint protein on immune cells called T cells. When PD-1 attaches to PD-L1, a protein on other cells in the body, it acts as a type of “off switch” that basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them hide from an immune attack. Drugs that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells.

Atezolizumab (Tecentriq) and durvalumab (Imfinzi) target the PD-L1 protein. Blocking this protein can help boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

Atezolizumab can be used along with the targeted drug bevacizumab (Avastin) as the first treatment for liver cancer that cannot be treated by surgery or that has spread to other organs.

Durvalumab can be used with another immunotherapy drug tremelimumab (Imjudo) as the first treatment for liver cancer that cannot be removed with surgery.

These drugs are given as an infusion into a vein (IV), typically once every 2, 3, or 4 weeks.

Pembrolizumab (Keytruda) and nivolumab (Opdivo) are drugs that target PD-1, which can help boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

These drugs can be used in people with advanced liver cancer who have previously been treated (such as with the targeted drug sorafenib [Nexavar]). Pembrolizumab can be used by itself, while nivolumab is typically used along with ipilimumab (see below).

These drugs are given as an intravenous (IV) infusion, typically every 2, 3, 4, or 6 weeks.

CTLA-4 inhibitor

Ipilimumab (Yervoy) and tremelimumab (Imjudo) are other types of drugs that boost the immune response, but they have a different target. They block CTLA-4, another protein on T cells that normally helps keep them in check.

Tremelimumab (Imjudo) can be used with another immunotherapy drug durvalumab as the first treatment for liver cancer that cannot be removed with surgery. It is given as an intravenous (IV) infusion once every 4 weeks.

Ipilimumab can be used in combination with nivolumab to treat liver cancer that has previously been treated (such as with the targeted drug sorafenib). This drug is given as an intravenous (IV) infusion, usually once every 3 weeks for 4 treatments.

Chemotherapy for liver cancer

Chemotherapy (chemo) is treatment with drugs to destroy cancer cells. Chemo may be an option for people whose liver cancer cannot be treated with surgery, has not responded to local therapies such as ablation or embolization, or when targeted therapy is no longer helpful.

Unfortunately, most chemo drugs do not have a great effect on liver cancer. Recent advances have shown that a combination of drugs may be more helpful than using just a single chemo drug. But even these combinations of drugs shrink only a small number of tumors, and the responses often do not last long. And most studies show systemic chemo has not helped patients live longer.

The most common chemotherapy drugs for treating liver cancer include:

  • Gemcitabine (Gemzar)
  • Oxaliplatin (Eloxatin)
  • Cisplatin
  • Doxorubicin (pegylated liposomal doxorubicin)
  • 5-fluorouracil (5-FU)
  • Capecitabine (Xeloda)
  • Mitoxantrone (Novantrone)

Sometimes, combinations of 2 or 3 of these drugs are used. GEMOX (gemcitabine plus oxaliplatin) is one option for people who are fairly healthy and may tolerate more than one drug. 5-FU based chemotherapy, for example with FOLFOX (5-FU, oxaliplatin and leucovorin), is another option for people with bad liver disease.

You can get chemotherapy in different ways.

Systemic chemotherapy

Drugs are injected right into a vein (IV) or taken by mouth. These drugs enter the bloodstream and reach almost all areas of the body, possibly making this treatment useful for cancers that have spread to other parts of the body.

For IV chemo, a slightly larger and sturdier catheter is required in the vein system to administer chemo. They are known as central venous catheters (CVCs), central venous access devices (CVADs), or central lines. They are used to put medicines, blood products, nutrients, or fluids right into your blood. They can also be used to take out blood for testing. Many different kinds of CVCs are available. The 2 most common types are the port and the PICC line.

Doctors give chemo in cycles, with each period of treatment followed by a rest period to give you time to recover from the effects of the drugs. Cycles are most often 2 or 3 weeks long. The schedule varies depending on the drugs used. For example, with some drugs, the chemo is given only on the first day of the cycle. With others, it is given for a few days in a row, or once a week. Then, at the end of the cycle, the chemo schedule repeats to start the next cycle.

Treatment for advanced liver cancer is based on how well it is working and what side effects you have.

Regional chemotherapy

Drugs are put right into an artery that leads to the part of the body with the tumor. This focuses the chemo on the cancer cells in that area. It reduces side effects by limiting the amount of drug reaching the rest of the body. Hepatic artery infusion, or chemo given directly into the hepatic artery, is regional chemotherapy that can be used for liver cancer.

Hepatic artery infusion (HAI)

Doctors have studied putting chemo drugs directly into the hepatic artery at a constant rate to see if it might be more effective than systemic chemo. This technique is known as hepatic artery infusion (HAI). It is slightly different from chemoembolization because surgery is needed to put an infusion pump under the skin of the abdomen (belly). The pump is attached to a catheter that connects to the hepatic artery. This is done while the patient is under general anesthesia. The chemo is injected with a needle through the skin into the pump’ reservoir and it is released slowly and steadily into the hepatic artery.

The healthy liver cells break down most of the drug before it can reach the rest of the body. This method gets a higher dose of chemo to the tumor than systemic chemo but doesn’t increase side effects. The drugs most commonly used for hepatic artery infusion (HAI) include floxuridine (FUDR), cisplatin, and oxaliplatin.

Hepatic artery infusion (HAI) may be used for people with very large liver cancers that cannot be removed with surgery or cannot be treated entirely with TACE. This technique may not be useful in all patients because it requires surgery to insert the pump and catheter, an operation that many liver cancer patients may not be able to tolerate.

Early studies have found that hepatic artery infusion (HAI) is often effective in shrinking tumors, but more research is still needed.

Possible side effects of chemotherapy for liver cancer

Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemo, which can lead to side effects.

The side effects of chemo depend on the type and dose of drugs given and the length of time they are taken. Common side effects include:

  • Hair loss
  • Mouth sores
  • Loss of appetite
  • Nausea and vomiting
  • Diarrhea
  • Increased chance of infections (from low white blood cell counts)
  • Easy bruising or bleeding (from low blood platelet counts)
  • Fatigue (from low red blood cell counts)

These side effects usually don’t last long and go away after treatment is finished. There are often ways to lessen them. For example, drugs can be given to help prevent or reduce nausea and vomiting. Be sure to ask your doctor or nurse about drugs to help reduce side effects.

Along with the possible side effects in the list above, some drugs may have their own specific side effects. Ask your health care team what you can expect.

You should report any side effects you notice while getting chemotherapy to your medical team so that you can be treated promptly. In some cases, the doses of the chemotherapy drugs may need to be reduced or treatment may need to be delayed or stopped to prevent side effects from getting worse.

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 1 and some stage 2 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. Important factors that may influence the outcome are 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. How well your liver is working 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. 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. A 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 under control.

Unresectable (inoperable) liver cancer that has not spread

Unresectable cancers include cancers that haven’t yet spread to lymph nodes or distant parts of the body, but that 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.
  • The person isn’t healthy enough for liver surgery.

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

These treatments are very unlikely to cure the cancer, but they can reduce symptoms and may even help a person live longer. Because these cancers can be hard to treat, clinical trials of newer treatments may offer a good option in many cases.

Advanced (metastatic) liver cancer (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 removed with surgery.

For people whose liver is functioning well enough (Child-Pugh class A or B), initial treatment options might include:

  • The immunotherapy drug atezolizumab (Tecentriq) plus the targeted drug bevacizumab (Avastin)
  • Either of the targeted drugs sorafenib (Nexavar) or lenvatinib (Lenvima)

If these drugs are no longer working, other targeted drugs, such as regorafenib (Stivarga), cabozantinib (Cabometyx), or ramucirumab (Cyramza) are possible options. Immunotherapy drugs such as pembrolizumab (Keytruda), or nivolumab (Opdivo) combined with ipilimumab (Yervoy), might also be helpful.

As with unresectable liver cancer that has not spread, clinical trials of newer targeted therapies, immunotherapy, new approaches to chemotherapy (new drugs and ways to deliver chemotherapy), new forms of radiation therapy, and other new treatments may be helpful. 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.

People with resectable cancer 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, immunotherapy, 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.

Supportive (palliative) care

Palliative care is specialized medical care that focuses on providing relief from pain and other symptoms of a serious illness. Palliative care specialists work with you, your family and your other doctors to provide an extra layer of support that complements your ongoing care. Palliative care can be used while undergoing other aggressive treatments, such as surgery, chemotherapy or radiation therapy.

When palliative care is used along with all of the other appropriate treatments, people with cancer may feel better and live longer.

Palliative care is provided by a team of doctors, nurses and other specially trained professionals. Palliative care teams aim to improve the quality of life for people with cancer and their families. This form of care is offered alongside curative or other treatments you may be receiving.

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 30, 31. At present, only 10% to 23% of patients with hepatocellular carcinoma may be surgical candidates for curative-intent treatment 32, 33. 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% 34.

Liver transplantation, surgical resection, and ablation offer high rates of complete responses and a potential for cure in patients with early hepatocellular carcinoma 16.

The natural course of advanced-stage hepatocellular carcinoma is better known. Untreated patients with advanced disease usually survive less than 6 months 35. 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 36.

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 37, 38.

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 2012 and 2018. The earlier liver and intrahepatic bile duct cancer is caught, the better chance a person has of surviving five years after being diagnosed. For liver and intrahepatic bile duct cancer, 43.9% are diagnosed at the local stage. The 5-year relative survival for localized liver and intrahepatic bile duct cancer is 36.1%.

The SEER database does not divide liver cancer survival rates by AJCC TNM stages. Instead, it groups cancer cases into summary stages 5:

  • 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 and intrahepatic bile duct cancer is about 36.1%.
  • 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 12.8%.
  • 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 3.1%.

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%.

Survival for liver cancer by age

5 year survival for liver cancer is generally higher in younger people compared to older people.

In men aged:

  • 15 to 39, almost 25 out of 100 (almost 25%) survive their liver cancer for 5 years or more
  • 80 to 99, around 5 out of 100 (around 5%) survive their liver cancer for 5 years or more

In women aged:

  • 15 to 39, 30 out of 100 (30%) survive their liver cancer for 5 years or more
  • 80 to 99, only 2 out of 100 (only 2%) survive their liver cancer for 5 years or more

Liver cancer survival by stage

The following statistics are published in the European Clinical Practice Guidelines for liver cancer (hepatocellular carcinoma). They are based on the Barcelona Clinic Liver Cancer (BCLC) staging system.

The Barcelona Clinic Liver Cancer (BCLC) staging system takes into account the size and location of the cancer, as well as how well your liver is working and your general health.

For each stage, there are statistics for:

  • median survival, which is the length of time from diagnosis to the point at which half of the patients are still alive
  • 5 year survival, which is the number of people who survive for 5 years or more after diagnosis

Stage 0

Without treatment, the median survival for stage 0 liver cancer is more than 3 years.

With treatment, between 70 and 90 out of 100 people (between 70 – 90%) will survive for 5 years or more.

To treat stage 0 liver cancer, you might have an operation to remove part of your liver (resection), a liver transplant, or treatment to destroy the cancer, usually with heat (ablation therapy).

Stage A

Without treatment, the median survival for stage A liver cancer is 3 years.

With treatment, between 50 and 70 out of 100 people (between 50 – 70%) will survive for 5 years or more.

To treat stage A liver cancer, you might have an operation to remove part of your liver, a liver transplant or treatment to destroy the cancer (ablation therapy).

Stage B

Without treatment, the median survival for stage B liver cancer is 16 months.

With treatment, the median survival for stage B liver cancer is 20 months.

To treat stage B liver cancer, you might have chemotherapy directly into the blood vessel feeding the tumour in the liver and blocking off the blood supply. This is called transarterial chemoembolisation or TACE.

Stage C

Without treatment, the median survival for stage C liver cancer is between 4 and 8 months

With treatment, the median survival for stage C liver cancer is between 6 and 11 months.

To treat stage C liver cancer, you might have a targeted cancer drug such as sorafenib. Or your doctor may suggest a clinical trial.

Stage D

Without treatment, the median survival for stage D liver cancer is less than 4 months.

There are no treatments that work well for stage D liver cancers. But your doctors and specialist nurses will continue to treat any symptoms you may develop.

References
  1. What Is Liver Cancer? American Cancer Society. https://www.cancer.org/cancer/liver-cancer/about/what-is-liver-cancer.html
  2. About Liver Cancer. https://www.dana-farber.org/liver-cancer
  3. Lotfollahzadeh S, Recio-Boiles A, Babiker HM. Liver Cancer. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448337
  4. Key Statistics About Liver Cancer. American Cancer Society. https://www.cancer.org/cancer/liver-cancer/about/what-is-key-statistics.html
  5. Liver and Intrahepatic Bile Duct Cancer — Cancer Stat Facts. https://seer.cancer.gov/statfacts/html/livibd.html
  6. Can Liver Cancer Be Found Early ? American Cancer Society. https://www.cancer.org/cancer/liver-cancer/detection-diagnosis-staging/detection.html
  7. Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. Lancet 362 (9399): 1907-17, 2003. https://www.ncbi.nlm.nih.gov/pubmed/14667750
  8. Arias-Flórez JS, Martínez-Delgado AM, Alarcón-Tarazona ML, Insuasty-Enriquez JS, Díaz-Martínez LA. Rendimiento diagnóstico de marcadores tumorales séricos convencionales en pacientes con sospecha clínica de cáncer primario metastásico a hígado [Conventional serum tumor markers in liver cancer. Retrospective analysis of 118 patients]. Rev Med Chil. 2018 Dec;146(12):1422-1428. Spanish. doi: 10.4067/s0034-98872018001201422
  9. Parizadeh SM, Jafarzadeh-Esfehani R, Ghandehari M, Goldani F, Parizadeh SMR, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Avan A. MicroRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma. Curr Drug Targets. 2019;20(11):1129-1140. doi: 10.2174/1389450120666190307095720
  10. Sayiner M, Golabi P, Younossi ZM. Disease Burden of Hepatocellular Carcinoma: A Global Perspective. Dig Dis Sci. 2019 Apr;64(4):910-917. doi: 10.1007/s10620-019-05537-2
  11. Puustinen L, Barner-Rasmussen N, Pukkala E, Färkkilä M. Incidence, prevalence, and causes of death of patients with autoimmune hepatitis: A nationwide register-based cohort study in Finland. Dig Liver Dis. 2019 Sep;51(9):1294-1299. doi: 10.1016/j.dld.2019.01.015
  12. Cowppli-Bony A, Colonna M, Ligier K, Jooste V, Defossez G, Monnereau A; le Réseau Francim; Réseau des registres de cancer Francim. Épidémiologie descriptive des cancers en France métropolitaine : incidence, survie et prévalence [Descriptive epidemiology of cancer in metropolitan France: Incidence, survival and prevalence]. Bull Cancer. 2019 Jul-Aug;106(7-8):617-634. French. doi: 10.1016/j.bulcan.2018.11.016
  13. Colombo M, Lleo A. Refining surgical therapy of liver cancer in cirrhosis: etiology makes the difference. Transl Gastroenterol Hepatol. 2018 Dec 14;3:104. doi: 10.21037/tgh.2018.12.03
  14. What Is Liver Cancer ? American Cancer Society. https://www.cancer.org/cancer/liver-cancer/about/what-is-liver-cancer.html
  15. Mavros MN, Mayo SC, Hyder O, et al.: A systematic review: treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma. J Am Coll Surg 215 (6): 820-30, 2012. https://www.ncbi.nlm.nih.gov/pubmed/22981432
  16. Bruix J, Sherman M; American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma: an update. Hepatology 53 (3): 1020-2, 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084991/
  17. Bosch FX, Ribes J, Borràs J: Epidemiology of primary liver cancer. Semin Liver Dis 19 (3): 271-85, 1999. https://www.ncbi.nlm.nih.gov/pubmed/10518307
  18. Beasley RP, Hwang LY, Lin CC, et al.: Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet 2 (8256): 1129-33, 1981. https://www.ncbi.nlm.nih.gov/pubmed/6118576
  19. Beasley RP: Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61 (10): 1942-56, 1988. https://www.ncbi.nlm.nih.gov/pubmed/2834034
  20. Sun CA, Wu DM, Lin CC, et al.: Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan. Am J Epidemiol 157 (8): 674-82, 2003. https://www.ncbi.nlm.nih.gov/pubmed/12697571
  21. Lok AS, Seeff LB, Morgan TR, et al.: Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 136 (1): 138-48, 2009. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749922/
  22. Bruix J, Sherman M. Management of hepatocellular carcinoma: An update. Hepatology (Baltimore, Md). 2011;53(3):1020-1022. doi:10.1002/hep.24199. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084991/
  23. Farinati F, Floreani A, De Maria N, et al.: Hepatocellular carcinoma in primary biliary cirrhosis. J Hepatol 21 (3): 315-6, 1994. https://www.ncbi.nlm.nih.gov/pubmed/7530737
  24. Forner A, Llovet JM, Bruix J: Hepatocellular carcinoma. Lancet 379 (9822): 1245-55, 2012. https://www.ncbi.nlm.nih.gov/pubmed/22353262
  25. Hessheimer AJ, Forner A, Varela M, et al.: Metabolic risk factors are a major comorbidity in patients with cirrhosis independent of the presence of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 22 (10): 1239-44, 2010. https://www.ncbi.nlm.nih.gov/pubmed/20505515
  26. Jaskiewicz K, Banach L, Lancaster E: Hepatic siderosis, fibrosis and cirrhosis: the association with hepatocellular carcinoma in high-risk population. Anticancer Res 17 (5B): 3897-9, 1997 Sep-Oct. https://www.ncbi.nlm.nih.gov/pubmed/9427800
  27. Sun Z, Lu P, Gail MH, et al.: Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1. Hepatology 30 (2): 379-83, 1999. https://www.ncbi.nlm.nih.gov/pubmed/10421643
  28. Signs and Symptoms of Liver Cancer. American Cancer Society. https://www.cancer.org/cancer/liver-cancer/detection-diagnosis-staging/signs-symptoms.html
  29. Liver Cancer Stages. American Cancer Society. https://www.cancer.org/cancer/liver-cancer/detection-diagnosis-staging/staging.html
  30. Barbara L, Benzi G, Gaiani S, et al.: Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatology 16 (1): 132-7, 1992. https://www.ncbi.nlm.nih.gov/pubmed/1352268
  31. Ebara M, Ohto M, Shinagawa T, et al.: Natural history of minute hepatocellular carcinoma smaller than three centimeters complicating cirrhosis. A study in 22 patients. Gastroenterology 90 (2): 289-98, 1986. https://www.ncbi.nlm.nih.gov/pubmed/2416627
  32. Shah SA, Smith JK, Li Y, et al.: Underutilization of therapy for hepatocellular carcinoma in the medicare population. Cancer 117 (5): 1019-26, 2011. https://www.ncbi.nlm.nih.gov/pubmed/20945363
  33. Sonnenday CJ, Dimick JB, Schulick RD, et al.: Racial and geographic disparities in the utilization of surgical therapy for hepatocellular carcinoma. J Gastrointest Surg 11 (12): 1636-46; discussion 1646, 2007. https://www.ncbi.nlm.nih.gov/pubmed/17912593
  34. Dhir M, Lyden ER, Smith LM, et al.: Comparison of outcomes of transplantation and resection in patients with early hepatocellular carcinoma: a meta-analysis. HPB (Oxford) 14 (9): 635-45, 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461390/
  35. Okuda K, Ohtsuki T, Obata H, et al.: Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56 (4): 918-28, 1985. https://www.ncbi.nlm.nih.gov/pubmed/2990661
  36. Llovet JM, Bruix J: Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 37 (2): 429-42, 2003. https://www.ncbi.nlm.nih.gov/pubmed/12540794
  37. Llovet JM, Brú C, Bruix J: Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19 (3): 329-38, 1999. https://www.ncbi.nlm.nih.gov/pubmed/10518312
  38. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 28 (3): 751-5, 1998. https://www.ncbi.nlm.nih.gov/pubmed/9731568
Health Jade Team

The author Health Jade Team

Health Jade