Liver Cancer

What Is Liver Cancer?

Liver cancer is a type of cancer that starts in the liver. Cancer starts when cells in the body begin to grow out of control.

The liver

The liver is the largest internal organ. It lies under your right ribs just beneath your right lung. It has two lobes (sections).

The liver is made up mainly of cells called hepatocytes. It also has 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 carry bile from the liver to the gallbladder or directly to the intestines.

You cannot live without your liver. It has many important functions:

1. • It 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.
2. • It makes most of the clotting factors that keep you from bleeding too much when you are cut or injured.
3. • It delivers bile into the intestines to help absorb nutrients (especially fats).
4. • It breaks down alcohol, drugs, and toxic wastes in the blood, which then pass from the body through urine and stool

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

Types of liver cancer

Primary liver cancer

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

Hepatocellular carcinoma (HCC)

This is the most common form of liver cancer in adults.

Hepatocellular cancers can have different growth patterns:

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

Doctors can classify several subtypes of HCC. Most often these subtypes do not affect treatment or prognosis (outlook). But one of these subtypes, fibrolamellar, is important to recognize. It is rare, making up less than 1% of HCCs and is most often seen in women younger than age 35. Often the rest of the liver is not diseased. This subtype tends to have a better outlook than other forms of HCC.

Most of the rest of this content refers only to hepatocellular carcinoma and is called liver cancer.

Intrahepatic cholangiocarcinoma (bile duct cancer)

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

Although the rest of this information is mainly about hepatocellular cancers, cholangiocarcinoma are often treated the same way.

Angiosarcoma and hemangiosarcoma

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

These tumours grow quickly and are usually too widespread to be removed surgically by the time they are found. But these cancers are usually very hard to treat. These cancers are treated like other sarcomas.

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 called a secondary liver cancer. These tumours 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. It is also treated as lung cancer.

Hepatic adenoma

Hepatic adenoma is a benign tumour 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 tumour could rupture (leading to severe blood loss) and a small risk that it could eventually develop into liver cancer.

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

Risk Factors

A risk factor is anything that increases a person’s 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, cannot be changed. But having a risk factor, or even several, does not mean that you will get the disease. And some people who get the disease may have few or no known risk factors.

Several risk factors can make you more likely to develop lung cancer. These factors are related to the risk of lung cancer in general. It’s possible that some of these might not apply to small cell lung cancer (SCLC).

Risk factors you can change

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

But 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.

Factors that can increase your risk of liver cancer

Several factors can increase a person's chance of getting a hepatocellular carcinoma (HCC).

Sex

Hepatocellular carcinoma is much more common in men than in women. Much of this is probably because of behaviours affecting some of the risk factors described below. The fibrolamellar subtype of HCC is more common in women.

Chronic viral hepatitis

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 India infection with hepatitis C is the more common cause of HCC, while in Asia and developing countries, hepatitis B is more common. 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).

HBV and 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 India 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.

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 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.

HCV, on the other hand, is less likely to cause symptoms. But most people with 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.

Cirrhosis

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

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease is a common condition in obese people. People with a subtype of this disease, known as non-alcoholic steatohepatitis (NASH), might go on to develop cirrhosis.

Primary biliary cirrhosis

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

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 India , which in turn is linked with an increased risk of liver cancer.

Tobacco use

Smoking increases the risk of liver cancer. People who smoked and stopped have a lower risk than those who still smoke, but both groups have a higher risk than those who never smoked.

Obesity

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

Type 2 diabetes

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

Aflatoxins

These cancer-causing substances are made by a fungus that contaminates peanuts, wheat, soybeans, ground nuts, corn, and rice. Storage in a moist, warm environment can lead to the growth of this fungus. Although this can occur almost anywhere in the world.

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

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.

What Causes Liver Cancer?

Although several risk factors for liver cancer are known , exactly how these may lead normal liver cells to become cancerous is only partially understood. Some of these risk factors affect the DNA of cells in the liver, which can result in abnormal cell growth and may cause cancers to form.

DNA is the chemical in our cells that carries our genes which control how our cells function. We look like our parents because they are the source of our DNA. But DNA affects more than just how we look.

Some genes control when cells grow, divide into new cells, and die.

1. • Genes that help cells to grow and divide and stay alive are called oncogenes.
2. • Genes that keep cell division under control, repair mistakes in DNA, or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes (mutations) 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.

Hepatitis viruses can also change DNA when they infect liver cells. In some patients, the virus's DNA can insert itself into a liver cell's DNA, where it may turn on the cell's oncogenes.

Liver cancer clearly has many different causes, and there are undoubtedly many different genes involved in its development.