A risk factor is anything that affects your chance of getting a disease, such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person's age or family history, can't be changed.
But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that you will get the disease. And some people who get the disease may have few or no known risk factors.
Scientists have found several risk factors that make a person more likely to develop hepatocellular carcinoma (HCC).
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 HCC is more common in women.
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 (Hep-B or Hep-C)
Worldwide, the most common risk factor for liver cancer is chronic (long-term) infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). These infections lead to cirrhosis of the liver (see above) and are responsible for making liver cancer the most common cancer in many parts of the world.
In the United States, 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 standard 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 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.
HBV 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 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 is a disease in which liver cells become damaged and are replaced by scar tissue. People with cirrhosis have an increased risk of liver cancer. Most (but not all) people who develop liver cancer already have some evidence of cirrhosis.
There are several possible causes of cirrhosis. Most cases in the United States occur in people who abuse alcohol or have chronic HBV or HCV infections.
Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease, a condition in which people who consume little or no alcohol develop a fatty liver, is common in obese people. People with a type of this disease known as non-alcoholic steatohepatitis (NASH) might go on to develop cirrhosis.
Primary biliary cirrhosis
Some types of autoimmune diseases that affect the liver can also cause cirrhosis. For example, there is also a disease called primary biliary cirrhosis (PBC). In 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 United States, which in turn is linked with an increased risk of liver cancer.
Being obese (very overweight) increases the risk of developing liver cancer. This is probably because it can result in fatty liver disease and cirrhosis.
Type 2 diabetes
Type 2 diabetes has been linked with an increased risk of liver cancer, usually in patients who also have other risk factors such as heavy alcohol use and/or chronic viral hepatitis. This risk may be increased because people with type 2 diabetes tend to be overweight or obese, which in turn can cause liver problems.
Certain rare diseases
Diseases that increase the risk of liver cancer include:
- Alpha1-antitrypsin deficiency
- Porphyria cutanea tarda
- Glycogen storage diseases
- Wilson disease
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, 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 in foods through testing.
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 (see What is liver cancer?). 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 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.
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.
Smoking increases the risk of liver cancer. Former smokers have a lower risk than current smokers, but both groups have a higher risk than those who never smoked.
Factors with unclear effects on liver cancer risk
Birth control pills
In rare cases, birth control pills, also known as oral contraceptives, can cause benign tumors called hepatic adenomas. But it is not known if they increase the risk of hepatocellular cancer. Some of the studies that have looked at this issue have suggested there may be a link, but most of the studies were not of high quality and looked at types of pills that are no longer used. Current birth control pills use different types of estrogens, different estrogen doses, and different combinations of estrogens with other hormones. It is not known if the newer pills increase liver cancer risk.