Causes and Risk Factors of Liver Cancer

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We don't know the precise causes of liver cancer, but risk factors include excessive alcohol use, smoking, liver infections such as hepatitis B and hepatitis C, certain other medical and genetic conditions, and other concerns. Since there is no screening test for liver cancer at this time, being aware of your risk factors and knowing the signs and symptoms is the best approach for finding liver cancer in the earlier, more treatable stages.

Liver cancer can affect both children and adults but occurs most often in adults. There are several types of liver cancer, but the risk factors below refer to adult primary liver cancer, called hepatocellular carcinoma and bile duct cancer (cholangiocarcinoma). Studies have found that liver cancer and bile duct cancer are increasing worldwide, and are the leading cause of cancer deaths in some regions.

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© Verywell, 2018 

Common Risk Factors

Cancer begins when a series of gene mutations lead a cell to grow out of control. How this happens in liver cancer isn't confirmed, but several mechanisms have been postulated. What is known is that several factors increase one's risk of developing the disease. Some of them do so substantially, whereas others may raise the risk only a small amount. There are other risk factors that are considered, though experts aren't sure if they are indeed related.

It's important to note that having a risk factor for liver cancer does not mean that you will develop the disease. It is usually a combination of factors working together that results in the development of a tumor. Combinations of risk factors can be additive, but can also be multiplicative, such as with the combinations of alcohol and smoking or hepatitis B and smoking. But, people may also develop liver cancer when they don't have any of the currently known risk factors for the disease.

Known risk factors include:

Race and Sex

Asians and Pacific Islanders develop liver cancer more often than people of other races, largely due to the hepatitis epidemic among these regions. Caucasians develop liver cancer less frequently, but the disease appears to be increasing. Liver cancer is also much more common in men than women, although the reasons aren't entirely clear.

Hepatitis B Infection

Chronic hepatitis B infection is a major risk factor for the development of liver cancer and is the leading cause of liver cancer in Africa and most of Asia. Around 95 percent of people clear the virus once they are infected, but roughly 5 percent become chronic carriers of the disease. It is these people who are at risk for the development of liver cancer, though some people with chronic hepatitis B are at more risk than others.

Treatments are available, but many people are not aware they carry the virus or live in an area in which medical care is less than optimal. Overall, hepatitis B carriers are 100 times more likely to develop liver cancer, and 2.5 percent of people with cirrhosis due to hepatitis B (and 0.5 to 1 percent of people without cirrhosis) will develop the disease each year.

Hepatitis C Infection

Hepatitis C is also a major risk factor for the development of liver cancer and is currently the leading cause of liver cancer in the United States, Europe, and Japan. Unlike hepatitis B, many people do not clear the virus, and it becomes a progressive disease. Roughly 10 to 30 percent of people who are infected go on to develop cirrhosis.

Sadly, most people are unaware they are infected, and it's recommended that all American adults who were born between 1945 and 1965 be tested. When hepatitis C is found and treated with antiviral medications, the risk of cirrhosis, and likely liver cancer can be greatly reduced.

Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease is a condition similar to alcoholic liver disease, but it results in an accumulation of fat in the liver (fatty liver) by a different mechanism. It's thought to be an autoimmune disease (in which the body makes antibodies against itself) and may have a genetic component. With NAFLD, the risk of liver cancer is around four times higher than the general population. Closely related, metabolic syndrome may also be a risk factor for liver cancer.

Immunosuppression 

Immunosuppression increases the risk of liver cancer, as well as other cancers. Having HIV/AIDS is associated with a five-fold greater risk of developing liver cancer. Organ transplant recipients are twice as likely to develop liver cancer as the general population, and the risk is even higher for those who have received a liver transplant.

Lupus (Systemic Lupus Erythematosus)

The reason is uncertain, but people who have lupus are more than twice as likely to develop liver cancer.

Diabetes

People who have diabetes have a risk of liver cancer two to three times higher than the general population. Of interest, it appears that the diabetic medication Glucophage (metformin) may reduce this risk.

Chemical Exposures (and Occupational Risk)

A number of chemical exposures have been linked to the development of liver cancer and are probable carcinogens.

One exposure that the general public may encounter is arsenic in well water. Occupational exposures are also of concern, including exposure to vinyl chloride (found in plastics), acrylamide, PFOA or perfluorooctanoic acid (found in dry cleaning methods), polychlorinated biphenyls (PCBs), perfluorinated chemicals (PFCs), benzo(a)pyrene (BaP), and trichloroethylene.

Sclerosing Cholangitis

Sclerosing cholangitis is a chronic liver disease associated with inflammatory bowel disease (such as Crohn's disease that involves the colon and ulcerative colitis). Sclerosing cholangitis causes inflammation and scarring of the bile ducts such that bile backs up into the liver causing scarring there as well. It's thought that 10 percent to 15 percent of people with the disease will develop cholangiocarcinoma (bile duct cancer).

Aflatoxin Exposure

Though an uncommon risk factor in the United States, this is a more significant one worldwide. Aflatoxin B1 is a toxin produced by fungi (of the genus Aspergillus) that grows on foods such as wheat, peanuts, other groundnuts, soybeans, and corn. The toxin causes damage to the p53 gene in liver cells—a tumor suppressor gene that helps repair damaged DNA and inhibit the growth of harmful cells. Research is ongoing and studies are exploring whether aflatoxin causes liver cancer on its own or as a co-factor when combined with hepatitis B.

Strict food regulations and testing make this exposure uncommon in the United States, through exposure and poisoning is common worldwide. The toxin is often found in foods that have not been stored properly, usually in warm and tropical climates. American travelers to such areas likely should not worry, though—it's thought that long-term exposure is required to cause liver cancer.

Genetics

Liver cancer can run in families (even without a known genetic disease), and having a relative with the disease (on either side) increases your risk. The risk is greatest when it is a first degree relative such as a parent, sibling, or child.

Some known genetic diseases also affect risk, including:

Hemochromatosis

Hereditary hemochromatosis (iron overload disease) is a condition marked by the body's increased absorption and storage of iron, often in the liver. In time, the condition usually leads to cirrhosis and liver failure (as well as other medical problems).

The risk of liver cancer in people who have hemochromatosis is 20 times higher than that of the general population. Treatment (periodically withdrawing blood) can reduce the risk of problems, but many people are unaware they have the condition until they develop problems. It's thought that 1 million people in the United States are affected by one of the types of hemochromatosis.

Primary Biliary Cirrhosis

Primary biliary cirrhosis is a condition that appears to have a genetic component, as it runs in families. It is a progressive, autoimmune disease in which bile builds up in the liver, damaging bile ducts and leading to liver damage and cirrhosis. Primary biliary cirrhosis is associated with a high risk of liver cancer, similar to that found in people with chronic hepatitis C. 

Wilson's Disease

Wilson's disease is a rare genetic disorder characterized by the accumulation of copper in the body and is thought to be a risk factor for liver cancer.

Other Hereditary Diseases

Other hereditary diseases that may increase the risk of liver cancer include alpha-1 antitrypsin deficiency, tyrosinemia, acute hepatic porphyrias, porphyria cutanea tarda, and glycogen storage disease.

Lifestyle Risk Factors

Lifestyle factors are important in the development of liver cancer. While you cannot control many of the common risk factors mentioned above, you do have the ability to influence these.

Excessive, Long-Term Alcohol Use

Excessive, long-term use of alcohol can cause a number of liver diseases, including alcoholic hepatitis and alcoholic liver disease. Over time, cirrhosis develops with marked scarring of the liver, and often, liver failure. Liver cancer is primarily associated with heavy drinking, or the intake of more than three drinks on a daily basis, though lesser amounts can still cause significant and irreversible liver disease.

Alcohol intoxication, though not associated with liver cancer over the short term, may increase the risk of behaviors associated with acquiring hepatitis B or C.

Smoking

Smoking is a risk factor for many cancers, and liver cancer is no exception. Several studies suggest a link between smoking and liver cancer, and those who both smoke and drink heavily have a significantly greater risk of the disease.

Children who are born to parents who smoked either before or during pregnancy are at an increased risk of a rare type of liver cancer called hepatoblastoma.

Obesity

The role of obesity in liver cancer is uncertain by itself, but obesity does increase the risk of developing non-alcoholic liver disease, a condition that quadruples the risk of liver cancer, as well as diabetes, which is associated with triple the risk.

Anabolic Steroid Use

Anabolic steroids, such as those used by weightlifters, are a risk factor for liver disease and liver cancer.

Chewing Betel Quid

Uncommon in the United States, chewing betel quid is a risk factor for liver cancer in regions where this is commonly practiced.

Other Risk Factors

There is some evidence that gallbladder removal (cholecystectomy) increases risk, though researchers are not certain of the connection. The jury's also out on whether there is an increased risk related to current use of birth control pills.

It's thought there is some risk related to medical radiation (such as CT scans of the abdomen), but this risk is likely largely outweighed by the potential benefits of such treatment.

The parasite that causes schistosomiasis has been studied for its possible role in liver cancer. Instead of being a risk factor, it's thought that it is a co-factor in liver cancer related to hepatitis B and C infections.

Autoimmune hepatitis and gallstones are also risk factors for liver cancer.

How a Liver Cancer Diagnosis Is Made
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