Causes and Risk Factors for Hepatocellular Carcinoma

Overview

Hepatocellular carcinoma (HCC) is a type of liver cancer. Liver cancer is caused by a change (mutation) in the DNA of liver cells. The DNA mutation results in an abnormality in the way liver cells are produced. Liver cells may grow out of control and form a mass (tumor) of cancerous cells.

There are a number of factors that are related to developing HCC. These are called risk factors. A risk factor increases the chances of developing a condition compared to a person who does not have the risk factor. Some risk factors are non-modifiable, which means a person cannot change or control the factor. Other risk factors are modifiable, which means a person potentially can change or control the factor through health behavior and lower their risk.

HCC is associated with several risk factors. While these are some known risk factors for HCC, it's important to remember that not everyone who has these risk factors will develop liver cancer. Additionally, there may be other factors involved in the development of HCC that are still being studied by researchers.

Non-modifiable Risk Factors (Risk Factors You Can't Change)

Non-modifiable risk factors for HCC are factors that cannot be changed or controlled. These include:

• Age: HCC is uncommon in people younger than 40 years old. HCC is most often diagnosed in people around age 70 years old
• Sex Assigned at Birth: People assigned male at birth have a higher risk of developing HCC compared to those assigned female at birth.
• Genetics: Certain inherited conditions can increase the risk of developing HCC. Examples include hereditary hemochromatosis and Wilson's disease. These genetic conditions affect how the body processes iron and copper, respectively, and can lead to an increased risk of liver cancer.
• Race or Ethnicity: In the U.S., people who are Black, Hispanic, and Asian have higher rates of HCC than people who are white.

It is essential to remember that having non-modifiable risk factors does not mean that an individual will definitely develop HCC. These factors simply indicate an increased risk compared to individuals without these risk factors. It's always a good idea to discuss any concerns or questions about your personal risk factors with your healthcare provider.

Modifiable Risk Factors (Factors You May Be Able to Change)

It is important to identify and understand the modifiable risk factors for HCC, as they are factors that can be changed or controlled to reduce the risk of developing this type of cancer. Here are some modifiable risk factors for HCC:

• Chronic viral hepatitis: Chronic infection with the hepatitis B or hepatitis C virus accounts for about 80% of HCC diagnoses globally. In the United States and Europe, hepatitis C is more common as a cause of HCC, while in other parts of the world, hepatitis B is more prevalent. Both hepatitis B and hepatitis C are transmitted through blood exposure. Exposure to hepatitis B and hepatitis C may occur through:
  • Sexual contact: Anal intercourse is a particular risk factor for hepatitis B or hepatitis C transmission
  • Sharing needles: Sharing needles, syringes or other equipment to prepare and inject drugs increases the risk of hepatitis B or hepatitis C exposure
  • Procedures: Contaminated equipment or improperly sterilized equipment used in medical procedures or tattooing are risks for hepatitis B or hepatitis C exposure.
• Excessive alcohol consumption: Drinking too much alcohol can damage the liver and is linked to 30% of HCC diagnoses in the United States. Research suggests that having three or more drinks per day increases the risk of HCC by 16%. Alcohol can cause liver damage and inflammation, which can eventually lead to liver cancer. Limiting alcohol consumption or avoiding it altogether can lower the risk.
• Nonalcoholic fatty liver disease (NAFLD): NAFLD occurs when there is an accumulation of fat in the liver. It is commonly associated with conditions like obesity and diabetes. About 10% to 20% of HCCs in the United States are related to NAFLD. NAFLD may also be called metabolic dysfunction-associated steatotic liver disease (MASLD).
• Obesity: Being overweight or obese is associated with an increased risk of HCC. Obesity is defined as having a body mass index (BMI) of 30 or higher. Maintaining a healthy weight through regular physical activity and a balanced diet can help reduce the risk.
• Unhealthy Diet: Certain dietary habits can increase the risk of HCC. Consuming excessive amounts of red meat, saturated fat, cholesterol, and sugar has been linked to an increased risk. On the other hand, a diet rich in n-3 polyunsaturated fatty acids (found in fish and poultry), vegetables, and fiber has been associated with a lower risk of HCC.
• Smoking: Smoking tobacco products is a well-known risk factor for various types of cancer, including HCC. Smoking can lead to liver fibrosis and liver cancer. Quitting smoking or avoiding tobacco products altogether can help reduce the risk.

It's important to note that having these modifiable risk factors doesn't mean that someone will definitely develop HCC. However, individuals with these risk factors have an increased likelihood compared to those without them. If you have one or more of these risk factors, it may be beneficial to discuss with your doctor about starting surveillance for HCC, which involves regular monitoring for early detection.

Reducing Risks

There are several actions that a person can take to modify their risk factors and potentially prevent or reduce the chances of getting HCC. Here are some important steps to consider:

• Protect against viral infections: Certain viral infections, such as hepatitis B virus (HBV) and hepatitis C virus (HCV), are major risk factors for HCC. Taking preventive measures like:
  • Consider receiving vaccines to protect against hepatitis B virus. Consult with your healthcare professional about vaccines that may help protect against infection.
  • Reduce exposure to hepatitis B or hepatitis C, including reducing high-risk sexual activity and sharing of needles.
• Moderate alcohol consumption: Limit alcohol consumption to 1 drink or less per day for women or 2 drinks or less per day for men. People with liver disease should try to not drink alcohol at all.
• Stop smoking: Stop smoking and avoid secondhand tobacco smoke.
• Healthy eating: Eating a healthy diet that includes fruits, vegetables, whole grains, fish, and poultry can also help lower the risk of developing HCC.
• Follow recommended screening guidelines: Regular screening tests can help detect early signs of HCC or pre-cancerous conditions that may lead to HCC.

It's important to note that while these actions may help reduce the risk of developing HCC, they are not guaranteed preventive measures. It's always advisable to consult with a healthcare provider who can provide personalized guidance based on individual health history and risk factors.