There are several risk factors for liver cancer. Interestingly, these risk factors vary based on prevelance. In areas where liver cancer is most common, the risk factors are primarily infections from food contaminated with mycotoxin aflatoxin B1 and hepatitis B. In areas where liver cancer is less common, the major risk factors are hepatitis C virus infection, excessive alcohol consumption, obesity and diabetes.
Hepatitis B Virus
Chronic infection with HBV infection is the number one cause of HCC in Asia and Africa. Hepatitis B infection results from infection with the Hepatitis B Virus, which is transmitted by blood and body fluids. Chronic infection with HBV can result in cirrhosis and even liver cancer. Of the two billion people that have been infected with HBV, about 18% are chronically infected. Development of liver cancer can occur within 5 to 75 years after infection. HBV is transmitted through bodily fluids such as blood, semen and vaginal fluids. HBV was labeled as a human carcinogen in 1994 by the International agency for Research on Cancer (IARC). The risk of a hepatitis B infection becoming chronic is highly influenced by the age of infection. People infected during infancy or their childhood are more likely to develop chronic hepatitis B. Chronic infection with HBV increases the likelihood of developing liver cancer greatly also.
Hepatitis C Virus
While HBV is the leading cause of liver cancer in high incidence regions, HCV is the leading cause in low incidence regions like Europe and the North America and Japan. Hepatitis C virus (HCV) is a blood-borne virus that was labeled a carcinogen by the IARC in 1994. Of the 180 million people infected with the virus, 72% are chronic carriers. The virus is primarily transmitted through products contaminated with blood, but can also be acquired from other bodily fluids. Nearly 1 in 5 people with chronic HCV will develop HCC by the age of 75.
Aflatoxins are carcinogenic chemicals produced by the fungal species Aspergillus flavus and A. parasiticus. These molds grow on food stables such as cereals, corn and other vegetation and grains. These foods are often contaminated during crop cultivation. Spreading of these toxins can be enhanced by poor food storage conditions that promote fungal growth and toxin production. Nearly 4.5 billion people have been exposed to these toxins, with the highest exposure rates in East and Southeast Asia and Sub-Saharan Africa. While these toxins increase risk for liver cancer, the risk is especially high in people with chronic HBV.
Aflatoxins are thought to promote liver cancer by binding to and mutating the DNA, since nearly half of HCC tumors have this mutation in tumor suppressor gene TP53 in areas where aflatoxin exposure is high, but not in areas of low exposure.
Multiple organizations including IARC and the National Institute of Alcohol Abuse and Alcoholism (NIAAA) have found that persistent heavy drinking is associated with primary liver cancer and identified it as a carcinogen for the liver. Heavy drinking primarily causes liver cancer through cirrhosis. In populations where HBV is low, alcohol-related cirrhosis is the primary risk factor for liver cancer. These include high income countries such as the United States and northern European countries. Alcohol synergistically enhances the effects of tobacco consumption and chronic hepatitis on liver cancer. Specifically in the case of tobacco, alcohol increases the exposure of hepatocytes to carcinogens from tobacco smoke.
When alcohol is consumed it is converted into acetaldehyde which is further oxidized to create acetate (IARC, 2012). Aldehyde may promote cancer by binding to DNA to cause mutations that can result in uncontrolled cell proliferation. Alternatively, the alcohol can cause injury to liver cells which can result in fibrogenesis or the formation of excess connective tissue which can lead to cirrhosis.
Flatworms (Liver Flukes)
For the less common liver cancer, cholangiocarcinoma, flatworms or liver flukes are the primary risk factor. Specifically Opisthorchis viverrini and Clonorchis sinensis were the primary causes of liver cancer. These worms are most common in Eastern Asia. Approximately, 17% of people with these worms develop cholangiocarcinoma. The worms live in the bile duct and can survive for more than two decades for C. sinensis and less than 10 years for O. viverrini (Sithithaworn & Haswell-Elkins, 2003). These worms are primarily transmitted through snails and the cyprinid fish, especially in cultures where eating raw fish is popular. Contamination of snail and fish water habitats with feces infested with eggs in regions with poor sanitation also contributes to it spreading.
Metabolic Syndrome and Obesity
Cirrohosis can also be caused by obesity. Obesity-related non-alcoholic fatty liver disease (NAFD) is increasing in high income countries and it is believed that this risk factor may grow among low- and middle-income countries as well. There is also evidence that risk factors associated with metabolic syndrome including insulin resistance, hypertension, dyslipidemia, and obesity, could cause non-alcoholic hepatosteatosis, cirrhosis and HCC. However more research is needed on this topic.