In Western countries  hepatocellular carcinoma (HCC) in adults nearly always develops from cirrhosis, a disease in which liver tissue is replaced by scar tissue.  It can be caused by long-term liver damage and liver inflammation (hepatitis) and involves the destruction of liver cells.

In Western countries  less than 20% HCC develop without underlying cirrhosis. The main causes of cirrhosis and liver cancer are chronic alcohol abuse and chronic viral infections (caused by  hepatitis C or B virus).  Other risk factors that can lead to liver damage and may thus cause liver cancer include:  inherited disorders of iron metabolism, substances produced by molds in food (aflatoxin), obesity and/or diabetes mellitus, some anabolic agents and certain chemical substances (thorotrast).  Occupational and genetic factors and even nicotine play a role in the development of liver cancer.

Risk factor: virus infections

Chronic infections with either hepatitis B or C viruses are the most important causes of cirrhosis and liver cancer in most parts of the world. Hepatitis B viruses, which can be transmitted through contact with body fluids (blood, semen, vaginal fluid, etc.), lead to inflammation of the liver (hepatitis).  Chronic hepatitis B infections are particularly common in Asia and Africa, while chronic hepatitis C infection is the leading problem in the U.S.A., Japan and Europe.

In adults hepatitis B infection runs a chronic course in less than 10 percent of persons  infected. Howeber, chronic disease is observed in more than 50 percent of those with hepatitis C infections.  Adults in whom chronic hepatitis C has already led to cirrhosis must be expected to develop hepatocellular carcinoma at an annual rate of 1 to 4 percent.  It usually takes 20 to 30 years for liver cancer to develop in people with chronic hepatitis C.

The rising incidence of liver cancer in the Western world over the last 30 years is primarily due to the increase in hepatitis C infections from the 1960s to the 1980s.  Hepatitis C has only been detectable since the 1990s.  In previous decades the virus could thus be inadvertently transmitted through stored blood and blood preparations as well as during other medical interventions or serial vaccinations.

Risk factor: alcohol consumption

Alcohol is considered to be the most important risk factor for liver cancer after hepatitis C and B virus infections.  Drinking alcohol for many years can lead to chronic inflammation (hepatitis) and destruction of liver tissue, which can progress to cirrhosis and liver cancer.

The World Health Organization (WHO) defines moderate alcohol consumption as up to 10 g per day for women and up to 20 g per day for men.  The WHO also recommends at least 1 to 3 alcohol-free days per week.  Consumption of 40-60 grams of pure alcohol per day is sufficient to cause liver damage in men.  Women react much more sensitively; 20-30 grams of alcohol per day (for example, a quarter liter of wine) puts their liver at risk.

The liver is particularly sensitive to alcohol if a chronic hepatitis B or C virus infection has already developed.  The combination of several risk factors multiplies the risk of cancer.  Thus, people with chronic hepatitis C or B virus infection should not drink alcoholic beverages at all.  People are also advised against alcohol consumption if they have liver damage caused by the so-called iron storage disease (hemochromatosis) or by some other metabolic disease affecting liver function.

Risk factor: nutrition

Another important risk factor is aflatoxin, a poisonous substance produced by molds, which may be present in contaminated food (in cereal products, for example).  However, this risk factor is found mainly in tropical and subtropical countries with a warm and humid climate.   

Beyond that, there are no special food components or diets that promote or prevent hepatocellular carcinoma (HCC).
Obesity and diabetes mellitus can increase the risk of HCC.

Drinking coffee, on the other hand, lowers the risk of chronic liver diseases and liver cancer. According to epidemiological studies the more coffee one drinks, the lower the risk of liver cancer. People with liver disease are therefore advised to drink coffee.

Risk factor: drugs

Sex hormones (oral contraceptives, anabolic agents) can also lead to liver damage and can thus promote the growth of liver tumors.  However, the new low-dose oral contraceptives increase the risk only slightly in the absence of liver disease.  People with chronic hepatitis B or C virus infections are advised against taking oral contraceptives.

Male sex hormones can also promote the development of a liver tumor.  A markedly increased risk is associated particularly with the unmonitored intake of male sex hormones to build muscles (anabolic agents).

Most drugs have no direct influence on the development of carcinomas.  Since drugs are often metabolized and eliminated via the liver, however, they should be taken in low doses or completely avoided by people with cirrhosis and/or liver cancer.

Risk factor: occupational factors

Certain occupational groups are at increased risk of developing health problems.  This applies particularly to occupations associated with a higher risk of hepatitis B and C virus infection.  High-risk individuals include medical healthcare workers who come in contact with blood and other body fluids from patients – for example, doctors, dentists, assistants, nurses, and cleaning staff.  A vaccination provides protection against hepatitis B virus infection.

An increased risk of cancer is also linked to frequent contact with certain chemical substances – for example, certain solvents, pesticides or insecticides.  These substances enter the body through the nose, mouth or skin and can cause liver damage that may ultimately result in liver cancer.   However, such substances play a very subordinate role as risk factors compared to hepatitis C and B virus infections and alcohol.

Risk factor: genetic factors

Various inherited metabolic diseases are associated with an increased risk of liver cancer.  The most common among them is the so-called iron storage disease (hemochromatosis), in which increased iron absorption from food leads to iron overload. In the course of decades, iron deposits throughout the body cause damage to many organs, including the liver (cirrhosis). An estimated 30 percent of patients with hemochromatosis and cirrhosis develop hepatocellular carcinoma. If hemochromatosis is detected early, the amount of iron in the body can be reduced by regular blood-letting. This can prevent long-term damages like cirrhosis and liver cancer.

Liver cancer seldom develops in conjunction with primary biliary cirrhosis (a chronic disease that first affects the bile capillaries in the liver), autoimmune hepatitis, Wilson’s disease (disorder of copper metabolism) or inherited alpha-1 antitrypsin deficiency .

Conclusion

The list of risk factors shows that you yourself can help reduce your risk of liver disease:

• First of all, you should abstain from excessive alcohol consumption for the sake of your health !
•  Hepatitis B and C virus (HBV and HCV) infections can often be prevented by taking appropriate precautions.  To do so, it is important to know how these viruses are transmitted.  The best protection against hepatitis B infection is provided by vaccination and regular immune monitoring; the HBV vaccination was the first effective anticancer vaccination.  People who are not effectively protected by vaccination are at particularly high risk of becoming infected by unprotected sexual contact with people suffering from hepatitis B.  The virus (HBV) is present in all body fluids - for example, blood, semen, vaginal fluid, and saliva. Generally speaking, people who frequently change sexual partners are at higher risk of infection.  Both hepatitis B and C are also transmitted by blood-to-blood contact.  A particularly high risk is associated with occupational exposure to blood from patients.  Intravenous drug users are also at high risk of infection if they share needles.  Tattooing and piercing with inadequately disinfected equipment as well as medical interventions with inadequately disinfected equipment can also lead to infection.  The transmission rate through stored blood and blood coagulation preparations is now extremely low in the Western world.
•  Vaccination against hepatitis C virus is not yet possible.  However, major advances have been achieved in the development of drugs for treating chronic hepatitis C.
• Precautionary measures can also be taken in cases of inherited hemochromatosis (iron storage disease).  Long-term damages such as cirrhosis and liver cancer can be prevented if this disease is detected and treated early enough.  Early detection of this disease is therefore particularly important.  If you or any of your family members have this inherited disease, it is advisable for all primary relatives (parents, children, siblings) to be examined.  Genetic testing can determine whether they too are genetically predisposed to this disease.  Your doctor will inform you of further details.

Contact

Center of Interventional Hepatobiliary Medicine
Prof. Dr. med. Hans Scherübl
Vivantes Klinikum Am Urban
Academic Teaching Hospital of Charité, Berlin

Dieffenbachstraße 1
10967 Berlin
Tel: + 49 30 130 225201
Fax: + 49 30 130 225205
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
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