June 2013 

Liver cancer—risk factors, screening and treatment options

Risk factors

Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is linked to an increased risk for liver cancer. However, there are also other factors that can heighten the risk for liver cancer by directly or indirectly inciting the growth of abnormal cells and their transformation into tumours in the liver. Studies in the U.S. and northern Europe have found that liver cancer has developed in people without hepatitis viruses who had the following risk factors:


In excessive amounts this substance damages liver cells. Over time, with continued excessive intake of alcohol, liver damage becomes more severe and healthy tissue is replaced with scarred tissue in the liver. Eventually, severe liver damage (cirrhosis) occurs. In such cases, sometimes damaged liver cells can transform and become pre-cancers or cancers.

Smoking tobacco

Tobacco smoke contains thousands of chemicals, some of which cause cancer. The elevated cancer risk from tobacco use not only affects the lungs and throat but also the liver.

Type 2 diabetes

The pancreas gland produces insulin. This hormone helps cells to absorb sugar (glucose) from the blood. Due to poor diet, insufficient exercise and perhaps aging, the body can gradually lose its sensitivity to the effects of insulin. This loss of sensitivity is called insulin resistance. If left unmanaged, insulin resistance grows worse and causes the pancreas gland to produce ever-greater amounts of insulin in an attempt to compensate. Eventually, insulin resistance becomes so severe that type 2 diabetes occurs.

Many complications can accompany type 2 diabetes, including kidney dysfunction, nerve damage, a somewhat weakened immune system, excess production of insulin, a rise in inflammation and general weight gain. In addition, the liver stores more fat and becomes enlarged. Increased inflammation and higher-than-normal levels of insulin are both factors that are associated with  an elevated risk of cancer in general and liver cancer in particular.

A fatty damaged liver that is subjected to increased levels of inflammation and stimulation from cancer-causing chemicals in tobacco smoke, excess insulin and harmful proteins from HCV might have cells that are more easily transformed into abnormal paths of development, such as pre-cancer and cancer.

Liver cancer symptoms

In the early stages of liver cancer, people may not have symptoms. However, as the tumour(s) grow, they can cause complications and symptoms such as the following can appear:

  • abdominal pain
  • loss of appetite
  • unintentional weight loss
  • abdominal swelling
  • nausea
  • fever
  • weakness
  • yellowing of the skin and whites of the eyes (jaundice)

Most of these symptoms are similar to those seen in people with other illnesses, so on their own they do not prove the presence of liver cancer. This is why medical investigation is necessary.

Uncovering the tumour(s)

As part of the investigation of these symptoms in people at high risk for liver cancer, doctors may order laboratory testing of blood for the presence of different proteins (tumour markers) associated with cancer. However, no single test is perfect and research is being done to try to find better tumour markers. Here are some markers that may be used; bear in mind that liver and cancer specialists may use other tests:

  • AFP (alpha-fetoprotein) – In adults, elevated levels of this protein can be suggestive of cancer of the liver or other organs. AFP is produced by tumours and levels generally rise in some cancers. However, in the early stages of development, tumours may not produce much AFP, so this test is not highly specific or always reliable when screening for liver cancer.
  • AFP-L3 (Lens culinaris agglutinin reactive fraction of AFP) – Some doctors have found this molecule to be more useful than AFP when screening patients for liver cancer.
  • DCP (des-gamma-carboxy-prothrombin) – This protein is found in elevated quantities in about 80% of people who have liver cancer. However, elevated DCP levels can also occur because of a deficiency of vitamin K and in people who use the blood-thinning drug Coumadin.


Ultrasound scans of the liver are very useful because they can detect growths. If ultrasound scans are suggestive of tumours, further scans such as those done with high-resolution X-rays (a CT scan) can be used. An MRI (magnetic resonance imaging) can help to provide detailed images of a tumour and its impact on blood vessels and adjacent parts of the liver.

Dealing with the tumour

Here are several possibilities:

  • surgery
  • radiofrequency ablation (use of an electrical current to heat and destroy the tumour): For this procedure, a needle is inserted into the tumour and an electrical current produces intense heat, which kills the cancer cells.
  • injecting the tumour with alcohol: This kills the cancer cells but also destroys nearby normal tissue. Usually multiple injections are required and this form of therapy works best with relatively small tumours.
  • local chemotherapy: Injections of chemotherapy into the artery that supplies blood to the liver can sometimes work when tumours have not spread beyond the liver.
  • liver transplantation

Newer therapies such as sorafenib (Nexavar) have produced very modest results—extending survival by several months. Furthermore, sorafenib does not appear to provide significant benefit in people of Asian ethnicity. There are several experimental liver cancer therapies being tested in clinical trials. In some cases, it may be useful to have a discussion with a cancer specialist when weighing options about such therapy.

—Sean R. Hosein


  1. Canadian Cancer Society’s Steering Committee on Cancer Statistics. Canadian Cancer Statistics 2013. Toronto, ON: Canadian Cancer Society; 2013.
  2. Carr BI. Chapter 92. Tumors of the Liver and Biliary Tree. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.