Hepatocellular Carcinoma Backgrounder EASL - European ...

BACKGROUND MEDIA INFORMATION
HEPATOCELLULAR CARCINOMA
What is hepatocellular carcinoma (HCC)
HCC is a cancer originating in liver cells and is one of the most common types of tumour. 1
Worldwide, HCC accounts for approximately 5.4% of all cancers 1 and causes 662,000 deaths per
year. 2 It is the fifth most common cause of cancer in men and the eighth most common cause in
women. 3 In China and Sub-Saharan Africa, HCC is the most common form of cancer. 4
What are the risk factors
The following causes of liver damage have been shown to increase the risk of HCC: 1
Viral hepatitis (persistent HCV/HBV infection)
Cirrhosis (alcohol, haemochromatosis, primary biliary cirrhosis)
Aflatoxin (a toxin produced by the Aspergillus fungus, a mould that grows on food stored
incorrectly, usually seen in Southern Asia and Sub-Saharan Africa)
Parasite infections (seen in some areas of Southern Asia and Sub-Saharan Africa)
It is often difficult to determine HCC’s exact cause since it can occur 20-30 years after the liver
injury (such as hepatitis infection).
HCC is so prevalent in Sub-Saharan Africa and Southeast Asia due to high rates of HCV and HBV
infection. 1 In western countries, alcoholism and viral hepatitis are the leading causes of cirrhosis
and subsequent HCC. 5
What are the symptoms
Symptoms of liver cancer are often vague and may include the following: 6
Fatigue
Weight loss
Poor appetite
Abdominal pain or discomfort
Jaundice (yellowing of the eyes and skin)

How is HCC diagnosed 6
Liver disease cannot be diagnosed by routine blood tests. Most patients with liver cancer have
associated liver disease (such as cirrhosis) and, therefore, their liver blood tests may not be
normal, even when cancer is not present.
The most widely used specialised blood test for diagnosing HCC is alpha-fetoprotein (AFP). This is
a protein normally formed by liver cells in the foetus. High levels of this protein in adult blood can
be indicative of liver cancer. However, increased levels of AFP can also be seen in patients with
chronic hepatitis and other types of liver disease, even without cancer. Additionally, a considerable
number of HCCs develop in the absence of changes in AFP levels.
A number of different medical imaging techniques can be also used to aid diagnosis. Ultrasound
examination is usually the first technique used if a doctor suspects liver cancer. Using this
technique, the internal organs can be viewed on a screen and abnormalities detected. A
computerised axial tomography (CT scan) is also commonly used where pictures are taken of thin
sections of the body as it moves through the CT scanner. Magnetic resonance imaging (MRI) is
another type of scan that can provide very clear images of internal organs.
Sometimes a liver biopsy is performed, where a small sample of liver is obtained through a very
fine needle. The sample is then studied under a microscope to determine whether the cells are
cancerous.
How is HCC treated
Surgery may be an option if tumours within the liver are small, although the cancer is likely to recur
in 50-60% of patients. Unfortunately, due to extensive disease or poor liver function, only 10-20%
of patients are suitable for surgery. 7
For some, a liver transplant may be the only option. Following a successful transplantation, 75-
80% of patients will survive for more than five years. 8
Systemic therapies, such as cytotoxic chemotherapies or hormonal compounds, have not shown
any survival benefit in advanced HCC. 9
The current standard of treatment in HCC is the multikinase inhibitor sorafenib, which has proven
survival benefit in patients with advanced HCC. 9
Hepatocarcinogenesis is a complex process involving different pathways. Novel inhibitors targeting
these important signalling pathways to stop the progression of the carcinogenesis are currently
being studied in clinical trials (phase I to III). The data from these studies will establish the
substances’ potential in mono- and combination-therapy for HCC. 9

What is the long-term prognosis
Prognosis is usually poor because only 10-20% of cancers are suitable for surgery. If the cancer
cannot be completely removed, the disease may be fatal within three to six months. 10
Can HCC be prevented
Although currently one of the most common worldwide causes of cancer death, the incidence of
HCC could be reduced through vaccination against HBV virus, screening and treatment for HCV
infections and reduction of alcoholic liver disease. 1 However, because the latency period between
hepatic damage and the development of HCC is so long, it may be many years before HCC
incidence decreases from these interventions.
References
1 Kumar Vinay, Nelso Fausto and Abul Abbas. Robbins & Cotran Pathologic Basis of Disease, Seventh
Edition. Saunders; 2004.
2 Cancer fact sheet. World Health Organisation. February 2006.
http://www.who.int/mediacentre/factsheets/fs297/en/ accessed 19.03.10
3 Weber S, et al. Liver and bile duct cancer. In Abeloff MD, et al. Clinical Oncology. 3rd ed. Philadelphia, Pa.:
Saunders Elsevier; 2004:1981-2011.
4 WHO Disease and injury country estimates". World Health Organization. 2009.
http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved Nov. 11, 2009.
5 Nguyen T et al. Alcohol abuse and chronic hepatitis C. Current Hepatitis Reports. 2007. 6; 3: 119-124.
6 Liver Cancer. Medicine Net. Available at http://www.medicinenet.com/liver_cancer/page5.htm accessed
19.03.10
7 Hepatocellular Carcinoma. Wikipedia. Available at http://en.wikipedia.org/wiki/Hepatocellular_carcinoma
accessed 29.03.10
8 Liver transplant. NHS Clinical Knowledge Summary. Available at
http://www.cks.nhs.uk/patient_information_leaflet/liver_transplant# accessed 29.03.10
9 Worns M A et al. Novel inhibitors in development for hepatocellular carcinoma. Expert Opin. Investig.Drugs (2010)
19(5)
10 Hepatocellular Carcinoma. Medline Plus. Available at
http://www.nlm.nih.gov/medlineplus/ency/article/000280.htm accessed 19.03.10