Liver cancer or hepatic cancer (from the Greek hēpar, meaning liver) is a cancer that originates in the liver. Liver tumors are discovered on medical imaging equipment (often by accident) or present themselves symptomatically as an abdominal mass, abdominal pain, yellow skin, nausea or liver dysfunction.
The leading cause of liver cancer is viral infection with hepatitis B virus or hepatitis C virus. The cancer usually forms secondary to cirrhosis caused by these viruses. For this reason, the highest rates of liver cancer occur where these viruses are endemic, including East-Asia and sub-Saharan Africa. Liver cancers should not be confused with liver metastases, also known as secondary liver cancer, which are cancers that originate from organs elsewhere in the body and migrate to the liver. They are formed from either the liver itself or from structures within the liver, including blood vessels or the bile duct. Five year survival rates are 17% in the United States.
Primary liver cancer is the sixth most frequent cancer globally and the second leading cause of cancer death. In 2012 it occurred in 782,000 people and resulted in 746,000 deaths.
Viral infection with either hepatitis C virus (HCV) or Hepatitis B virus (HBV) is the primary cause of liver cancer, accounting for 80% of hepatocellular carcinoma (HCC). The viruses cause HCC because massive inflammation, fibrosis and eventual cirrhosis occurs within the liver. HCC usually arises after cirrhosis, with an annual incidence of 1.7% in cirrhotic HCV-infected individuals. Around 5-10% of individuals that become infected with HBV become chronic carriers, and around 30% of these acquire chronic liver disease, which can lead to HCC. HBV infection is also linked to cholangiocarcinoma. The role of viruses other than HCV or HBV in liver cancer is much less clear, although there is some evidence that co-infection of HBV and hepatitis D virus may increase the risk of HCC.
Many genetic and epigenetic changes are formed in liver cells during HCV and HBV infection, which is a major factor in the production of the liver tumours. The viruses promote malignant characteristics of cells by altering gene methylation, affecting gene expression and promoting or repressing cellular signal transduction pathways. By doing this the viruses can prevent cells from undergoing a programmed form of cell death (apoptosis) and promote viral replication and persistence.
In addition to virus-related cirrhosis described above, other causes of cirrhosis can lead to HCC. Alcohol intake correlates with risk of HCC, and the risk is far greater in individuals with an alcohol-induced cirrhotic liver. There are a few disorders that are known cause cirrhosis and lead to cancer, including hereditary hemochromatosis and primary biliary cirrhosis.
Aflatoxin exposure can lead to the development of HCC. The aflatoxins are a group of chemicals produced by the fungi Aspergillus flavus (the name comes from A. flavus toxin) and A. parasiticus. Food contamination by the fungi leads to ingestion of the chemicals, which are very toxic to the liver. Common foodstuffs contaminated with the toxins are cereals, peanuts and other vegetables. Contamination of food is common in Africa, South-East Asia and China. HBV infection and aflatoxin exposure increases the risk to over three times that seen in HBV infected individuals without exposure. The mechanism by which aflatoxins cause cancer is through genetic mutation of a gene required for the prevention of cancer.
Other causes in adults
High grade dysplastic nodules are precancerous lesions of the liver. Within 2 years, there is a risk of cancer arising from these nodules of 30-40%.
Obesity has emerged as an important risk factor as it can lead to steatohepatitis.
Diabetes increases the risk of HCC.
Smoking increases the risk of HCC compared to non-smokers and previous smokers.
There is around 5-10% lifetime risk of cholangiocarcinoma in people with Primary sclerosing cholangitis.
Liver fluke infection increases the risk of cholangiocarcinoma, and is the reason Thailand has particularly high rates of this cancer.
Risk factors in children
Increased risk of liver cancer in children can be caused by Beckwith-Wiedemann Syndrome (associated with hepatoblastoma), familial adenomatous polyposis (associated with hepatoblastoma), low birth weight (associated with hepatoblastoma), Progressive familial intrahepatic cholestasis (associated with HCC) and Trisomy 18 (associated with hepatoblastoma).
Signs and symptoms
Because liver cancer is an umbrella term for many types of cancer, the signs and symptoms depend on what type of cancer is present. Cholangiocarcinoma is associated with sweating, jaundice, abdominal pain, weight loss and hepatomegaly. Hepatocellular carcinoma is associated with abdominal mass, abdominal pain, emesis, anemia, back pain, jaundice, itching, weight loss and fever.
Prevention of cancers can be separated into primary, secondary and tertiary prevention. Primary prevention preemptively reduces exposure to a risk factor for liver cancer. One of the most successful primary liver cancer preventions is vaccination against hepatitis B. Vaccination for hepatitis C virus is currently unavailable. Other forms of primary prevention are aimed at limiting transmission of these viruses by promotion of safe injection practice, screening of blood donation products and screening of high risk asymptomatic individuals. Aflatoxin exposure can be avoided by post-harvest intervention, which has been effective in west Africa. Reducing alcohol abuse, obesity, and diabetes would also reduce rates of liver cancer. Diet control in hemochromatosis could decrease the risk of iron overload, decreasing the risk of cancer.
Secondary prevention includes both cure of the agent involved in the formation of cancer (carcinogenesis) and the prevention of carcinogenesis if this is not possible. Cure of virus-infected individuals is not possible, but treatment with antiviral drugs such as interferon can decrease the risk of liver cancer. Chlorophyllin may have potential in reducing the effects of aflatoxin.
Tertiary prevention includes treatments to prevent the recurrence of liver cancer. These include the use of chemotherapy drugs, and antiviral drugs.
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