Liver cancer is the sixth most common cancer worldwide. Almost two-thirds of all liver cancer cases occur in men, approximately 80% of which are 60 years of age or older. Liver cancer is broadly categorized as primary and secondary.
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Primary liver cancer
Primary liver cancer originates in the liver, with its different forms named after the types of cells that the cancer has developed from. The two main types of primary liver cancer include hepatocellular carcinoma (HCC) or hepatoma, and biliary tree cancer.
HCC, which is the most prevalent primary liver cancer, affects the hepatocytes, which are the primary cells that constitute the liver. Normally HCC is confined to the liver. however, it may metastasize and spread to other organs.
The main risk factors for HCC include liver cirrhosis, coinfection with viruses, non-alcoholic steatohepatitis (NASH), obesity and type 2 diabetes, as well as heavy smoking, prolonged use of anabolic steroids, inherited metabolic diseases, and several other rare diseases.
Cirrhosis of the liver
Approximately 3-4% of people with liver cirrhosis will go on to develop HCC each year. Cirrhosis occurs when the liver has become scarred as a result of damage over a long period of time. Therefore, any disease that causes cirrhosis can potentially lead to HCC, although certain causes of cirrhosis have a particularly strong link with HCC.
Coinfection with viruses
Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is the worldwide leading cause for HCC. These infections lead to cirrhosis of the liver and are responsible for making liver cancer the most prevalent cancer in many parts of the world.
NASH is a form of liver inflammation and damage that occurs due to the accumulation of fat in the liver. Moreover, NASH is a member of a group of conditions called non-alcoholic fatty liver disease and is similar to the kind of liver disease that results from long-term alcohol abuse.
While symptoms and problems are uncommon in many people with NASH, the presence of symptoms indicates that liver function is compromised, which can possibly lead to cirrhosis.
Obesity and type 2 diabetes
Both obesity and type 2 diabetes are associated with a higher risk of developing HCC, even more so if both are present.
Heavy smoking has been linked with HCC, particularly when present alongside excessive alcohol consumption or infection with viral hepatitis.
Prolonged use of anabolic steroids may lead to the development of liver tumors. These tumors are usually benign; however, they can grow and rupture, which can cause pain.
Inherited metabolic and other rare diseases
People with hereditary hemochromatosis absorb too much iron from ingested food. The iron settles in tissues throughout the body, including the liver. If enough iron accumulates in the liver, it can lead to cirrhosis and increase the risk of developing liver cancer.
Other rare diseases that may lead to HCC include tyrosinemia, porphyria cutanea tarda, glycogen storage diseases, and Wilson’s disease, to name a few.
Biliary tree cancer
Cholangiocarcinoma (bile duct cancer) is a rare but aggressive form of liver cancer that starts in the cells that line the bile duct. Unlike HCC, this form of primary cancer is more common in women than in men.
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In most cases, there is no clear reason why cholangiocarcinoma develops; however, people suffering from the following problems are at a higher risk of developing this form of liver cancer:
- Cirrhosis of the liver – As is the case with HCC, this scarring due to disease (e.g., HCV, HBV) and irritants (e.g., alcohol) can predispose a person to cholangiocarcinoma.
- Primary sclerosing cholangitis (PSC) – PSC is characterized by inflammation of the bile ducts (cholangitis) leading to scar tissue (sclerosis) formation. The cause of the inflammation is not usually known but the risk of this is increased by smoking.
- Bile duct stones – Bile duct stones can cause chronic inflammation that increases the risk of bile duct cancer.
- Rare diseases - Certain rare diseases like Caroli syndrome and polycystic liver disease can increase an individual's risk of cholangiocarcinoma.
Fibrolamellar carcinoma is a rare variation of HCC that is usually found in people between 20 to 40 years of age without cirrhosis being present. Fortunately, this form of liver cancer is usually well contained and can be removed with surgery.
Secondary liver cancer
Also known as metastatic cancer, secondary liver cancer form occurs due to cancer that first develops elsewhere in the body that then spreads through a process known as metastasis to the liver. The liver may be susceptible to this because it filters the blood; therefore, cancer cells in the bloodstream have a high chance of accumulating in the liver to establish a malignant tumor.
Those who are most at risk of secondary liver cancer are those with cancers of the large colon, pancreas, stomach, lung, or breast.