The liver is the largest internal organ, and is located just below the right lung, beneath the rib cage. It is crucial to many bodily functions. The liver:
Makes bile, essential to breaking down and absorbing food (particularly fats).
Breaks down alcohol, drugs, and wastes in the blood, facilitating excretion through urine or stool.
Makes most of the blood’s clotting factors.
Stores glycogen, which the body uses for energy.
About 2.2% of new cancer diagnoses each year are liver cancer, making it relatively uncommon, however while most cancers have become less deadly over time, liver cancer death rates have more than doubled since 1980.[1]
Men are nearly three times more likely to be diagnosed with liver cancer than women. The average age at diagnosis is 67, and diagnosis before the age of 45 is rare.
Early liver cancers rarely cause symptoms, but as the disease progresses, it may cause:
Jaundice
Fatigue / physical weakness
A hard lump beneath the right-side ribcage
Enlarged liver or spleen (felt as fullness beneath the right-side ribcage)
Easy bruising or bleeding
Itching
Enlarged veins on the belly that can be seen through the skin
Pain in the abdomen or near the right shoulder blade
Weight loss and loss of appetite
Nausea and vomiting
Swelling or fluid buildup in the abdomen
Pale, chalky stool and/or dark urine
Feeling of fullness after eating a small amount
Unexplained fever
Many of these symptoms may have other causes, and should be evaluated by a medical professional.
Different forms of liver cancer are characterized by distinct features and biological behaviors:
Hepatocellular carcinoma (HCC): This is by far the most common form of liver cancer in adults, and has several subtypes (though the specific subtype rarely affects treatment or prognosis). Many HCCs begin as a single tumor that only spreads late in its progression. In individuals with cirrhosis, cancer can also begin as many small tumors spread throughout the liver, instead of as a single larger tumor.
Fibrolamellar HCC: This subtype of HCC is very rare (making up less than 1% of all HCCs), and is most often found in women under the age of 35. Often, with this form of HCC, the majority of the liver is healthy, and the outlook is better than for other forms of the illness.
Intrahepatic cholangiocarcinoma: This form of cancer starts in the cells that line the small bile ducts that lead to the gallbladder (though most cancers of this type actually originate in the bile ducts outside the liver). Bile duct cancers usually have the same course of treatment as other liver cancers.
Angiosarcoma and hemangiosarcoma: These cancers form in blood cells lining the liver’s blood vessels, and are very rare. In this form of cancer, tumors grow quickly and are often difficult to treat.
Hepatoblastoma: This extremely rare form of cancer usually develops in children under the age of 4.
There are also benign tumors that can form in the liver. Some of these grow large enough to cause problems, but many require no treatment.
Liver cancer survival rates are based on how far the cancer has spread:
Localized: There is no sign the cancer has spread outside the liver.
Regional: The cancer has spread to nearby structures or lymph nodes.
Distant: The cancer has spread to distant parts of the body, such as the lungs or bones.
The 5-year survival rate for each stage is shown below:
Incidence
Below is the overall incidence of liver cancer by age group:
Risk Factors
There are several confirmed risk factors that contribute to an individual’s risk for liver cancer:
Smoking & secondhand smoke exposure: Smoking and secondhand smoke increase your risk of many cancers, including liver. Tobacco smoke contains numerous carcinogens that can lead to genetic mutations and uncontrolled cell growth, ultimately resulting in cancer. Quitting smoking at any age can significantly reduce the risk of cancer and other smoking-related diseases. The body begins to repair itself almost immediately after quitting, with the risk of cancer decreasing over time. Even individuals who have smoked for many years can benefit from quitting, as the risk decreases with each year of abstinence.
Alcohol use: Alcohol consumption, particularly heavy alcohol consumption, can lead to cirrhosis of the liver, a known risk for liver cancer. Even in the absence of cirrhosis, increased alcohol consumption correlates with an increased risk of liver cancer.
Health conditions: some text
Hepatitis B or C: Hepatitis B (HBV) and hepatitis C (HCV) are viruses that infect the liver, and infection can be either acute or chronic. In Asia and Africa, chronic HBV infection is the leading cause of liver cancer. In North America, Europe, and Japan, chronic HCV infection is the leading cause.
Cirrhosis: Usually the result of heavy alcohol use, or chronic HBV or HCV infection, cirrhosis–or scarring–of the liver increases the risk of liver cancer by a factor of 10 or more. Cirrhosis caused by chronic HCV infection carries the highest risk.
Type 2 diabetes: Individuals with type 2 diabetes have higher rates of liver cancer. This also seems to compound other risk factors, such as chronic HBV or HCV infection.
Non-alcoholic fatty liver disease (NAFLD): Common in obese individuals, non-alcoholic fatty liver disease is an accumulation of fat in the liver which leads to inflammation, a known risk factor for cancer.
Non-alcoholic steatohepatitis (NASH): This condition, the most severe form of NAFLD, can lead to inflammation or injury of the liver cells, as well as cirrhosis of the liver. Liver cancer risk is heightened in individuals with NASH even if it does not lead to cirrhosis.
Genetic conditions: Some liver cancers are likely caused by inherited genetic conditions. Conditions that increase one’s risk include: some text
Hemochromatosis
Wilson’s disease
Glycogen storage disease
Alpha-1 antitrypsin deficiency
Porphyria cutanea tarda
Tyrosinemia
Family history: A family history of liver cancer, even without a known hereditary cancer syndrome, increases one’s risk of developing liver cancer.
Oral contraceptive use: Several studies have shown a link between oral contraceptives and increased incidence of liver cancer.
Anabolic steroid use: Long-term use of anabolic steroids can increase the risk of developing liver cancer.
Diets high in red and processed meat or sugar-sweetened beverages: Red meat, processed meat, and sugar-sweetened beverages have all been shown to increase the incidence of liver cancer. Processed meats and sugar-sweetened beverages have also been tied to several other cancers and conditions such as type 2 diabetes that are known to increase cancer risk.
Chronic Aflatoxin B1 exposure: Aflatoxin B1 is produced by two forms of Aspergillus fungus that can grow on foods such as corn, groundnuts, tree nuts, grains, cereals, spices, cocoa beans, and dried fruits before or after harvest. A known carcinogen (and potentially lethal if consumed in large quantities), this mycotoxin is known to increase liver cancer risk. Purchasing foods that have been grown locally, and storing foods in dry, cool places, can help reduce your risk of exposure.
Protective Factors
Several factors have been shown to have protective effects against liver cancer:
Maintaining a healthy weight: Numerous studies have linked higher BMI to increased risk of various types of cancer, including liver cancer. Excess body fat can lead to higher levels of estrogen and insulin, as well as increased production of insulin-like growth factors. Higher BMI is also associated with chronic low-level inflammation, which can cause DNA damage over time and contribute to the development of cancer. Maintaining a healthy weight helps you to avoid this increased risk.
Physical activity: Regular exercise can reduce your risk of several types of cancer through a combination of physiological, hormonal, and immunological changes. It can reduce inflammation, improve immune function, improve hormonal regulation, and lower insulin levels. The American Cancer Society recommends engaging in at least 150 minutes of moderate activity or 75 minutes of vigorous activity each week. Furthermore, data indicates that individuals can see significant incremental benefit with additional exercise.
Fruit and vegetable consumption: Fruit and vegetables are rich in various nutrients which have been shown to have protective effects against multiple cancers, including liver. These foods contain a variety of antioxidants, which help neutralize free radicals in the body and reduce inflammation.
Oily fish consumption: Oily fish (such as salmon, mackerel, trout, sardines, and herring) are known to have various health benefits. Rich in omega-3 fatty acids, protein, vitamins, and minerals, studies have shown that eating oily fish has protective effects against several types of cancer, including liver, and that increased consumption increases these benefits.
NSAIDS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of medications commonly used to relieve pain, reduce inflammation, and lower fever, and they have also been shown to reduce liver cancer risk with regular use. In addition to their anti-inflammatory properties, NSAIDs have been shown to inhibit cell proliferation, induce programmed cell death, suppress tumor growth, and modulate immune responses. While NSAIDs have been associated with potential benefits in cancer prevention, their use is not without risks. Long-term or high-dose NSAID use has been linked to gastrointestinal bleeding, ulcers, and perforation. Additionally, certain NSAIDs have been associated with an increased risk of cardiovascular events such as heart attack and stroke.
Statins: Statins are a class of prescription drugs that lower cholesterol levels and can reduce the risk of heart attack and stroke, and studies have shown that statins may also lower the risk of several cancers, including liver. While the exact mechanism is unknown, this could be due to several factors. Statins have anti-inflammatory properties that may inhibit the inflammatory processes involved in cancer development and progression.
Coffee: Multiple studies have shown that coffee consumption has a protective effect against liver cancer. Drinking two or more cups daily can impart these benefits.
Screening
Early detection of liver cancer has a dramatic impact on prognosis. The 5-year survival rate for localized cancer is around 37.3%, but drops to just 3.3% once the cancer has spread to distant parts of the body.
Depending on your age and risk factors, the optimal liver cancer screening will vary:
Alpha-fetoprotein (AFP) blood testing: AFP is a protein that can be measured via blood tests. While this test is far from a perfect predictor of liver cancer (it can be elevated without cancer, or may not be elevated when cancer is present), it may help detect liver cancers earlier. This test is most often recommended for individuals at high risk of liver cancer (i.e., those with cirrhosis or chronic HBV or HCV infection). It is typically recommended in conjunction with abdominal ultrasound.
Ultrasound: These imaging tests can be used to detect liver cancer before symptoms begin. In high-risk individuals, doctors recommend ultrasounds every 6 months.
CT or MRI scans: These imaging tests can help find liver cancers, and can sometimes differentiate between benign and malignant liver tumors.
Other blood tests: Tests for liver function, blood clotting tests, and blood chemistry tests (which show whether certain substances are lower or higher than normal) can be early indicators of liver cancer or other liver problems. Abnormal results on these tests will likely lead to more targeted testing.
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