Your liver is the largest organ in your abdomen (and the largest internal organ in your body). It’s not only big in size, but also in importance—the liver performs vital functions, like removing waste and filtering out toxins (including alcohol) from the blood. It also secretes bile and enzymes that allow the body to digest food and extract its nutrients, among other things. In essence, the liver controls the body’s metabolism and homeostasis.

The National Cancer Institute estimates that over 42,000 people will be diagnosed with liver cancer this year. What’s more, the number of cases is rising: Since 1980, the incidence of liver cancer has increased more than threefold. Liver cancer can affect people of any age, but it is most common in people over age 55.

People at the highest risk for liver cancer are those with cirrhosis, or scarring of the liver, a condition that can be caused by heavy alcohol use, viral hepatitis, and non-alcoholic fatty liver disease.

“It’s important to know that most liver diseases, which can lead to liver cancer, are treatable,” says Yale Medicine’s Mario Strazzabosco, MD, director of the Liver Cancer Program at Smilow Cancer Hospital. “Also, many cases of hepatocellular carcinoma [HCC], the most common type of primary liver cancer, can be diagnosed early if high-risk patients are closely monitored by their doctor. There is a lot we can do for patients diagnosed at an early stage, and some patients can be cured.”

Liver cancer develops when cells in the liver grow and divide uncontrollably. Over time, these cells can form tumors. Often, tumors are benign, meaning they are non-cancerous and cannot spread to other parts of the body. Sometimes, though, tumors are cancerous, or malignant. The cells that make up malignant tumors are capable of invading nearby tissues and spreading to other parts of the body.

To better understand and properly treat liver cancer, doctors will need to know whether the cancer is primary (meaning it started in the liver) or secondary (or metastatic, meaning it is cancer that began in another part of the body and spread to the liver).

Primary liver cancer. Cancer that originates in the liver is called primary liver cancer. There are several types of primary liver cancer, including:

• Hepatocellular carcinoma (HCC). HCC accounts for around 80% to 90% of all primary liver cancer diagnoses. The vast majority of people who develop HCC have cirrhosis.
• Bile duct cancer. Also known as cholangiocarcinoma, this type of cancer begins in cells found in the bile ducts, which are tubes that transport bile from the liver and gallbladder to the small intestine. This is the second most common type of primary liver cancer. Cancer can affect different parts of the bile duct. Cancer that occurs in bile ducts within the liver is known as intrahepatic bile duct cancer. When cancer occurs in the bile ducts outside the liver, it is called extrahepatic bile duct cancer.
  
• Angiosarcoma. This rare form of cancer accounts for about 2% of primary liver cancer cases.
• Hepatoblastoma (HB). This is the most common type of primary liver cancer in children. About nine out of every ten cases of HB occur in children under 5 years of age.

Secondary liver cancer. Secondary (or metastatic) liver cancer occurs when cancer spreads to the liver from another part of the body. Several types of cancer are known to spread to the liver, including leukemia and lymphoma, as well as cancers of the lungs, breasts, pancreas, large intestine, and stomach. Secondary liver cancer is more common than primary liver cancer.

When secondary liver cancer develops, the new growth contains the same type of cancer cells as the primary tumor. So, if lung cancer spreads to the liver, the liver tumor will contain cells that are similar to lung cancer cells, not liver cancer cells. The cancer is also named according to the primary tumor. For instance, lung cancer that spreads to the liver may be referred to as metastatic lung cancer to the liver.

Several factors are associated with increased risk of developing primary liver cancer. These include:

• Cirrhosis (around 90% of people with HCC in the U.S. have cirrhosis)
• Hepatitis B or C infection
• Heavy alcohol use
• Non-alcoholic fatty liver disease (NAFLD) (especially a type of NAFLD called non-alcoholic steatohepatitis, or NASH)
• Obesity
• Tobacco use
• Diabetes
• Family history of liver cancer
• Exposure to aflatoxin (a fungus found on some agricultural crops)
• Age
• Male sex (men are at higher risk than women) 
• Certain inherited or rare disorders, including hereditary hemochromatosis, alpha-1 antitrypsin deficiency, porphyria cutanea tarda, primary sclerosing cholangitis (PSC), Wilson disease, and glycogen storage disease, among others

Patients with known risk factors should discuss with their physician the best surveillance protocol. It is important to note that liver cancer can also occur in patients without cirrhosis.

Symptoms of liver cancer may not occur until the disease has reached an advanced stage. When symptoms are present, they can include:

• Unintentional weight loss
• Loss of appetite or feeling full after eating small meals
• Nausea and vomiting
• Easy bruising or bleeding
• Yellowing of the skin and eyes (known as jaundice)
• Abdominal pain (especially on the upper right side, where the liver is located)
• Lump on the right side of the abdomen
• Pain in the right shoulder
• Abdominal swelling
• Ankle swelling
• Fatigue
• Fever
• Itchy skin

To diagnose liver cancer, the doctor, usually a liver specialist (called a hepatologist), will ask about your medical history, identify risk factors and symptoms, and perform a physical exam. Imaging tests, such as an ultrasound, a computed tomography (CT) scan, or a magnetic resonance imaging (MRI) study, may also be done. Blood work to check liver function and to measure the levels of certain substances, such as alpha-fetoprotein, or AFP (high levels of AFP may indicate liver cancer), may also be necessary.

In some cases, diagnosis requires a biopsy. In this procedure, a doctor removes a small piece of liver tissue, and a pathologist examines it under a microscope for the presence of cancer cells. Tissue may be biopsied using a needle that’s guided by ultrasound, MRI, or CT—or by using a laparoscope, a thin tube equipped with a camera and surgical instruments that is inserted through a small incision in the abdomen.

A number of therapies are used to treat liver cancer. Choice of treatment depends on several factors, such as the type and stage of the cancer, and the patient’s overall health and liver function. 

Treatments for liver cancer include:

• Surgery. Surgery may be performed to remove part of the liver. This procedure, known as a partial hepatectomy, is used to treat cancer that is localized to one part of the liver. The liver can regenerate tissue removed during surgery.
• Liver transplant. In this procedure, the patient’s liver is surgically removed and replaced with a healthy liver from a donor. To be eligible for a transplant, the cancer must meet certain criteria regarding tumor size and number.
• Ablation therapy. Ablation treatments destroy cancer cells by exposing them to high-energy radio waves, electromagnetic waves, heat, cold, or ethanol. In ablative procedures, an interventional radiologist inserts a small, needle-like probe directly into the tumor using live image guidance. The treatment is delivered to the tumor using the probe.
• Embolization therapy (trans-arterial embolization, TAE). In embolization therapy, an interventional radiologist inserts a catheter into an artery (often in the groin), maneuvers it to the hepatic artery in the liver, and injects a substance into the hepatic artery that reduces or blocks blood flow to the tumor. This kills cancer cells by starving them of nutrients and oxygen. Sometimes, a doctor will also inject chemotherapy drugs or tiny, radiation-containing beads into the artery. Known respectively as trans-arterial chemoembolization (TACE) and radioembolization (RE), the drugs and radiation help destroy more cancer cells.
• Radiation therapy. This treatment kills and damages cancer cells by exposing them to radiation. External beam radiation therapy (EBRT) is given by directing it at the cancer with a machine located outside the body. Another technique, called stereotactic body radiation therapy (SBRT), precisely delivers high doses of radiation to tumors. It is used to treat small tumors and usually requires fewer treatment sessions than EBRT.
• Targeted therapy. This therapy uses drugs that are designed to target specific components of cancer cells that are not found in normal, healthy cells.
• Immunotherapy. Immunotherapy drugs stimulate or suppress the patient’s own immune system, so that it is better able to fight cancer.

For people who have secondary liver cancer, doctors will also need to treat the underlying cancer. They may use chemotherapy to treat cancer that has spread to the liver.

The outlook depends on several factors, including the patient's age and general health, as well as the stage of the cancer and the timing of diagnosis. In general, cancers that are caught at an early stage are easiest to treat and have the best outcomes. Often, early-stage liver cancer can be cured. After completing treatment, people may need to continue to take medications for their liver and should see their doctor regularly to monitor their health—and to keep an eye on possible recurrence of the cancer.

Every liver cancer case is discussed by a multi-specialist team at a weekly meeting (called a tumor board) to ensure each patient receives the best individualized treatment possible, Dr. Strazzabosco says. 

“The benefit of the Liver Cancer Program is that we are truly a multidisciplinary team, offering personalized care for our patients,” he says. “The program has a number of specialists—hepatologists, medical oncologists, interventional radiologists, surgeons, and palliative care doctors—each providing high-level and highly scientific care.

It is important that patients are referred to a center that can offer all kinds of treatments, he adds. “After treatment, the patient remains at risk for liver function deterioration and tumor recurrence. A distinctive feature of our center is that it offers continuative, long-term hepatological follow-up and surveillance for tumor recurrence,” he says.