Hepatocellular Carcinoma (Primary Liver Cancer)

 

 

Primary liver cancer, also known as hepatocellular carcinoma, is a cancer that begins in the liver.. Each year in the United States, approximately 15,000 men and 6,000 women are diagnosed with primary liver cancer. 

 

The liver is also the most common site to which cancer has spread (metastasized) from other parts for the body, most commonly the colon, lungs, or breast. When this happens, it is NOT liver cancer. Instead, the cancer is named for the organ it originated from (the primary site). For example, colon cancer that spreads to the liver is called metastatic colon cancer. It is not liver cancer. In the U.S., metastatic cancer in the liver is far more common than primary liver cancer.

 

Liver Anatomy and Function

 

The liver is a vital organ, meaning that one cannot live without it. The liver serves many critical functions including metabolism of drugs and toxins, removing degradation products of normal body metabolism (for example clearance of ammonia and bilirubin from the blood), and synthesis of many important proteins and enzymes (such as factors necessary for blood to clot).

 

•  The liver is the largest organ inside your abdomen. It is found behind your ribs on the right side of your body.

• The liver does important work to keep the patient healthy:

• It removes harmful substances from the blood.

• It makes enzymes and bile that help digest food.

• It also converts food into substances needed for life and growth.

• The liver gets its supply of blood from two vessels. Most of its blood comes from the hepatic portal vein. The rest comes from the hepatic artery.

 

About Cancer Cells

 

Cancer begins in cells, the building blocks that make up tissues. Tissues make up the organs of the body. Normal cells grow and divide to form new cells as the body needs them. When normal cells grow old or get damaged, they die, and new cells take their place. Sometimes, this process goes wrong. New cells form when the body doesn't need them, and old or damaged cells don't die as they should. The buildup of extra cells often forms a mass of tissue called a growth, nodule, or tumor.

 

Tumors in the liver can be benign (not cancer) or malignant (cancer). 

 

Benign Tumors

• are rarely a threat to life

• can be removed and usually don't grow back

• don't invade the tissues around them

• don't spread to other parts of the body

 

Malignant Tumors

• may be a threat to life

• sometimes can be removed but can grow back

• can invade and damage nearby tissues and organs (such as the stomach or intestine)

• can spread to other parts of the body

 

Hepatocellular Carcinoma

Most primary liver cancers begin in hepatocytes (liver cells). This type of cancer is called hepatocellular carcinoma or malignant hepatoma. Liver cancer cells can spread by breaking away from the original tumor. They mainly spread by entering blood vessels, but liver cancer cells can also be found in lymph nodes. The cancer cells may attach to other tissues and grow to form new tumors that may damage those tissues. See the Staging section for information about liver cancer that has spread.

 

 

Risk Factors

 

The more risk factors a patient has, the greater the chance that liver cancer will develop. Studies have found the following risk factors for liver cancer:

 

• Infection with hepatitis B virus (HBV) or hepatitis C virus (HCV): Liver cancer can develop after many years of infection with either of these viruses. Around the world, infection with HBV or HCV is the main cause of liver cancer.

• HBV and HCV can be passed from patient to patient through blood (such as by sharing needles) or sexual contact. An infant may catch these viruses from an infected mother. Although HBV and HCV infections are contagious diseases, liver cancer is not. The patient can't catch liver cancer from another patient.

• HBV and HCV infections may not cause symptoms, but blood tests can show whether either virus is present. If so, the doctor may suggest treatment. Also, the doctor may discuss ways to avoid infecting other patients.

• In patients who are not already infected with HBV, hepatitis B vaccine can prevent HBV infection. Researchers are working to develop a vaccine to prevent HCV infection.

• Heavy alcohol use: Having more than two drinks of alcohol each day for many years increases the risk of liver cancer and certain other cancers. The risk increases with the amount of alcohol that a patient drinks.

• Aflatoxin: Liver cancer can be caused by aflatoxin, a harmful substance made by certain types of mold. Aflatoxin can form on peanuts, corn, and other nuts and grains. In parts of Asia and Africa, levels of aflatoxin are high. However, the United States has safety measures limiting aflatoxin in the food supply.

• Iron storage disease: Liver cancer may develop among patients with a disease that causes the body to store too much iron in the liver and other organs.

• Cirrhosis: Cirrhosis is a serious disease that develops when liver cells are damaged and replaced with scar tissue. Many exposures cause cirrhosis, including HBV or HCV infection, heavy alcohol use, too much iron stored in the liver, certain drugs, and certain parasites. Almost all cases of liver cancer in the United States occur in patients who first had cirrhosis, usually resulting from hepatitis B or C infection, or from heavy alcohol use.

• Obesity and diabetes: Studies have shown that obesity and diabetes may be important risk factors for liver cancer.

 

Symptoms

 

Early liver cancer often doesn't cause symptoms. When the cancer grows larger, one or more of these common symptoms may occur:

 

• Pain in the upper abdomen on the right side

• A lump or a feeling of heaviness in the upper abdomen

• Swollen abdomen (bloating)

• Loss of appetite and feelings of fullness

• Weight loss

• Weakness or feeling very tired

• Nausea and vomiting

• Yellow skin and eyes, pale stools, and dark urine from jaundice

• Fever

 

These symptoms may be caused by liver cancer or by other health problems. With any of these symptoms, a doctor should be consulted so that problems can be diagnosed and treated as early as possible.

 

Diagnosis

 

The following tests are used to diagnose liver cancer:

 

• Physical exam: Your doctor feels your abdomen to check the liver, spleen, and other nearby organs for any lumps or changes in their shape or size. Your doctor also checks for ascites, an abnormal buildup of fluid in the abdomen. Also, your skin and eyes may be checked for signs of jaundice.

• Blood tests: Many blood tests may be used to check for liver problems. One blood test detects alpha-fetoprotein (AFP). High AFP levels could be a sign of liver cancer. Other blood tests can show how well the liver is working.

• CT scan: An x-ray machine linked to a computer takes a series of detailed pictures of your liver and other organs and blood vessels in your abdomen. The patient may receive an injection of contrast material so that your liver shows up clearly in the pictures. On the CT scan, your doctor may see tumors in the liver or elsewhere in the abdomen.

• MRI: A large machine with a strong magnet linked to a computer is used to make detailed pictures of areas inside your body. Sometimes contrast material makes abnormal areas show up more clearly on the picture.

• Ultrasound test: The ultrasound device uses sound waves that can't be heard by humans. The sound waves produce a pattern of echoes as they bounce off internal organs. The echoes create a picture (sonogram) of your liver and other organs in the abdomen. Tumors may produce echoes that are different from the echoes made by healthy tissues.

• Biopsy: A biopsy is usually not needed to diagnose liver cancer, but in some cases, the doctor may remove a sample of tissue. A pathologist uses a microscope to look for cancer cells in the tissue. Tissue can be obtained through several methods:

  • A needle through the skin: The doctor inserts a thin needle into the liver to remove a small amount of tissue. CT or ultrasound may be used to guide the needle. The most common risk of a needle biopsy is bleeding, especially because liver cancer is a tumor that has many blood vessels (vascular). Rarely, new small areas of tumor can be seeded from the tumor into the liver along the needle track.

  • Laparoscopic Surgical Procedure: The surgeon makes a few small incisions in your abdomen. A thin, lighted tube (laparoscope) is inserted through the incision. The laparoscope has a tool to remove tissue from the liver.

  • Open Surgical Procedure: The surgeon can remove tissue from the liver through a large incision

 

Staging

 

If liver cancer is diagnosed, the doctor needs to learn the extent (stage) of the disease to help determine the optimal treatment. Staging is an attempt to find out whether the cancer has spread, and if so, to what parts of the body.

When liver cancer spreads, the cancer cells may be found in the lungs. Cancer cells also may be found in the bones and in lymph nodes near the liver.

 

When cancer spreads from its original place to another part of the body, the new tumor has the same kind of abnormal cells and the same name as the primary tumor. For example, if liver cancer spreads to the bones, the cancer cells in the bones are actually liver cancer cells. The disease is metastatic liver cancer, not bone cancer. It's treated as liver cancer, not bone cancer. Doctors sometimes call the new tumor "distant" or metastatic disease.

 

To learn whether the liver cancer has spread, one or more of the following tests may be used:

 

• CT scan (CAT scan) of the Chest: A CT scan often can show whether liver cancer has spread to the lungs. A CT scan procedure that makes a series of detailed pictures of areas inside the body, such as the chest, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

• Bone scan: The doctor injects a small amount of a radioactive substance into your blood vessel. It travels through the bloodstream and collects in the bones. A machine called a scanner detects and measures the radiation. The scanner makes pictures of the bones. The pictures may show cancer that has spread to the bones.

 

Treatment

 

Treatment options for  liver cancer are surgery (including a liver transplant), ablation, embolization, targeted therapy, radiation therapy, and chemotherapy. A combination of these treatments may be used.

The appropriate treatment depends on the following:

 

• the number, size, and location of tumors in your liver

• how well your liver is working and whether the patient have cirrhosis

• whether the cancer has spread outside your liver

• the patient's age and general health including the ability to handle potential side effects

 

At this time, liver cancer can be cured only when found at an early stage (before it has spread) and removed surgically. For patients who are not surgical candidates, other treatments are available. Patients with liver cancer may also consider enrolling in a clinical trial. These are research studies testing new treatments and are an important option for patients with all stages of liver cancer.

 

Specialists who treat liver cancer include transplant and hepatobiliary surgeons, surgical oncologists, gastroenterologists, medical oncologists, and radiation oncologists. The healthcare team also includes an oncology nurse and a registered dietitian.

 

 

Surgery

 

Liver Resection

Surgery is an option for patients with an early stage of liver cancer. The surgeon may remove the whole liver or only the part that has cancer. If the whole liver is removed, it's replaced with healthy liver tissue from a donor.

A liver resection is the removal of part of the liver. Surgery to remove part of the liver is also called a partial hepatectomy. A patient with liver cancer may have part of the liver removed if lab tests show that the liver is working well and if there is no evidence that the cancer has spread to nearby lymph nodes or to other parts of the body.

The surgeon removes the tumor along with a margin of normal liver tissue around the tumor. The extent of the surgery depends on the size, number, and location of the tumors. It also depends on how well the liver is working.

 

As much as 80 percent of the liver may be removed. The surgeon leaves behind normal liver tissue. The remaining healthy tissue takes over the work of the liver. Also, the liver can regrow the missing part. The new cells grow over several weeks.

 

It takes time to heal after surgery, and the time needed to recover is different for each patient. The patient may have pain or discomfort for the first few days. Medicine can help control your pain. Before surgery, the patient should discuss the plan for pain relief with your doctor or nurse. After surgery, your doctor can adjust the plan if the patient need more pain control.

It's common of a patient to feel tired or weak for a while. Also, the patient may have diarrhea and a feeling of fullness in the abdomen.

 

The health care team will watch the patient for signs of bleeding, infection, liver failure, or other problems.

 

 

Liver Transplant

A liver transplant is an option if the tumors are small, the disease has not spread outside the liver, and suitable donated liver tissue can be found.

Donated liver tissue comes from a deceased patient or a live donor. If the donor is living, the tissue is part of a liver, rather than a whole liver.

While the patient wait for donated liver tissue to become available, the health care team monitors your health and provides other treatments.

 

 

When healthy liver tissue from a donor is available, the transplant surgeon removes your entire liver (total hepatectomy) and replaces it with the donated tissue. After surgery, your health care team will give the patient medicine to help control your pain. The patient may need to stay in the hospital for several weeks. During that time, your health care team monitors how well your body is accepting the new liver tissue. The patient'll take medicine to prevent your body's immune system from rejecting the new liver. These drugs may cause puffiness in your face, high blood pressure, or an increase in body hair.

 

 

Other Procedures and Treatments

 

 

Ablation

Methods of ablation destroy the cancer in the liver. They are treatments to control liver cancer and extend life. They may be used for patients waiting for a liver transplant. Or they may be used for patients who can't have surgery or a liver transplant. Surgery to remove the tumor may not be possible because of cirrhosis or other conditions that cause poor liver function, the location of the tumor within the liver, or other health problems.

 

 

Methods of ablation include the following:

 

 

• Radiofrequency ablation ( RFA) is the destruction of tumors with heat from radiofrequency waves. The doctor uses a special probe that contains tiny electrodes to kill the cancer cells with heat. Ultrasound, CT, or MRI may be used to guide the probe to the tumor. Usually, the doctor can insert the probe directly through your skin, and only local anesthesia is needed. Sometimes, surgery under general anesthesia is needed. The doctor inserts the probe through a small incision in your abdomen (using a laparoscope) or through a wider incision that opens your abdomen. Some patients have pain or a slight fever after this procedure. Staying overnight in the hospital is not usually needed.

• Laser Albation

• Microwave ablation, used less frequently than RFA, destroys liver tumors using heat generated by microwave energy. The surgeon inserts a small laparoscopic port or open incision to access the tumor. A CT scan or ultrasonic guidance is used to pinpoint the exact location of the tumor. A thin antenna, which emits microwaves, is then inserted into the tumor. This produces intense heat which destroys cancer cells, often within 10 minutes. Microwave ablation is faster than RFA and thus reduces the time patients must remain under general anesthesia.  Surgeons can also ablate multiple liver tumors simultaneously and ablate larger tumors than with RFA.

• Cryosurgery: A treatment that uses an instrument to freeze and destroy abnormal tissue, such as carcinoma in situ. This type of treatment is also called cryotherapy. The doctor may use ultrasound to guide the instrument.

• Percutaneous Ethanol Injection: Ultrasound is used to guide a thin needle into the liver tumor. Alcohol (ethanol) is injected directly into the tumor and kills cancer cells. The procedure may be performed once or twice a week. Usually local anesthesia is used, but if the patient have many tumors in the liver, general anesthesia may be needed.  The patient may have fever and pain after the injection.

 

 

Embolization

For those who can't have surgery or a liver transplant, embolization or chemoembolization may be an option. The doctor inserts a tiny catheter into an artery in your leg and moves the catheter into the hepatic artery. For embolization, the doctor injects tiny sponges or other particles into the catheter. The particles block the flow of blood through the artery. Depending on the type of particles used, the blockage may be temporary or permanent.

Without blood flow from the hepatic artery, the tumor dies. Although the hepatic artery is blocked, healthy liver tissue continues to receive blood from the hepatic portal vein.

For chemoembolization, the doctor injects an anticancer drug (chemotherapy) into the artery before injecting the tiny particles that block blood flow. Without blood flow, the drug stays in the liver longer.

The patient must be sedated for this procedure, but general anesthesia is not usually needed. The patient will probably stay in the hospital for 2 to 3 days after the treatment.

Embolization often causes abdominal pain, nausea, vomiting, and fever. Your doctor can give the patient medicine to help lessen these problems. Some patients may feel very tired for several weeks after the treatment.

 

Targeted Therapy

Patients with liver cancer who cannot have surgery or a liver transplant may receive a drug called targeted therapy. Sorafenib (Nexavar) tablets were the first targeted therapy approved for liver cancer.

Targeted therapy slows the growth of liver tumors. It also reduces their blood supply. The drug is taken by mouth.

Side effects include nausea, vomiting, mouth sores, and loss of appetite. Sometimes, a patient may have chest pain, bleeding problems, or blisters on the hands or feet. The drug can also cause high blood pressure. The health care team will check your blood pressure often during the first 6 weeks of treatment.

 

 

Radiation Therapy

Radiation therapy uses high-energy rays to kill cancer cells. It may be an option for a few patients who can't have surgery. Sometimes it's used with other approaches. Radiation therapy also may be used to help relieve pain from liver cancer that has spread to the bones.

 

Doctors use two types of radiation therapy to treat liver cancer:

External radiation therapy: The radiation comes from a large machine. The machine aims beams of radiation at the chest and abdomen.

 

Internal radiation therapy: The radiation comes from tiny radioactive spheres. A doctor uses a catheter to inject the tiny spheres into your hepatic artery. The spheres destroy the blood supply to the liver tumor.The side effects from radiation therapy include nausea, vomiting, or diarrhea. Your health care team can suggest ways to treat or control the side effects.

 

 

Chemotherapy

Chemotherapy, the use of drugs to kill cancer cells, is sometimes used to treat liver cancer. Drugs are usually given by vein (intravenous). The drugs enter the bloodstream and travel throughout your body.

Chemotherapy may be given in an outpatient part of the hospital, at the doctor's office, or at home. Rarely, the patient may need to stay in the hospital.

 

The side effects of chemotherapy depend mainly on which drugs are given and how much. Common side effects include nausea and vomiting, loss of appetite, headache, fever and chills, and weakness.

Some drugs lower the levels of healthy blood cells, and the patient're more likely to get infections, bruise or bleed easily, and feel very weak and tired. Your health care team will check for low levels of blood cells. Some side effects may be relieved with medicine.

 

Supportive Care

Liver cancer and its treatment can lead to other health problems. The patient can have supportive care before, during, and after cancer treatment.

Supportive care is treatment to control pain and other symptoms, to relieve the side effects of therapy, and to help the patient cope with the feelings that a diagnosis of cancer can bring. The patient may receive supportive care to prevent or control these problems and to improve your comfort and quality of life during treatment.

 

Pain Control

 

Liver cancer and its treatment may lead to pain. Your doctor or a specialist in pain control can suggest several ways to relieve or reduce pain:

 

• Pain medicine: Medicines often can relieve pain. (These medicines may make patients drowsy and constipated, but resting and taking laxatives can help.)

• Radiation therapy: Radiation therapy can help relieve pain by shrinking the cancer.

• Nerve block: The doctor may inject alcohol into the area around certain nerves in the abdomen to block the pain.

 

The health care team may suggest other ways to relieve or reduce pain. For example, massage, acupuncture, or acupressure may be used along with other approaches. Also, the patient may learn to relieve pain through relaxation techniques such as listening to slow music or breathing slowly and comfortably.

 

Nutrition

Nutrition is important before, during, and after cancer treatment. Patients need sufficient amount of calories, protein, vitamins, and minerals. This may be a challenge because the patient may feel uncomfortable or tired, and may not feel like eating. The patient also may have side effects of treatment such as poor appetite, nausea, vomiting, or diarrhea. A doctor, a registered dietitian, or another health care provider can advise the patient about ways to have a healthy diet. 

 

Careful planning and checkups are important. Liver cancer and its treatment may make it hard for the patient to digest food and maintain your weight. The treatment team will monitor the patient for weight loss, weakness, and lack of energy.

 

Follow-up Care

The patient will need regular checkups (such as every 3 months) after treatment for liver cancer because the cancer may come back (a recurrence). Checkups help ensure that any changes in health are noted and treated if required. Checkups may include a physical exam, blood tests, ultrasound, CT scans, or other tests.

 

For patients who have had a liver transplant, the doctor will test how well the new liver is working. The doctor also will watch the patient closely to make sure the new liver isn't being rejected. Patients who have had a liver transplant may want to discuss with the doctor the type and schedule of follow-up tests that will be needed.