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Hepatocellular Carcinoma: Causes, Symptoms, Diagnosis, Treatment, and Prevention

A type of liver cancer, hepatocellular carcinoma (HCC) starts in the liver cells. Unlike other cancers, it does not spread from other organs to the liver.

Causes of HCC

The exact cause of HCC is not known, but there are some factors that can increase the risk of developing it. These include:

• Chronic infection with hepatitis B or C viruses, which can damage the liver and cause inflammation and scarring (cirrhosis).

• Cirrhosis from other causes, such as alcohol abuse, nonalcoholic fatty liver disease, autoimmune hepatitis, or inherited disorders.

• Exposure to aflatoxins, which are toxins produced by certain molds that can contaminate some foods, especially peanuts, corn, and grains.

• Diabetes and obesity, which can cause insulin resistance and fatty liver disease.

• Anabolic steroids, which are synthetic hormones that can affect the liver function and increase the risk of tumors.

• Iron overload, which is a condition where too much iron is stored in the liver and other organs.

Symptoms of HCC

HCC may not cause any symptoms in the early stages, but as the tumor grows, it may cause:

• Pain or discomfort in the upper right abdomen.

• Swelling or fluid buildup in the abdomen (ascites).

• Loss of appetite, weight loss, or feeling full after eating small amounts.

• Nausea, vomiting, or indigestion.

• Jaundice, which is yellowing of the skin and eyes due to high levels of bilirubin in the blood.

• Itching, which is caused by bile salts accumulating in the skin.

• Weakness, fatigue, or fever.

• Bleeding or bruising easily, which is due to low levels of clotting factors in the blood.

• Enlarged veins on the abdomen, chest, or neck, which are caused by increased pressure in the portal vein that carries blood from the digestive organs to the liver.

Diagnosis of HCC

To diagnose HCC, the doctor may perform:

• A physical exam, to check for signs of liver disease, such as jaundice, ascites, or enlarged liver or spleen.

• Blood tests, to measure the levels of liver enzymes, bilirubin, albumin, and alpha-fetoprotein (AFP), which is a protein that may be elevated in some people with HCC.

• Imaging tests, such as ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI), or positron emission tomography (PET) scan, to get detailed pictures of the liver and the tumor.

• Biopsy, which is a procedure where a small sample of the liver tissue is taken and examined under a microscope to confirm the diagnosis and determine the type and grade of the cancer.

Treatment of HCC

Based on the size, location, and number of tumors, the stage, liver function, and overall health of the patient, HCC treatment varies. The main goals of treatment are to remove or destroy the tumor, prevent or delay its spread, and relieve its symptoms. Possible treatments include:

• An open or laparoscopic procedure may be used to remove the tumor and some surrounding healthy tissue. Surgery may be curative if the tumor is small and confined to the liver, and if the liver functions well. Many people with HCC do not qualify for surgery, however, because the tumors may be too large, too many, or too close to vital structures.

• As the name implies, liver transplantation involves replacing a diseased liver with a healthy one. In some cases, liver transplantation is curative, but it is limited by donor availability and infection and rejection risks. In order to be eligible for liver transplantation, a person must meet certain criteria, such as having a small tumor less than 5 cm or three smaller tumors less than 3 cm each, and not having cancer spread outside the liver.

• In ablation, the tumor cells are destroyed with heat, cold, or chemicals. It can be done by insertion of a needle or probe through the skin or by placing electrodes on the liver's surface. An ablation may be used as an alternative to surgery or transplantation for small tumors that cannot be removed by surgery.

• By injecting a substance into the artery that feeds the tumor, or by placing small beads or coils into the artery, embolization blocks the blood supply to the tumor. In order to deliver drugs or radioactive particles directly to the tumor, embolization may be combined with chemotherapy (chemoembolization) or radiation (radioembolization). A tumor may be embolized if it cannot be treated by surgery or ablation, or if it needs to be shrunk before surgery or transplantation.

• High-energy rays or particles are used in radiation therapy to kill tumor cells. Radiation therapy can be delivered externally (external beam radiation) or internally (brachytherapy). It is used to treat tumors that cannot be treated by surgery, ablation, or embolization, or to relieve pain or bleeding symptoms.

• The use of drugs to destroy tumor cells is known as chemotherapy. Chemotherapy is usually administered by mouth, injection, or infusion. It can be used to treat tumors that have spread outside the liver, or to relieve symptoms. However, chemotherapy is not very effective when treating HCC, and it can cause serious problems.

• In targeted therapy, specific molecules or pathways that affect tumor growth and spread are targeted with drugs. The treatment can be administered orally or by infusion. When other treatments are ineffective or tolerated, targeted therapy may be used for advanced or recurrent HCC. One of the most commonly used targeted therapies for HCC is sorafenib, which blocks the signals that stimulate tumor blood vessel growth and cell division. There are several other targeted therapies being studied or approved for HCC, including lenvatinib, regorafenib, cabozantinib, and ramucirumab.

• The use of drugs that stimulate the immune system to recognize and attack cancer cells is known as immunotherapy. HCC can be treated with immunotherapy by infusion. If other treatments fail to work or are tolerated, immunotherapy may be used. Nivolumab is the most commonly used immunotherapy for HCC because it blocks a protein that prevents immune cells from attacking the tumors. Pembrolizumab, atezolizumab, and durvalumab are other immunotherapies being studied or approved for HCC.

Prevention of HCC

The best way to prevent HCC is to reduce the risk factors that can cause liver damage and cirrhosis. Some of the preventive measures include:

• Getting vaccinated against hepatitis B virus, which can prevent infection and chronic liver disease.

• Getting tested and treated for hepatitis B or C virus, which can prevent or slow down the progression of liver disease and reduce the risk of HCC.

• Avoiding or limiting alcohol consumption, which can cause liver inflammation and cirrhosis.

• Maintaining a healthy weight and diet, which can prevent or reverse fatty liver disease and diabetes.

• Avoiding exposure to aflatoxins, which can be found in some foods that are contaminated by mold.

• Avoiding or limiting the use of anabolic steroids, which can affect the liver function and increase the risk of tumors.

• Avoiding or limiting exposure to other chemicals or toxins that can harm the liver, such as arsenic, vinyl chloride, or thorium dioxide.

• Getting regular screening for HCC, especially if you have cirrhosis or chronic hepatitis B or C infection. Screening may involve blood tests and imaging tests to detect any abnormal growths in the liver. Early detection and treatment of HCC can improve the chances of survival and cure.