Hepatocellular Carcinoma

Synonyms

2

Overview

Hepatocellular carcinoma (HCC) is a malignant tumor that arises from hepatocytes in the liver. Hepatocellular carcinoma is relatively rare in the United States but very common in the sub-Sahara African countries and in Southeast Asia. Most cases are seen in patients over the age of 50 years, but this tumor can also occur in younger individuals and even in children. Hepatocellular carcinoma is more common in males than females and is associated with hepatitis B, hepatitis C, chronic alcohol abuse and cirrhosis. Serum elevation of alpha-fetoprotein occurs in a large percentage of patients with hepatocellular carcinoma. Grossly, hepatocellular carcinoma may present as a single mass, as multiple nodules, or as diffuse liver involvement. Microscopically, there is a wide range of differentiation from tumor to tumor (well differentiated to poorly differentiated tumors).

Symptoms

Most people don't have signs and symptoms in the early stages of HCC. When signs and symptoms do appear, they may include:

  • Unexplained weight loss
  • Unexplained fevers
  • Loss of appetite
  • Abdominal pain (particularly in the right-upper quadrant)
  • Nausea and vomiting
  • General weakness and fatigue
  • Abdominal swelling
  • Yellow discoloration of your skin and the whites of your eyes (jaundice)
  • White, chalky stools

Causes

It's not clear what causes most cases of liver cancer. But in some cases, the cause is known. For instance, chronic infection with certain hepatitis viruses (Hepatitis B, C) can cause liver cancer.

Liver cancer occurs when liver cells develop changes (mutations) in their DNA — the material that provides instructions for every chemical process in your body. DNA mutations cause changes in these instructions. One result is that cells may begin to grow out of control and eventually form a tumor — a mass of cancerous cells.

Prevention

Factors that increase the risk of primary liver cancer include:

  • Chronic infection with HBV or HCV. Chronic infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV) increases your risk of liver cancer. You can reduce your risk of hepatitis B by receiving the hepatitis B vaccine, which provides more than 90 percent protection for both adults and children. There is no vaccine for hepatitis C exists, but you can reduce your risk of infection.
  • Cirrhosis. This progressive and irreversible condition causes scar tissue to form in your liver and increases your chances of developing liver cancer.
  • Excessive alcohol consumption. Consuming more than a moderate amount of alcohol daily over many years can lead to irreversible liver damage (cirrhosis) and increase your risk of liver cancer. Drink alcohol with moderation, if at all. 
  • Certain inherited liver diseases. Liver diseases that can increase the risk of liver cancer include hemochromatosis and Wilson's disease.
  • Diabetes. People with this blood sugar disorder have a greater risk of liver cancer than those who don't have diabetes.
  • Nonalcoholic fatty liver disease. An accumulation of fat in the liver increases the risk of liver cancer.
  • Exposure to aflatoxins. Aflatoxins are poisons produced by molds that grow on crops that are stored poorly. Crops such as corn and peanuts can become contaminated with aflatoxins, which can end up in foods made of these products. In the United States, safety regulations limit aflatoxin contamination. Aflatoxin contamination is more common in certain parts of Africa and Asia.
  • Overweight. Maintain a healthy weight. If your current weight is healthy, work to maintain it by choosing a healthy diet and exercising most days of the week. 

Diagnosis

The diagnosis is sometimes difficult to make and may be suspected in a patient with chronic liver disease who is found to have a high level of a protein, called Alpafoetoprotein (AFP), on a blood test. A CT scan or MRI scan is usually used to look for a mass in the liver. A tumour is not found, or lots of lumps are seen, one of which is larger than the others. One cannot be certain if the larger lump is a HCC, so then the scan is repeated after a suitable period of time.

If there are suspicions of an HCC in a patient who has not had chronic liver disease, and the image on the scan is not characteristic, a biopsy can be done, but has risks. For example, there is a risk of bleeding and also a risk of spreading the tumour along the line of the biopsy needle. This may impact on the treatment that can be offered.

The Blood test: alpha-foetoprotein (AFP) is a useful serum marker that is raised in approximately two thirds of patients with hepatocellular carcinoma and in much higher levels than in benign liver disease. The fibrolamellar type of HCC does not usually have raised levels of AFP.

The CA19-9 level (see colorectal carcinoma section) is raised in cholangiocarcinoma but the level rises in obstructive jaundice (i.e. when the biliary tree is obstructed) and as this occurs early in cholangiocarcinoma the test is usually of little use.

The definitive proof of the diagnosis is by biopsy (taking a piece of the tumour through a skin needle puncture access) and microscopic examination. Often, the abnormal liver function impacts on the blood’s clotting system and if the coagulation tests in the blood are sufficiently deranged, then the biopsy may be deemed risky and the diagnosis is then based on other criteria.

Tests and procedures used to diagnose liver cancer include:

  • Blood tests. Blood tests may reveal liver function abnormalities.
  • Imaging tests. Your doctor may recommend imaging tests, such as an ultrasound, computerized tomography (CT) scan and magnetic resonance imaging (MRI).
  • Removing a sample of liver tissue for testing. During a liver biopsy, a sample of tissue is removed from your liver and examined under a microscope. Your doctor may insert a thin needle through your skin and into your liver to obtain a tissue sample. Liver biopsy carries a risk of bleeding, bruising and infection.

Prognosis

Hepatocellular carcinomas quickly metastasize to regional lymph nodes and lung. The overall median survival of untreated liver cell carcinoma is about 4 months.

Treatment

Treatment options for Hepatocellular Carcinoma may include:

  • Surgery to remove a portion of the liver. In certain situations, your doctor may recommend partial hepatectomy to remove the liver cancer and a small portion of healthy tissue that surrounds it if your tumor is small and your liver function is good.

This option depends on the location of your cancer within the liver.

  • Liver transplant surgery. During liver transplant surgery, your diseased liver is removed and replaced with a healthy liver from a donor. Liver transplant surgery is only an option for a small percentage of people with early-stage liver cancer.
  • Freezing cancer cells. Cryoablation uses extreme cold to destroy cancer cells. During the procedure, your doctor places an instrument (cryoprobe) containing liquid nitrogen directly onto liver tumors. Ultrasound images are used to guide the cryoprobe and monitor the freezing of the cells.
  • Heating cancer cells. In a procedure called radiofrequency ablation, electric current is used to heat and destroy cancer cells. Using an ultrasound or CT scan as a guide, your surgeon inserts one or more thin needles into small incisions in your abdomen. When the needles reach the tumor, they're heated with an electric current, destroying the cancer cells.
  • Injecting alcohol into the tumor. During alcohol injection, pure alcohol is injected directly into tumors, either through the skin or during an operation. Alcohol causes the tumor cells to die.
  • Injecting chemotherapy drugs into the liver. Chemoembolization is a type of chemotherapy treatment that supplies strong anti-cancer drugs directly to the liver. During the procedure, chemotherapy drugs are injected into the hepatic artery — the artery from which liver cancers derive their blood supply — and then the artery is blocked. This serves to cut blood flow to the cancer cells and to deliver chemotherapy drugs to the cancer cells.
  • Radiation therapy. This treatment uses high-powered energy beams to destroy cancer cells and shrink tumors. During radiation therapy treatment, you lie on a table and a machine directs the energy beams at a precise point on your body. Radiation therapy for liver cancer may involve a technique called stereotactic radiosurgery that simultaneously focuses many beams of radiation at one point in the body.
  • Targeted drug therapy. Targeted drugs work by interfering with a tumor's ability to generate new blood vessels. They have been shown to slow or stop advanced hepatocellular carcinoma from progressing for a few months longer than with no treatment. More studies are needed to understand how targeted therapies, such as the drug sorafenib (Nexavar), may be used to control advanced liver cancer.