Hepatocellular carcinoma is the most common liver cancer and the ninth leading cause of cancer deaths1.
The risk associated with chronic hepatitis B virus (HBV) infection is declining with HCV clearance in patients achieving sustained viral response with antiviral therapy.2
HCC is frequently diagnosed through surveillance, eg by abdominal ultrasound or elevated serum a-fetoprotein, in at-risk populations. The sensitivity of a biopsy is 70% and serial contrast-enhanced imaging is recommended in these patients.
Causes
Hepatocellular carcinoma occurs most often in people with chronic liver disease such as cirrhosis caused by hepatitis B or C virus infection. It is also more common in people who drink a lot of alcohol or have too much fat in the liver. There is a small risk that HCC will spread (metastasize) to other parts of the body, such as the bones or the lungs.
Liver cancer is the sixth most common cancer and the fourth leading cause of cancer-related death worldwide. It is most common in Asia, but has been increasing in incidence and mortality in the United States, Europe and elsewhere. The most common cause of HCC is hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, although non-alcoholic steatohepatitis (NASH), associated with metabolic syndrome and diabetes mellitus is growing as a major aetiology in the West.
HCC is the most common tumor of the liver, with a global incidence exceeding 1 million cases per year1. It represents 90% of all primary liver cancers2. The tumour is usually located in the central part of the liver and may appear on routine imaging studies as a bright red or maroon colouration with unpaired portal tracts, pseudo-glandular pattern and diffuse fatty changes.
The cellular origin of HCC is debated and can be thought to derive from either putative liver stem cells, a transit amplifying population or mature hepatocytes. The tumours are characterized by proliferation and activation of classical cell-proliferative pathways, including the PI3K-AKT-mTOR, Wnt/-catenin and IGF-2 signalling cascades.
Diagnosis
Hepatocellular carcinoma (HCC) is cancer that starts in the liver. It most often occurs in people who have long-term problems with their liver, such as cirrhosis that develops from chronic hepatitis B or C infection. It also is common in people who drink too much alcohol or have too much fat stored in their livers.
In the early stages, HCC is slow-growing. It can be cured by surgery to remove the tumor and by a liver transplant. If it is more advanced, or if the cancer has spread outside the liver, there is no chance for a cure. The goal of treatment is to improve symptoms and extend life. Treatment may include drugs that kill cancer cells or block new blood vessels that tumors need to grow. Some of these drugs can be taken as pills, while others are injected into a vein or pumped into the liver through a tube called a catheter.
A doctor can diagnose hepatocellular carcinoma by doing a physical exam and asking about your health history. Your doctor will order blood tests to check for liver damage, such as increased levels of a protein that is released into the blood when cancer cells start growing. Other tests may include an ultrasound, CT scan, and MRI.
If you are diagnosed with hepatocellular carcinoma, your doctor will explain your treatment options. They may recommend surgery, radiation, chemotherapy, targeted therapy, or immunotherapy. Your doctor will discuss which option is best for you based on the size and location of your tumor, how well your liver functions, and whether it has spread.
Molecular imaging can detect HCC at an earlier stage than traditional clinical imaging methods. It is a technique that allows doctors to see molecular changes in the tissue, such as a mutation in a specific gene, at a certain point in the process of cell growth. Eventually, this technology may lead to a test that can identify HCC before it causes many symptoms.
You and your family can learn about hepatocellular carcinoma by talking with your doctor or joining a support group for patients and families of people who have liver disease. Support groups can help you feel less alone and find out what treatments and medications are available for your illness.
Treatment
The best treatments for hepatocellular carcinoma are surgery to remove the tumor and a liver transplant. These can cure the cancer in people with good liver function and a small tumor that has not spread. If these options are not available, there are other ways to ease symptoms and slow tumor growth, which can help patients live longer.
Doctors use blood tests to measure the amount of enzymes in the liver, which are a sign of how well or poorly the liver is working. If the enzymes are high, it can indicate a problem with how the liver is making proteins or how much fat is stored in the body.
There are several different treatment methods for HCC, including surgery, radiation, and chemotherapy drugs. Doctors also treat the disease by stopping or preventing complications. These include removing excess fluid from the abdomen (ascites), managing any other diseases that may cause hepatocellular carcinoma, such as cirrhosis, and lowering cholesterol and triglyceride levels.
Surgery to remove the tumor is usually the first choice for treating hepatocellular carcinoma. This can be done by removing a wedge of tissue, an entire lobe or part of the liver, and sometimes the surrounding liver tissue.
Another surgical treatment for hepatocellular carcinoma is a procedure called radiofrequency ablation. During this treatment, doctors use special needles that are inserted into the tumor. High-energy radio waves are then used to heat the needles and the tumor, which kills cancer cells. Doctors can also use microwave therapy or ethanol injection to destroy tumors.
Chemotherapy is a group of drugs that works to kill cancer cells and shrink tumors. Different groups of chemotherapy drugs work in different ways. Doctors can use a combination of these drugs to treat hepatocellular carcinoma.
A new type of treatment for hepatocellular carcinoma is targeted therapy. During this type of treatment, doctors give a drug that targets a specific protein or molecular pathway involved in the growth and spread of the cancer. This treatment is usually given along with other types of treatment, such as a drug that stops the formation of new blood vessels in the cancerous tissues.
Prevention
About 90 to 95 percent of hepatocellular carcinomas result from chronic infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV). In most cases, HBV or HCV causes hepatocellular injury, which leads to fibrosis and eventually to liver cancer. Hepatitis B and hepatitis C are the leading causes of liver cancer in many countries, including the United States. Several studies have shown that HBV or hepatitis C virus vaccination significantly reduces the risk of developing hepatocellular carcinoma. Furthermore, treatment of HBV and hepatitis C virus infections with long-term entecavir therapy results in the reversal of fibrosis and improvement in hepatocellular carcinoma markers in most patients.
Primary prevention of hepatocellular carcinoma can be achieved by avoiding exposure to known risk factors for the disease. This includes abstaining from alcohol and avoiding unsafe sex practices, such as unprotected sex, sharing needles for drug use and taking antibiotics without a prescription. Hepatitis viruses can also spread through contaminated blood transfusions, but this risk is now almost zero because all donated blood in the United States is tested for both hepatitis B and hepatitisC virus antibodies.
Other major risk factors include cirrhosis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, which contribute to 75 to 80% of hepatocellular carcinoma worldwide. Fortunately, these risks can be reduced by abstaining from smoking, drinking only moderate amounts of alcohol and losing weight.
It is important to remember that even though hepatocellular carcinoma is the sixth leading cause of cancer-related death in the world, it remains a highly curable disease. With the advent of new antiviral agents, it is now possible to eradicate HBV and hepatitis C infection in large numbers of individuals and prevent progression to hepatocellular carcinoma. However, hepatocellular carcinoma is still on the rise in Europe and Africa, although hepatocellular carcinoma rates continue to decline in traditionally endemic areas such as East Asia. This trend is projected to continue. Surveillance Epidemiology and End Results (SEER) data have shown that hepatocellular carcinoma is increasing in the United States as well, although at a much lower rate than in other regions of the world.