Liver Cancer (Hepatocellular Carcinoma)

Liver cancer is often the result of chronic liver disease.

The liver is the largest organ inside the body and is located under the right ribs and beneath the right lung. The liver has several functions. It secretes bile into the intestines to absorb fats, breaks down and stores nutrients, manufactures clotting factors needed to stop bleeding, and breaks down toxic agents, like alcohol and drugs. Once the toxic agents are broken down, they can be eliminated from the body through urine or stool. One of the causes of cirrhosis, the scarring of the liver, is alcoholism. A person cannot live without a liver, so liver shut down or liver failure is fatal.

Hepatitis is an inflammation of the liver, which can progress to scarring (fibrosis) or liver cancer. Hepatitis can be caused by toxic substances, infection, or autoimmune diseases. Common viruses that cause hepatitis are referred to as types A, B, C, D, and E. It's possible to prevent hepatitis with a vaccine available for types A, B, and E.

Liver cancer definition

Primary liver cancer is a condition or disease that happens when normal cells in the liver become abnormal in appearance and behavior. The cancer cells can then become destructive to adjacent normal tissues and can spread both to other areas of the liver and organs outside the liver. Liver cancer is also called hepatic cancer.

Malignant or cancerous cells that develop in the normal cells of the liver (hepatocytes) are called hepatocellular carcinoma. Cancer that arises in the ducts of the liver is called cholangiocarcinoma.

Metastatic cancer is cancer that has spread from the place where it first started (the primary site) to another place in the body (secondary site). Metastatic liver cancer is a rare condition that occurs when cancer originates in the liver (primary) and spreads to other organs (secondary) in the body.

Metastatic cancer in the liver is a condition in which cancer from other organs has spread through the bloodstream to the liver. Here the liver cells are not what have become cancerous. The liver has become the site to which cancer that started elsewhere has spread. Metastatic cancer has the same name and same type of cancer cells as original cancer. The most common cancers that spread to the liver are breast, colon, bladder, kidney, ovary, pancreas, stomach, uterus, and lungs.

Some people with metastatic tumors do not have symptoms. Their metastases are found by X-rays, CT scans, ultrasounds, or other tests. Enlargement of the liver or jaundice (yellowing of the skin) can indicate cancer has spread to the liver.

Incidence rates of hepatocellular cancer are rising in the United States due to the increasing prevalence of cirrhosis caused by chronic hepatitis C and steatohepatitis (nonalcoholic fatty liver disease).

Cirrhosis of the liver due to any cause is a risk factor for liver cancer. The risk factors for liver cancer in cirrhosis are being male, age 55 years or older, Asian or Hispanic ethnicity, family history in a first-degree relative, obesity, hepatitis B and C, alcohol use, and elevated iron content in the blood due to hemochromatosis.

Chronic hepatitis B infection even without cirrhosis is a risk factor for liver cancer.

What causes liver cancer?

Most people who get liver cancer get it in the setting of chronic liver disease (long-term liver damage called cirrhosis), which scars the liver and increases the risk for liver cancer. Conditions that cause cirrhosis are alcohol use/abuse, hepatitis B, and hepatitis C.

The causes of liver cancer may be linked to environmental, dietary, or lifestyle factors. For example, in November 2014, researchers at the University of California, San Diego School of Medicine, found that long-term exposure to triclosan, a common ingredient in soaps and detergents, causes liver fibrosis and cancer in laboratory mice. Although triclosan has not been proven to cause human liver cancer, it is currently under scrutiny by the FDA to determine whether it has negative health impacts.

Liver cancer causes no symptoms of its own. As the tumor grows, it may cause symptoms of pain in the right side of the abdomen or feeling overly full after eating a small amount. Some patients may have worsening symptoms of chronic liver disease or cirrhosis, which often precedes the development of cancer of the liver. For example, patients may complain of:

• unexplained weight loss, wasting (cachexia),
• decreased appetite,
• nausea or vomiting,
• a feeling of an enlarged liver (feeling a mass under the ribs on the right side),
• enlarged spleen (feeling a mass under the ribs on the left side),
• pain in the abdomen or near the right shoulder blade,
• increased swelling of the feet and belly,
• fluid build-up in the belly,
• itching,
• swollen legs, and
• yellowing of the eyes and skin (jaundice).

The best way to detect liver cancer is through surveillance ultrasound of the liver done by an oncologist every 6 months in a patient with a diagnosis of cirrhosis. As with most forms of cancer, it is best to treat liver cancer as soon as it is detected.

Once a suspicion of liver cancer arises, a physician will order one of the following to confirm a diagnosis:

1. Blood tests: alpha-fetoprotein (AFP), which may be elevated in 70% of patients with liver cancer. AFP levels could be normal in liver cancer. A rising level of AFP is suspicious for liver cancer. The AFP may be elevated with cirrhosis and chronic active hepatitis. Other labs tests include des-gamma-carboxy prothrombin, which can be elevated in most patients with liver cancer.
2. Imaging studies: Multiphasic helical CT scan and MRI with the contrast of the liver are the preferred imaging for detecting the location and extent of blood supply to cancer. If any imaging study is inconclusive, then an alternative imaging study or follow-up imaging study should be performed to help clarify the diagnosis. Lesions smaller than 1 cm are usually difficult to characterize.
3. A liver biopsy is performed to sample tissue from the lesion in the liver, which is analyzed by a pathologist to confirm the suspected diagnosis of liver cancer. A liver biopsy is not needed in every case, especially if the imaging study and lab markers are characteristic of liver cancer. Risks of liver biopsy are infection, bleeding, or seeding of the needle track with cancer. Seeding is when cancer cells get on the needle used for a biopsy and spread to other areas touched by the needle. Liver biopsy of suspected liver cancer carries the added risk of seeding the liver biopsy needle track in 1%-3% of cases. If a liver biopsy is inconclusive, then a repeat imaging study is recommended at 3- to 6-month intervals.

According to the American Cancer Society, "The stage of cancer is a description of how widespread it is. The stage of liver cancer is one of the most important factors in considering treatment options. A staging system is a standard way for the cancer care team, to sum up, information about how far cancer has spread. Doctors use staging systems to get an idea about a patient's prognosis (outlook) and to help determine the most appropriate treatment. There are several staging systems for liver cancer, and not all doctors use the same system."

Liver biopsy, as well as imaging studies, help in classifying liver cancer stages as per the American Joint Committee on Cancer (AJCC) TNM system, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Cancer of the Liver Italian Program (CLIP) system, or the Okuda system.

Benign liver tumors: This type of tumor can become large enough to cause problems but will not spread to other areas of the body. The treatment is usually surgery.

• Hemangioma: A hemangioma is a blood vessel tumor that only requires treatment if it bleeds.
• Hepatic adenoma: This is a type of benign liver tumor, which may cause abdominal pain or blood loss. Surgical removal is usually recommended.
• Focal nodular hyperplasia (FNH): This tumor is made up of several different types of cells (liver, bile duct, and connective tissue cells).

Liver angiosarcoma (or hepatic angiosarcoma) and hemangiosarcoma are rare. This is a cancer of the inner lining of the blood vessels. Since the symptoms of liver angiosarcoma are nonspecific, usually this type of liver cancer is not discovered until it is too late to be treated effectively.

• Hepatocellular carcinoma: This is the most common form of primary cancer. Primary liver cancer is cancer that began in the liver. It can occur as a single tumor or many small cancer nodules throughout the liver. Primary liver cancer will commonly spread to the lungs, the portal vein (kidney), and portal lymph nodes.
• Intrahepatic cholangiocarcinoma (bile duct cancer): As described by its name, this cancer starts where the bile duct connects to the liver. Between 10%-15% of the liver, cancers are of this type. This type of cancer commonly spreads (metastasizes) to the lymph nodes, lungs, and bone marrow.
• Hepatoblastoma: This is rare cancer found in children, usually under age 4. This cancer is treated, successfully in most cases, with surgery and chemotherapy.
• Secondary cancer: This is cancer that started elsewhere in the body and spread to the liver. This spread of cancer from a primary site to other parts of the body is called metastasis. Secondary liver cancer is more common in the United States than primary liver cancer. Secondary cancer will be treated by the techniques that have been successful for the primary type of cancer. For example, lung cancer that has spread to the liver will be treated using lung cancer protocols, which are the standards of medical care that have been effective for lung cancer.

Lymphoma, a cancer of the immune system including the lymph nodes, also commonly spreads to the liver. Pancreatic cancer may also spread to the liver.

The medical treatment chosen depends upon how much cancer has spread and the general health of the liver. For example, the extent of cirrhosis (scarring) of the liver can determine the treatment options for cancer. Similarly, the spread and extent of the spread of cancer beyond the liver tissue play an important part in the types of liver cancer treatment options that may be most effective.

• Surgery: Liver cancer can be treated sometimes with surgery to remove the part of the liver with cancer. Surgical options are reserved for the smaller sizes of cancer tumors. Complications from surgery may include bleeding (which can be severe), infection, pneumonia, or side effects of anesthesia.
• Liver transplant: The doctor replaces the cancerous liver with a healthy liver from another person. It is usually used in very small unresectable (inoperable or not able to be removed) liver tumors in patients with advanced cirrhosis. Liver transplantation surgery may have the same complications as noted above for surgery. Also, complications from medications related to a liver transplant may include possible rejection of the liver transplant, infection due to suppression of the immune system, high blood pressure, high cholesterol, diabetes, weakening of the kidneys and bones, and an increase in body hair.
• Ablation therapy: This is a procedure that can kill cancer cells in the liver without any surgery. The doctor can kill cancer cells using heat, laser, or injecting special alcohol or acid directly into cancer. This technique also may be used in palliative care when the cancer is unresectable.
• Embolization: Blocking the blood supply to cancer can be done using a procedure called embolization. This technique uses a catheter to inject particles or beads that can block blood vessels that feed cancer. Starving the cancer of the blood supply prevents the growth of cancer. When this technique uses chemotherapy and synthetic material, it is sometimes called chemoembolization, as it blocks off the blood supply and traps the chemotherapy agent in a tumor. This technique is usually used on patients with large liver cancer for palliation. Complications of embolization include fever, abdominal pain, nausea, and vomiting.
• Radiation therapy: Radiation uses high-energy rays directed to cancer to kill cancer cells. Normal liver cells are also very sensitive to radiation. Complications of radiation therapy include skin irritation near the treatment site, fatigue, nausea, and vomiting.
• Chemotherapy: Chemotherapy uses medicine that kills cancer cells. The medicine can be given by mouth or by injecting into a vein or artery feeding the liver. People can have a variety of side effects from chemotherapy, depending on the medications used and the patient's response. Complications of chemotherapy include fatigue, easy bruising, hair loss, nausea and vomiting, swollen legs, diarrhea, and mouth sores. These side effects are usually temporary.
• Targeted agent: Sorafenib (Nexavar) is an oral medication that can prolong survival (up to 3 months) in patients with advanced liver cancer. Side effects of sorafenib include fatigue, rash, high blood pressure, sores on the hands and feet, and loss of appetite.
• Clinical trial: A clinical trial is a way to receive specific treatments in a carefully controlled way to determine whether a new therapy approach is safe, effective, and better than existing therapies. A new treatment may be a drug, a device, a different way to do a surgery, a combination of two or more drugs, methods of treatment, or even diet. The government maintains a website at ClinicalTrials.gov where more information on trials related to liver cancer can be found. The research from clinical trials, including the statistics supporting the effectiveness of the intervention being tested, is important in the introduction of new treatment methods and ways to change the standard of medical care for all types of liver cancer.

What is the follow-up after treatment for liver cancer? 

Patients are advised to follow up with the doctor for lab tests and office visits. Patients with chronic liver disease should avoid alcohol and any drugs that can harm the liver. Patients with liver transplants will need to take anti-rejection drugs for the rest of their life to prevent their bodies from rejecting the new liver.

The prognosis for liver cancer depends on multiple factors such as the size of the liver cancer, the number of lesions, the presence of spread beyond the liver, the health of the surrounding liver tissue, and the general health of the patient. Life expectancy depends on many factors that impact whether cancer is curable.

The American Cancer Society states the overall 5-year survival rate for all stages of liver cancer is 22%. One of the reasons for this low survival rate is that many people with liver cancer also have other underlying medical conditions such as cirrhosis. However, the 5-year survival rate can vary depending on how much the liver cancer has spread.

If the liver cancer is localized (confined to the liver), the 5-year survival rate is 37%. If the liver cancer is regional (has grown into nearby organs), the 5-year survival rate is 14%. Once the liver cancer is distant (spread to distant organs or tissues), the 5-year survival is just 4%.

The survival rate can also be affected by the available treatments. Liver cancers that can be surgically removed have an improved survival rate. When caught in the earliest stages, and the liver is transplanted, the 5-year survival rate can be as high as 70%.

Primary liver cancer deaths are usually from liver failure, bleeding, or advanced cancer.

Is liver cancer curable?

Liver cancer is difficult to cure, as it is most often not caught in the early stage. When successfully treated, Liver cancer may never go away completely, so follow-up is very important. Blood tests and imaging tests may be part of a patient's survivorship plan. Statistics for liver cancer are difficult to apply to a specific patient, like the forms, stages, and responses to treatment vary per individual. The statistics for deaths due to liver cancer in 2023 are estimated at 19,120 men and 10,720 women.

Prevention of cirrhosis, which is the underlying cause of liver cancer, will help in preventing the development of liver cancer.

Routine surveillance for liver cancer by performing an ultrasound of the liver every 6 months in patients with a cirrhotic liver will detect early liver cancer.