Doctors often monitor tumor markers in the blood to help diagnose and treat liver cancer. Alpha-fetoprotein (AFP) is the most common tumor marker that doctors monitor.

Liver cancer is one of the leading causes of death in the United States. A combination of genetics and environmental factors such as hepatitis infection and high alcohol consumption play a role in its development.

Tumor markers, also called biomarkers, are substances produced by cancer cells that can be detected in your blood. Doctors use tumor markers to:

  • help diagnose liver cancer
  • monitor how well your treatment is working
  • estimate your outlook

Alpha-fetoprotein (AFP) is the most common tumor marker doctors evaluate, but many other tumor markers are under investigation.

Liver cancer fast facts

  • The American Cancer Society estimates 41,210 people in the United States will receive a diagnosis of liver cancer in 2023.
  • Liver cancer rates have tripled since the 1980s.
  • Long-term alcohol abuse and chronic infectious hepatitis are the leading risk factors for liver cancer.
  • Asian Americans and Pacific Islanders have the highest rates of liver cancer in the United States.
  • The most common type of liver cancer, hepatocellular carcinoma (HCC), is much more common in men than women. The fibrolamellar subtype occurs more in women.
  • Although we typically avoid using “men” and “women” in favor of more inclusive terms, specificity is key when reporting on clinical findings, and the survey referenced didn’t report data on people who were transgender, nonbinary, gender nonconforming, genderqueer, agender, or genderless.
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AFP is the most common tumor marker doctors monitor for liver cancer. Researchers are still investigating the potential benefits of monitoring other tumor markers.


AFP is a molecule usually produced by the liver and yolk sac of unborn babies. Its main function is to help transfer molecules from the pregnant person to the fetus such as copper, fatty acids, and bilirubin.

AFP is normally found in small amounts in the blood of adults. High amounts of AFP suggest HCC, the most common type of liver cancer.

AFP levels can also be elevated in people who are pregnant and people with other liver diseases, such as:

  • liver cirrhosis
  • liver necrosis
  • chronic hepatitis

AFP variants

Researchers have identified three variants of AFP called AFP-L1, AFP-L2, and AFP-L3.

AFP-L3 is specific to liver cancer. The ratio of AFP-L3 to total AFP can potentially help doctors differentiate liver cancer from other types of liver disease.

An AFP-L3 to total AFP ratio more than 10% is suggestive of HCC.

Abnormal prothrombin (APT)

Abnormal prothrombin (APT) can be found in the blood of people with HCC or vitamin K deficiency. It’s been used as a tumor marker for diagnosing liver cancer in Japan, Europe, and the United States for many years.

APT goes by other names, such as:

  • protein induced by vitamin K antagonist-II
  • des-γ-carboxyprothrombin
  • acarboxy prothrombin

GOLGI 73 (also known as GOLPH 2 or GP 73)

GP 73 is a protein expressed in many tissues in humans but rarely in liver cells. Injury to liver cells can cause GP 73 levels to rise in your blood.

GP 73 isn’t a specific biomarker for liver cancer but might be a potentially useful biomarker for identifying cancer in general. Elevated levels have been noted in other cancers, such as:

Phosphatidylinositol proteoglycan (GPC3)

Many studies in recent years have found that GPC3 is highly expressed in liver cancer tissue but not in normal adult liver tissue. GPC3 may be a useful supplementary biomarker for detecting HCC.

Heat shock protein

Heat shock protein is significantly expressed in early liver cancer cells. Higher levels of heat shock protein have been associated with a poorer outlook for people with HCC.

Dickkopf-1 (DKK1)

The exact function of DKK1 isn’t clear, but levels in the blood are often elevated in people with various cancers, rheumatoid arthritis, and lupus.

Osteopontin (OPN)

OPN is secreted by cells in your bile duct. Overexpression has been linked to:

Research suggests the detection rate of HCC increases when OPN testing is combined with AFP and other biomarkers.

Tumor marker testing can potentially help doctors detect liver cancer before symptoms develop.

It’s generally accepted that people with AFP levels more than 400 nanograms per milliliter (ng/mL) can receive a diagnosis of liver cancer. But the use of AFP testing is still controversial since it provides high false-negative rates, meaning it suggests you don’t have liver cancer when you do.

Research suggests that using a cutoff value of 400 ng/mL for AFP correctly identifies people who don’t have liver cancer in 95–100% of cases but only correctly identifies liver cancer in 20–45% of cases.

The American Association of Liver Diseases recommends that people with cirrhosis receive ultrasound with or without AFP testing every 6 months.

Combining AFP testing with testing for other tumor markers may improve detection. AFP testing combined with an AFP-L3 cutoff of 15% may correctly identify as many as 75% of cases.

Doctors can use tumor markers such as AFP to determine whether you’re responding to treatment. A notable increase in AFP can indicate that your cancer has spread to distant parts of your body.

In a 2022 study, researchers found that elevated AFP or APT levels were highly predictive of relapse in people with a complete response to HCC treatment.

Some tumor markers can help doctors predict your outlook. For example, a concentration of AFP greater than 10 ng/mL has been linked to poorer survival times.

Higher levels of heat shock protein and GP73 levels may also be predictive of a poorer outlook.

Doctors use tumor markers to help detect liver cancer, monitor your response to treatment, and predict your outlook. The most common tumor marker that doctors monitor is called AFP.

Researchers are continuing to examine the role of other tumor markers in monitoring liver cancer. Combining some other markers such as AFP-L3 with AFP may help improve the accuracy of diagnosis.