Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. One of its challenges is that early HCC may cause few or no noticeable symptoms. For people at increased risk, regular surveillance can therefore play an important role in identifying suspicious changes before symptoms develop.

But not everyone has the same risk of HCC, and not everyone needs the same surveillance strategy. Understanding your underlying liver condition and individual risk factors is the first step in deciding what type of monitoring may be appropriate.

Who Is at Increased Risk for HCC?

HCC most often develops in people with underlying liver disease. Important risk factors discussed in the MoleculeDx scientific program include cirrhosis, chronic hepatitis B or C, and steatohepatitis or other chronic liver conditions.

Cirrhosis is particularly important because it can result from several different causes of chronic liver injury. Chronic hepatitis B can also increase HCC risk, including in some patients who have not developed cirrhosis.

Other conditions—such as metabolic liver disease, alcohol-associated liver disease, diabetes, and family history—may also contribute to an individual’s overall risk.

Having a risk factor does not mean that a person will develop liver cancer. It means that the individual’s risk should be considered in deciding whether ongoing HCC surveillance is appropriate.

Why Is Regular HCC Surveillance Important?

Early HCC can be difficult to recognize from symptoms alone. The draft correctly notes that early symptoms may not be easily recognized. 

Surveillance is therefore designed to look for signs of HCC before symptoms become the reason the cancer is discovered.

For many patients at increased risk, clinical surveillance is performed at regular intervals. The appropriate schedule depends on the patient’s underlying liver disease, individual risk, and healthcare provider’s recommendations.

Surveillance is not a one-time test. It is an ongoing process.

What Tests Are Used for HCC Surveillance?

Liver imaging plays an important role in HCC surveillance. Ultrasound is widely used because it is noninvasive and readily available. Blood testing for alpha-fetoprotein (AFP) may also provide useful information.

However, neither approach provides a complete answer in every patient.

Ultrasound performance can be affected by patient and liver characteristics, while some people with HCC have AFP levels within the normal range.

These limitations have encouraged research into additional blood-based approaches that examine molecular signals associated with cancer.

What If AFP Is Normal?

A normal AFP result does not establish that liver cancer is absent.

AFP is a protein biomarker. Some HCC tumors produce enough AFP to increase its concentration in blood, while others do not.

For someone who remains at increased risk of HCC, surveillance should therefore not end simply because AFP is normal.

This is one reason researchers are studying molecular markers that provide information about cancer biology that is different from AFP.

Looking for Cancer-Associated Molecular Signals in Blood:

One area of research involves fusion transcripts.

Cancer cells can undergo chromosomal rearrangements that join genetic material from different genes. These rearrangements can create fusion genes. When a fusion gene is expressed, it can produce an abnormal RNA molecule called a fusion transcript.

Research underlying MoleculeDx technology has demonstrated that selected fusion transcripts can be detected as circulating cell-free RNA in serum from patients with HCC.

Because different tumors can contain different molecular alterations, relying on one fusion transcript alone has limitations. The MoleculeDx research program therefore evaluates multiple cancer-associated fusion-transcript signals together.

Where Does the Liver Cancer Fusion Predictor Fit?

The MoleculeDx Liver Cancer Fusion Predictor uses Fusion-detect™ technology to analyze multiple cancer-associated fusion-transcript signals in blood.

This provides a type of molecular information that is different from conventional protein biomarkers such as AFP.

Published research from the MoleculeDx scientific program has evaluated multi-marker fusion-transcript approaches in HCC and non-HCC study populations, including computational models that combine multiple measured molecular features. 

These research findings provide the scientific foundation for continued development of blood-based molecular approaches to HCC screening.

What Does an HCC Screening Result Mean?

Screening and diagnosis are not the same thing.

A blood-based molecular result can provide additional information about cancer-associated signals, but it should be interpreted together with the patient’s medical history, underlying liver disease, imaging, and other clinical findings.

A positive molecular result does not by itself establish a diagnosis of HCC. Likewise, a negative result does not mean that a person at increased risk should discontinue appropriate surveillance. 

When findings raise concern for HCC, healthcare professionals may recommend additional evaluation, including diagnostic imaging.

Should You Consider HCC Screening?

The most important question is not simply, “Should everyone have a liver cancer blood test?”

A better question is:

“Am I at increased risk of HCC, and what surveillance strategy is appropriate for me?”

If you have cirrhosis, chronic hepatitis B or C, or another significant liver condition, discuss your individual HCC risk with a qualified healthcare professional.

Together, you can consider:

• your underlying liver condition and other risk factors;
• the appropriate surveillance schedule;
• the role of liver imaging;
• whether AFP or other blood testing is appropriate; and
• whether additional molecular information may be useful in your particular situation.

Surveillance Starts With Understanding Your Risk:

HCC can develop without obvious early symptoms, which is why appropriate surveillance matters for people at increased risk.

Imaging and established blood biomarkers remain important components of liver cancer surveillance, while advances in molecular diagnostics are creating additional ways to examine cancer-associated signals in blood.

The MoleculeDx Liver Cancer Fusion Predictor represents one such molecular approach, using multiple fusion-transcript signals to provide information that is biologically different from AFP.

The first step is understanding your individual risk:

If you have chronic liver disease or other important HCC risk factors, talk with your healthcare provider about an appropriate liver cancer surveillance plan.