Liver Cancer Screening for High-Risk Individuals

Liver cancer screening or surveillance is essential for those in high-risk groups. This is particularly important for early detection of hepatocellular carcinoma (HCC), which accounts for the majority of primary liver cancer. Screening allows for HCC to be detected at an earlier stage, when treatment options are more effective and survival rates are higher. This article explores who is at risk for liver cancer and outlines screening methods to detect it early.

1. Patients with cirrhosis

Cirrhosis is a condition in which the liver suffers scarring, leading to severe liver damage. Metabolic dysfunction-associated liver disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH) is a leading cause of cirrhosis-related HCC. A recent study showed that the risk of developing HCC in patients with MASLD-related cirrhosis is approximately 0.7–2.6%.

Cirrhosis creates an environment ideal for cancer development, significantly increasing the risk of liver cancer. This liver disease is often a result of

• Alcohol-related liver damage: excessive use of alcohol over time damages liver cells
• Virus-related liver damage: chronic infections from hepatitis B or C viruses are major causes of cirrhosis
• Auto-immune liver disease: immune-mediated damage to the liver caused by diseases such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH)

2. Patients with hepatitis B without cirrhosis

Carriers of the hepatitis B virus (HBV) are at risk of liver cancer even if they do not have cirrhosis. These people tend to develop liver cancer at a younger age. Factors that increase the risk of liver cancer, specifically in individuals with an existing hepatitis B infection, are summarized below.

3. Patients with hepatitis C without cirrhosis

People with the hepatitis C virus (HCV) and advanced fibrosis are at risk of liver cancer. This is the case even if they do not have cirrhosis.

The American Association for the Study of Liver Diseases (AASLD) recommends surveillance for patients with advanced fibrosis (F3), even after they have achieved a sustained virological response (SVR) to treatment. This is because these patients are still at a higher risk of developing liver cancer. Conversely, HCC surveillance is not recommended for patients with early-stage fibrosis (F0–F2).

Related: Chronic Viral Hepatitis and Liver Cancer: From Infection to Cancer

4. Patients with genetic conditions

Patients with a family history of certain diseases are more prone to developing liver cancer. Some of these genetic disorders include:

• Porphyria: a rare disorder affecting heme production, causing an accumulation of toxic substances in the liver
• Hereditary hemochromatosis: excess iron absorption resulting in a toxic buildup of iron in the liver
• α1-antitrypsin deficiency: accumulation of α1-antitrypsin in the liver
• Wilson's disease: impaired copper excretion resulting in a toxic buildup of copper in the liver
• Glycogen storage disease: a disorder affecting the body’s ability to store or use glycogen, causing a toxic accumulation of glycogen in the liver
• Tyrosinemia: impaired ability to break down tyrosine

Individuals with such disorders should remain under regular surveillance, regardless of the severity of their condition. This is to ensure that any signs of cancer are detected early and treatment can be started promptly.

5. Patients with a history of liver cancer

People who have had liver cancer before are at risk of recurrence or relapse. Regular imaging and blood tests should be carried out to monitor for signs of recurrence. Major guidelines recommend imaging every 3 to 6 months for the first 2 years after treatment, followed by every 6 to 12 months after that. Discuss with your healthcare provider about a detailed survivorship care plan to determine the best approach for you.

While there are no universal standards for liver cancer screening, early detection methods remain crucial for high-risk groups.

One of the most common methods for liver cancer screening is abdominal ultrasound. This imaging technique typically focuses on the liver, with some cases also evaluating the spleen.

Computed tomography (CT) and magnetic resonance imaging (MRI) are not typically used as primary surveillance methods. Both tests are costly, and CT scans come with added risks of radiation exposure. These tests are highly sensitive for further evaluation of larger tumors. They can also help assess potential spread outside of the liver.

Combinations of ultrasound and alpha-fetoprotein (AFP) blood tests increase sensitivity in detecting liver cancer, particularly in its early stages. If AFP levels exceed 400 ng/mL and a lesion is visible from the ultrasound, it is highly likely to be liver cancer. Studies show that using contrast-enhanced ultrasound alongside AFP testing can improve early-stage liver cancer detection by more than 60% in some patients. However, AFP testing alone has poor sensitivity and can produce false positive results.

Current international guidelines recommend abdominal ultrasound with or without AFP blood tests every 6 months, rather than every 12 months. This offers better sensitivity for detecting liver cancer at an early stage.

If a lesion is found during liver cancer screening, the next steps depend on the size of the lesion.

Lesions smaller than 1 cm

Small lesions may be benign. However, doctors will monitor these lesions closely with follow-up ultrasounds every three months until the lesions disappear.

• If the lesion does not grow, the three-month surveillance will continue
• Doctors will order further evaluation if:
  • The lesion grows to 1 cm
  • Larger or new lesions of similar size appear
  • The AFP level increases

Lesions 1 cm or larger

Lesions that are 1 cm or larger need further evaluation with detailed imaging, such as CT or MRI. Using a contrast agent improves the visibility of the lesion.

Doctors may diagnose liver cancer based on imaging features. Imaging helps determine the size, growth and shape of the lesion to confirm if it is cancerous. When the imaging results are inconclusive, a biopsy may be carried out for further evaluation.

Early detection of liver cancer, when effective treatments are available, significantly improves survival rates. This can be achieved by taking proactive steps in monitoring liver health and undergoing regular screening.