What is the recommended screening protocol for liver cancer in high-risk individuals?

Recommended Screening Protocol for Liver Cancer in High-Risk Individuals

Ultrasound examination of the liver every 6 months is the recommended screening protocol for hepatocellular carcinoma (HCC) in high-risk individuals, with the optional addition of alpha-fetoprotein (AFP) testing to increase sensitivity. 1

High-Risk Populations Requiring Screening

Cirrhotic Patients

• All patients with cirrhosis should be offered surveillance for HCC unless they have a relatively high risk of death from non-HCC causes or are ineligible for curative treatment (e.g., Child-Pugh class C cirrhosis patients ineligible for liver transplantation) 1
• This includes cirrhosis from all etiologies, though risk varies by cause 1

Non-Cirrhotic Patients with Viral Hepatitis

• Chronic hepatitis B carriers with specific risk factors:
  • Asian men >40 years 1
  • Asian women >50 years 1
  • African/North American blacks 1
  • Family history of HCC 1
• Non-cirrhotic HBV patients at intermediate or high risk according to PAGE-B classes for Caucasians 1
• Non-cirrhotic patients with chronic hepatitis C and advanced liver fibrosis (F3) 1, 2

Advanced Fibrosis

• Patients with chronic liver disease and advanced fibrosis without cirrhosis have a higher risk of HCC than the general population, though evidence for routine surveillance in this group is insufficient 1, 2
• Non-alcoholic steatohepatitis (NASH) with advanced fibrosis should be considered for screening 1

Recommended Screening Protocol

Primary Screening Method

• Ultrasound examination of the liver every 6 months 1
• The combined use of ultrasound with AFP increases sensitivity while decreasing specificity and is a reasonable option 1

Alternative Imaging When Ultrasound is Inadequate

• Dynamic contrast-enhanced CT or MRI may be utilized when liver ultrasound cannot be performed adequately (e.g., in patients with obesity, intestinal gas, or chest wall deformity) 1

Biomarkers

• AFP is the most widely used biomarker, though it has limited sensitivity for early-stage HCC 1
• In some Asian countries, particularly Japan, additional biomarkers such as des-gamma-carboxy prothrombin (DCP) and AFP-L3 are recommended alongside AFP 1
• The GALAD score (incorporating gender, age, AFP, AFP-L3, and DCP) is being evaluated in clinical trials as a potential alternative screening approach 3

Follow-up of Abnormal Findings

For Nodules <1 cm

• Repeat ultrasound at 3-4 months 1

For Nodules ≥1 cm

• First-line imaging with multiphasic contrast-enhanced CT or MRI with extracellular contrast agent or hepatocyte-specific contrast agent 1
• If first-line imaging is inconclusive, second-line imaging or biopsy should be considered 1

Special Considerations

Surveillance Intervals

• Standard interval: Every 6 months for all high-risk groups 1
• Some Asian guidelines (particularly Japanese) recommend more frequent surveillance (every 3-4 months) for extremely high-risk groups such as patients with HBV/HCV-related cirrhosis 1

Diagnostic Criteria

• Non-invasive diagnosis of HCC should be based on the LI-RADS CT/MR v2018 or the LI-RADS CEUS v2017 criteria 1
• Typical hallmarks include arterial phase hyperenhancement with washout appearance in portal venous or delayed phases 1

Implementation Challenges

• Patient compliance is a major challenge in implementing effective screening strategies 1
• Physician adherence to guidelines and resource availability also affect screening effectiveness 1
• Educational programs for practitioners and patients are essential to improve surveillance compliance 1

Emerging Approaches

• Blood-based biomarker panels are being investigated to improve both adherence and sensitivity of screening 3
• Abbreviated MRI protocols are being evaluated as potential screening tools with higher sensitivity than ultrasound 1, 3