Screening for Hepatocellular Carcinoma
The most appropriate screening test for a 60-year-old male at risk for HCC is abdominal ultrasound performed every 6 months, which can be combined with AFP measurement to increase detection rates, though ultrasound alone is superior to AFP alone.
Recommended Screening Approach
Six-monthly abdominal ultrasound is the primary screening modality for HCC surveillance in high-risk populations, with sensitivity of 72% (95% CI 63-79%) and specificity of 94% (95% CI 91-96%) 1. This approach should be performed by an operator skilled in assessing patients with chronic liver disease using appropriate dedicated equipment 1.
Combining Ultrasound with AFP
The combination of ultrasound and AFP (at 20 ng/mL cut-off) achieves the highest sensitivity at 96% (95% CI 88-98%) with specificity of 85% (95% CI 73-93%), meaning less than 5% of HCC cases would be missed 2.
Adding AFP to ultrasound increases early-stage HCC detection from 45% to 63% in high-risk populations 3.
In a large Chinese randomized trial of 18,816 patients, screening with AFP and ultrasonography every 6 months resulted in a 37% reduction in HCC mortality 1.
Why Not the Other Options?
Liver Function Tests (Option A)
- Liver function tests have no role in HCC screening as they do not detect hepatocellular carcinoma and only assess hepatic synthetic function 1.
AFP Alone (Option B)
AFP should never be used as the only screening test due to inadequate sensitivity and poor positive predictive value 1, 3.
At the commonly used 20 ng/mL cut-off, AFP has only 60% sensitivity and 84% specificity, meaning 40% of HCC cases would be missed 2.
In populations with 5% HCC prevalence (typical of liver clinics), AFP at 20 ng/mL has a positive predictive value of only 41.5% 1, 3.
Up to 35-40% of HCC cases have normal AFP levels, even with large tumors 3.
AFP can be falsely elevated in active hepatitis, regenerating cirrhotic nodules, cholangiocarcinoma, colon cancer metastases, and other conditions 3.
Triphasic CT Scan (Option D)
CT is not appropriate for screening but rather serves as a confirmatory diagnostic test after a suspicious lesion is detected on ultrasound 1, 4.
Using CT as a screening test would result in significant radiation exposure when performed every 6-12 months over many years 1.
CT has an unacceptably high false-positive rate when used for screening rather than diagnosis 1.
The performance characteristics of CT have been developed for diagnostic/staging studies, not surveillance 1.
Clinical Algorithm for This Patient
Perform abdominal ultrasound every 6 months with an experienced operator 1.
Measure serum AFP concurrently to maximize detection rates 1.
If ultrasound detects a liver nodule or AFP is rising, proceed to diagnostic imaging with triphasic CT or MRI 1, 4.
For lesions ≥2 cm with typical arterial enhancement and portal venous washout on CT/MRI, HCC can be diagnosed without biopsy if AFP >200 ng/mL 3, 4.
Important Caveats
Ultrasound is highly operator-dependent, so quality depends on the skill and training of the ultrasonographer 1.
Scanning is difficult in obese patients, which may reduce sensitivity 1.
Despite correct surveillance, there is no definitive proof that early detection improves long-term survival, though this may reflect treatment limitations rather than diagnostic inadequacy 1.
Patients should be informed of the implications of early diagnosis and the lack of proven survival benefit before entering surveillance programs 1.