What are the recommended imaging guidelines for screening and diagnosing hepatocellular carcinoma (HCC) in high-risk patients, such as those with cirrhosis or chronic hepatitis B infection?

Imaging Guidelines for Hepatocellular Carcinoma

Surveillance/Screening Strategy

For high-risk patients with cirrhosis or chronic hepatitis B, perform abdominal ultrasound plus serum AFP measurement every 6 months as the primary surveillance approach. 1

Who Requires Surveillance

• Patients with cirrhosis of any etiology (chronic hepatitis B, chronic hepatitis C, or other causes) 1, 2
• Chronic hepatitis B patients without cirrhosis if they meet specific criteria: Asian men >40 years, Asian women >50 years, or those with family history of HCC 2, 3
• Chronic hepatitis C with advanced fibrosis (F3) even without cirrhosis 1, 2

Surveillance Modality and Interval

• Ultrasound combined with AFP every 6 months is the standard approach with level A1 evidence 1, 4
• This combination increases early-stage HCC detection from 45% to 63% compared to ultrasound alone 4
• A large randomized trial of 18,816 patients demonstrated 37% reduction in HCC mortality with this approach 4
• When ultrasound cannot be performed adequately (obesity, poor acoustic windows), dynamic contrast-enhanced CT or MRI can serve as alternative surveillance tools 1

Important Surveillance Caveats

• Ultrasound sensitivity is only 72% (95% CI 63-79%) and is highly operator-dependent, requiring skilled operators with appropriate equipment 4
• AFP alone should never be used as the sole screening test due to inadequate sensitivity—35-40% of HCC cases have normal AFP levels 4
• Liver function tests have no role in HCC screening 4

Diagnostic Algorithm When Nodule Detected

For Nodules ≥1 cm

Proceed immediately to first-line diagnostic imaging with multiphasic contrast-enhanced CT or multiphasic contrast-enhanced MRI (using either extracellular contrast agents or hepatocyte-specific contrast agents like gadoxetic acid) 1

Diagnostic Criteria for "Definite HCC"

The radiological hallmarks that establish definite HCC diagnosis without biopsy are:

• Arterial phase hyperenhancement (APHE) PLUS washout appearance in portal venous, delayed, or hepatobiliary phases 1, 2
• These criteria apply only to lesions that do NOT show marked T2 hyperintensity or targetoid appearances 1
• For nodules ≥2 cm: One imaging study showing these hallmarks is sufficient for diagnosis 1
• For nodules 1-2 cm: Diagnostic criteria vary by guideline quality—most recent 2022 Korean guidelines accept one study in optimal settings, two studies in suboptimal settings 1

If First-Line Imaging is Inconclusive

• If principal imaging features absent but ancillary features present: Classify as "probable HCC" and proceed to second-line imaging 1
• Second-line options include: Repeat first-line study within 3 months, alternative first-line modality (CT if MRI done first, or vice versa), or contrast-enhanced ultrasound 1
• If still inconclusive: Consider biopsy or repeat imaging in 3-6 months depending on suspicion level 1

For Nodules <1 cm

• Repeat surveillance ultrasound within 3-4 months rather than proceeding to diagnostic imaging 1
• These small nodules have very low sensitivity on CT/MRI (10-43%) and most represent regenerative/dysplastic nodules 5

Contrast Agent Considerations

MRI Contrast Options

• Both extracellular agents (ECA) and hepatobiliary agents (HBA) are acceptable for first-line diagnostic imaging 1
• Hepatobiliary agents (gadoxetic acid/Gd-EOB-DTPA or gadobenate dimeglumine) provide additional hepatobiliary phase imaging showing hypointensity in HCC due to reduced OATP transporter function 1
• HBA-enhanced MRI has higher sensitivity for HCC detection than CT or ECA-MRI, with improved lesion-to-liver contrast 1
• No guideline recommends one MRI contrast type over another for diagnostic purposes 1

CT Protocol Requirements

• Single-phase CT or MRI cannot be used for diagnosis—imaging-based HCC diagnosis requires multiphasic dynamic contrast enhancement characteristics 1
• Washout appearance can be identified in portal venous or delayed phases 1

Emerging Alternatives (Not Yet Standard)

• Abbreviated MRI protocols show promise with 82% sensitivity versus 53% for ultrasound in surveillance settings, but safety of repeated contrast exposure and cost-effectiveness require further validation 1
• GALAD biomarker panel (gender, age, AFP, AFP-L3, DCP) shows promising sensitivity in cohort studies but is not yet incorporated into guidelines 6
• These alternatives should not replace standard surveillance until prospective outcome trials demonstrate clinical benefit 1, 6

Critical Pitfalls to Avoid

• Do not use triphasic CT for surveillance/screening—it is a diagnostic tool for characterizing detected lesions, not a screening modality due to radiation exposure and cost 4, 5
• Do not skip surveillance in successfully treated chronic hepatitis C—these patients remain at risk and require continued screening 1, 2
• Do not apply imaging diagnostic criteria to non-cirrhotic, non-hepatitis B patients—the positive predictive value of imaging hallmarks depends on high pre-test probability 1
• Ensure adequate ultrasound quality—suboptimal ultrasound is worse than no screening, as it provides false reassurance; consider alternative modalities in patients with obesity or MASLD where ultrasound performance degrades 6, 7