What are the diagnostic criteria for hepatocellular carcinoma (HCC)?

Diagnostic Criteria for Hepatocellular Carcinoma

In cirrhotic patients or those with chronic HBV infection, HCC diagnosis should be based on LI-RADS CT/MRI v2018 criteria showing arterial phase hyperenhancement with washout in portal venous or delayed phases for nodules ≥1 cm, without requiring biopsy. 1

Non-Invasive Diagnostic Approach

Imaging Criteria (LI-RADS System)

The LI-RADS classification should be preferred over older algorithms because it provides valuable refinements including LR-M and LR-TIV categories and estimates HCC probability in nodules not meeting LR-5 criteria. 1

For multiphasic CT or MRI, the following features establish diagnosis:

• Arterial phase hyperenhancement (non-rim pattern) 1
• Washout in portal venous or delayed phases (peripheral or non-peripheral pattern) 1
• Enhancing capsule 1
• Threshold growth 1
• Tumor size ≥1 cm 1

For contrast-enhanced ultrasound (CEUS), diagnostic criteria require:

• Non-rim arterial hyperenhancement 1
• Late-onset washout (>60 seconds) of mild intensity 1

Imaging Modality Selection

Multiphasic CT or dynamic contrast-enhanced MRI are equally recommended as first-line diagnostic tools, with no preference between them. 1 However, extracellular contrast agents should be favored over gadoxetic acid for non-invasive HCC diagnosis using MRI. 1

CT or MRI should be preferred over CEUS as the first-line examination because of higher sensitivity and ability to analyze the entire liver. 1 CEUS is appropriate as a second-line modality when first-line imaging is inconclusive. 1

Size-Based Diagnostic Algorithm

Nodules <1 cm

• Repeat surveillance ultrasound every 3-4 months for the first year, then every 6 months thereafter 1
• Most nodules <1 cm are not HCC and require close monitoring rather than immediate intervention 1

Nodules 1-2 cm

• Perform multiphasic CT or MRI as first-line imaging 1
• One positive imaging study showing typical hallmarks (arterial hyperenhancement with washout) is sufficient for diagnosis 1
• If imaging is inconclusive, obtain second-line imaging (alternative modality) or consider biopsy 1
• The Korean guidelines allow diagnosis with elevated AFP (≥200 ng/mL) combined with typical imaging features 1, 2

Nodules ≥2 cm

• Single imaging technique showing typical hallmarks is sufficient for definitive diagnosis 1
• Biopsy is rarely needed unless imaging features are atypical 1

Patient Population Restrictions

Non-invasive diagnostic criteria should ONLY be applied to:

• Patients with cirrhosis 1
• Patients with chronic HBV infection 1
• Patients with history of HCC 1

In all other patients without these conditions, HCC diagnosis MUST be confirmed by biopsy regardless of imaging findings. 1 This is a critical pitfall—applying non-invasive criteria to non-cirrhotic patients without chronic HBV leads to misdiagnosis of other malignancies, particularly cholangiocarcinoma. 1

Role of Biopsy

When Biopsy is Required

• Atypical imaging features that don't meet diagnostic criteria 1
• Patients without cirrhosis or chronic HBV (mandatory) 1
• Inconclusive findings after two imaging modalities 1
• LR-M category lesions on LI-RADS (suspicious for non-HCC malignancy) 1

Biopsy Standards

When performed, pathological diagnosis should follow International Consensus recommendations using required histological and immunohistochemical analyses. 1 Report tumor differentiation and HCC subtyping per WHO classification for prognostic information. 1

Simultaneously obtain non-tumoral liver parenchyma during biopsy to facilitate diagnosis. 1 This helps distinguish HCC from other hepatocellular lesions and assess background liver disease.

Role of Alpha-Fetoprotein (AFP)

AFP measurement after definitive HCC diagnosis is recommended as it provides prognostic information, but AFP should never be used alone for diagnosis. 1, 2

Key limitations of AFP:

• 35-40% of HCC cases have normal AFP levels, even with large tumors 2
• AFP ≥200 ng/mL provides high specificity (97-98%) but low sensitivity (22-49%) 2
• Elevated AFP occurs in active hepatitis, regenerating cirrhotic nodules, and other malignancies 2

Advanced Imaging Considerations

Gadoxetic acid-enhanced MRI is suggested for patients who are candidates for curative-intent treatments (transplantation, resection, ablation) as it may improve local tumor staging. 1 However, this is a weak recommendation for staging purposes, not primary diagnosis.

18F-FDG and 18F-FCH PET/CT are NOT recommended for tumor staging due to inadequate performance. 1

Common Pitfalls to Avoid

1. Do not apply non-invasive criteria to non-cirrhotic patients without chronic HBV—this leads to missed cholangiocarcinomas 1
2. Do not use AFP alone for diagnosis or screening—sensitivity is inadequate 2
3. Do not dismiss negative biopsy results if nodules show growth or changing enhancement patterns—repeat biopsy is indicated 1
4. Do not use CEUS as first-line imaging—reserve for second-line evaluation after inconclusive CT/MRI 1
5. Avoid gadoxetic acid for primary diagnosis—extracellular agents perform better for detecting washout 1