What is the workup for suspected hepatocellular carcinoma (HCC)?

Diagnostic Workup for Suspected Hepatocellular Carcinoma (HCC)

The diagnostic workup for suspected hepatocellular carcinoma should include a comprehensive evaluation with dynamic imaging studies (multiphasic CT or MRI), laboratory tests including alpha-fetoprotein (AFP), and assessment of liver function, with biopsy reserved for inconclusive cases. 1

Initial Evaluation

History and Clinical Examination

• Assess risk factors for chronic liver disease:
  • Viral hepatitis (HBV, HCV)
  • Alcohol consumption
  • Metabolic syndrome (obesity, diabetes)
  • IV drug use history 2, 1
• Evaluate signs and symptoms of chronic liver disease:
  • Jaundice, ascites, encephalopathy
  • Splenomegaly
  • Performance status and nutritional state 2, 1

Laboratory Analysis

• Liver etiology workup:
  • HBV serology (HBsAg, anti-HBc)
  • HCV serology (anti-HCV)
  • Iron studies
  • Autoimmune markers 2, 1
• Liver function assessment:
  • Prothrombin time
  • Albumin
  • Bilirubin
  • Complete blood count including platelets 2, 1
• Tumor marker:
  • Serum alpha-fetoprotein (AFP) - elevated >400 ng/ml is highly suggestive of HCC in cirrhotic patients 2, 1

Imaging Studies

Primary Imaging

• Dynamic (multiphasic) contrast-enhanced MRI or CT scan 2, 1
  • Evaluates tumor extent within the liver
  • Assesses number and size of nodules
  • Detects vascular invasion
  • Identifies extrahepatic spread

Diagnostic Algorithm Based on Nodule Size in Cirrhotic Patients

• Nodules <1 cm: Follow with ultrasound every 3-6 months 1
• Nodules 1-2 cm: Investigate with at least two dynamic imaging studies 1
• Nodules >2 cm with typical HCC features on dynamic imaging OR any nodule with AFP >400 ng/ml: Can be considered proven HCC without biopsy 2, 1

Additional Imaging for Staging

• Chest CT to evaluate for metastases 2, 1
• Consider bone scan in advanced disease 2, 1

Portal Hypertension Assessment

• Upper endoscopy to identify varices and/or hypertensive gastropathy 2, 1
• Optional: Transjugular measurement of hepatic venous pressure gradient 2

Biopsy Considerations

• Generally not required if imaging is characteristic in cirrhotic patients 1
• Should be performed when:
  • Imaging findings are inconclusive
  • Diagnosis is needed in non-cirrhotic liver
  • Required for clinical trials 2, 1
• Caution: Avoid biopsy in potentially operable lesions due to risk of tumor seeding 1

Staging Systems

• TNM/AJCC staging criteria for tumor classification 2, 1
• Barcelona Clinic Liver Cancer (BCLC) staging for treatment planning 1
• Child-Pugh score to assess underlying liver function 2, 1

Common Pitfalls and Caveats

1. Relying solely on AFP: While elevated AFP (>400 ng/ml) is suggestive of HCC, it's only elevated in 50-75% of cases. Normal AFP does not exclude HCC 1, 3

2. Missing non-cirrhotic HCC: While most HCCs occur in cirrhotic livers, up to 10% can develop in non-cirrhotic livers, particularly in NAFLD/NASH patients 2, 4

3. Inadequate imaging technique: Dynamic multiphasic imaging is essential for accurate diagnosis. Single-phase studies may miss the characteristic enhancement pattern of HCC 2, 1

4. Neglecting staging workup: Complete staging with chest CT and consideration of bone scan in advanced disease is crucial for treatment planning 2, 1

5. Inappropriate biopsy timing: Biopsy should be avoided in potentially resectable lesions when imaging is diagnostic, as it carries risk of tumor seeding 1

The diagnostic approach to HCC has evolved significantly, with non-invasive criteria now allowing diagnosis without biopsy in many cirrhotic patients. However, a systematic approach using appropriate imaging techniques and laboratory tests remains essential for accurate diagnosis and staging, which directly impacts treatment options and patient outcomes.