Which laboratory studies are indicated to assess for hepatocellular carcinoma in a patient with a hepatic mass?

Laboratory Work-Up for Suspected Hepatocellular Carcinoma

When evaluating a patient with a hepatic mass for possible hepatocellular carcinoma, obtain serum alpha-fetoprotein (AFP), complete liver function tests (prothrombin time, albumin, bilirubin), complete blood count with platelets, and viral hepatitis serologies (HBsAg, anti-HBc, anti-HCV). 1

Essential Laboratory Studies

Tumor Marker Assessment

• Serum alpha-fetoprotein (AFP) is the primary tumor marker for HCC evaluation 1
• AFP ≥200 ng/mL combined with typical imaging features allows diagnosis without biopsy in cirrhotic patients 2, 3
• AFP ≥400 ng/mL has 100% specificity for HCC in cirrhotic patients with hepatic masses 1, 3
• Critical limitation: AFP is elevated in only 40-60% of HCC cases, with particularly poor sensitivity (32-50%) in early-stage disease 2
• Up to 46% of HCC patients have completely normal AFP (<20 ng/mL), so normal values do not exclude HCC 2
• Rising AFP in a step-wise pattern strongly suggests HCC even when absolute values remain below diagnostic thresholds 2

Liver Function Assessment

• Prothrombin time (or INR) to assess synthetic function 1
• Serum albumin to evaluate hepatic synthetic capacity and nutritional status 1
• Total and direct bilirubin to assess hepatic excretory function 1
• These parameters are essential for Child-Pugh classification, which determines treatment eligibility 1

Hematologic Studies

• Complete blood count including platelet count to assess for cytopenias related to portal hypertension and hypersplenism 1
• Thrombocytopenia often indicates advanced cirrhosis with portal hypertension 1

Etiology Determination

• Hepatitis B serologies: at minimum HBsAg and anti-HBc 1
• Hepatitis C serology: anti-HCV antibody 1
• Iron studies to evaluate for hemochromatosis 1
• Autoimmune markers if autoimmune hepatitis is suspected 1

Algorithmic Approach to AFP Interpretation

For Cirrhotic Patients with Hepatic Mass:

• AFP ≥400 ng/mL: Proceed directly to treatment planning without biopsy if imaging shows typical features 1, 3
• AFP 200-399 ng/mL: Diagnosis can be established without biopsy if dynamic CT or MRI shows arterial hypervascularity with venous/delayed phase washout 2, 3
• AFP <200 ng/mL: Diagnosis relies primarily on imaging characteristics; biopsy may be needed if imaging is atypical 1

For Non-Cirrhotic Patients:

• Any hepatic mass requires tissue diagnosis regardless of AFP level, as the vascular profile may not be characteristic 3
• Elevated AFP without typical imaging features mandates biopsy to exclude other malignancies 3

Common Pitfalls to Avoid

Do not rely on AFP alone for diagnosis - AFP has poor sensitivity (39-65%) and will miss 30-59% of HCC cases even at the commonly used 20 ng/mL cutoff 2

Do not dismiss the diagnosis with normal AFP - Nearly half of HCC patients have normal AFP levels, particularly in early-stage disease 2

Do not ignore AFP trends - A progressively rising AFP (≥7 ng/mL/month) has 71.4% sensitivity and 100% specificity for HCC, even when absolute values remain below diagnostic thresholds 2

Do not perform biopsy on potentially resectable lesions when AFP and imaging are diagnostic - this risks tumor seeding in the needle tract (1-3% incidence) 1, 3

Do not forget to assess liver function - Treatment decisions depend equally on tumor characteristics and hepatic reserve; Child-Pugh grade C patients should receive only supportive care 1

Additional Considerations

Portal Hypertension Assessment

While not strictly "laboratory" work, the diagnostic work-up should include 1:

• Upper endoscopy to evaluate for esophageal varices and hypertensive gastropathy
• Optional transjugular hepatic venous pressure gradient measurement in selected cases

Surveillance Context

For patients in HCC surveillance programs, the combination of ultrasound plus AFP every 6 months increases early-stage detection from 45% to 63% compared to ultrasound alone 2, 4

The laboratory evaluation provides critical information for diagnosis, staging, and treatment planning, but must always be interpreted in conjunction with imaging findings and clinical context 1