What is the initial workup for a patient suspected of having liver carcinoma?

Initial Workup for Suspected Liver Carcinoma

Begin with a comprehensive multidisciplinary evaluation that includes history and physical examination focusing on chronic liver disease risk factors, laboratory assessment with hepatitis panel and AFP, multiphasic contrast-enhanced CT or MRI, and liver function assessment using Child-Pugh classification. 1, 2

History and Clinical Assessment

Obtain detailed history focusing on:

• Risk factors for chronic liver disease: intravenous drug use, alcohol intake, viral hepatitis exposure 1
• Signs and symptoms of chronic liver disease: jaundice, ascites, encephalopathy, splenomegaly 1
• Performance status and nutritional state 1

Any deterioration in liver function in a patient with known cirrhosis should raise suspicion for HCC. 1

Laboratory Evaluation

Essential Initial Tests

• Hepatitis panel: HBsAg, hepatitis B surface antibody, hepatitis B core antibody (HBcAb), HBcAb IgM (only in acute viral hepatitis), and HCV antibodies 1
• Serum alpha-fetoprotein (AFP): AFP >400 ng/ml can establish diagnosis without biopsy in cirrhotic patients with appropriate imaging findings 1
• Liver function tests: bilirubin, AST, ALT, alkaline phosphatase, prothrombin time/INR, albumin 1
• Complete blood count with platelet count (surrogate marker for portal hypertension) 1
• Renal function: BUN and creatinine (prognostic marker in liver disease) 1

Important caveat: AFP is elevated in only 50-75% of HCC cases, so normal AFP does not exclude the diagnosis. 1

Viral Load Confirmation

If HBsAg, HBcAb IgG, or HCV antibodies are positive, confirm viral load and refer to hepatology for antiviral therapy consideration. 1

Imaging Studies

Primary Diagnostic Imaging

Multiphasic contrast-enhanced CT or MRI is the primary diagnostic modality. 2

• Initial imaging: Triphasic (multiphasic) CT scan or MRI of the abdomen showing arterial, portal venous, and delayed phases 1, 2
• Chest imaging: Chest X-ray or CT scan to evaluate for metastases 1

MRI has superior sensitivity and specificity compared to CT in nodular cirrhotic livers, though overall sensitivity is similar. 1

Size-Based Diagnostic Algorithm

For nodules <1 cm in cirrhotic liver:

• Follow with ultrasound at 3-6 month intervals 1, 3

For nodules 1-2 cm in cirrhotic liver:

• Investigate with at least two dynamic studies (triphasic CT, contrast ultrasound, or MRI) 1, 3
• If two techniques show typical HCC appearance, diagnose as HCC without biopsy 1
• If findings are atypical, proceed to biopsy or surgical excision 1

For nodules >2 cm with typical HCC features:

• Diagnose as HCC without biopsy if typical arterial enhancement pattern is present on dynamic imaging 1, 3
• Also diagnose as HCC without biopsy if AFP >400 ng/ml in cirrhotic patients with focal hypervascular lesion 1, 2

Assessment of Liver Function and Portal Hypertension

Child-Pugh Classification

Calculate using:

• Serum albumin
• Bilirubin
• Prothrombin time/INR
• Clinical assessment of encephalopathy
• Clinical assessment of ascites 1

This classifies patients as Child-Pugh A (compensated) or B/C (decompensated), which determines treatment eligibility. 1

Portal Hypertension Assessment

• Upper endoscopy: evaluate for esophageal varices and hypertensive gastropathy 1
• Cross-sectional imaging findings: splenomegaly, splenorenal shunts, recanalization of umbilical vein, thrombocytopenia 1
• Optional: transjugular measurement of hepatic-venous pressure gradient 1

Role of Biopsy

Avoid biopsy in the following situations:

• Potentially resectable lesions with diagnostic imaging and/or AFP >400 ng/ml 1, 2
• Patients with AFP >400 ng/ml and potentially resectable mass should proceed directly to surgery 1

Biopsy carries 1-3% risk of tumor seeding in the needle tract. 1

Consider biopsy when:

• Imaging features remain indeterminate despite multiphasic CT/MRI 2
• Diagnostic doubt persists after two dynamic imaging studies 1
• Patient has known extrahepatic malignancy and liver lesion nature is uncertain 2

Critical pitfall: A growing mass with negative biopsy does not rule out HCC; continue monitoring with multidisciplinary review. 1

Staging Workup

Once HCC is diagnosed, complete staging includes:

• Chest CT (or chest X-ray as alternative) 1
• Abdominal CT or MRI (already obtained for diagnosis) 1
• For transplant candidates: chest CT and bone scintigraphy 1

Use BCLC (Barcelona Clinic Liver Cancer) or CLIP (Cancer of the Liver Italian Program) staging systems, which incorporate both tumor characteristics and underlying liver disease severity. 1

Multidisciplinary Evaluation

Early multidisciplinary evaluation including hepatology, radiology, and surgery should occur from initial detection to avoid redundant examinations and diagnostic delays. 2 This is particularly important as 75% of HCC cases are multifocal at diagnosis. 1