What is the initial workup and treatment approach for a liver mass?

Workup and Treatment of Liver Mass

Begin with multiphasic contrast-enhanced CT or MRI as the primary diagnostic modality, combined with AFP measurement and hepatitis panel, to establish diagnosis and guide treatment decisions based on lesion size, cirrhosis status, and enhancement pattern. 1

Initial Laboratory Workup

Essential laboratory tests include:

• Hepatitis panel: HBsAg, hepatitis B surface antibody, hepatitis B core antibody (HBcAb), HBcAb IgM (only in acute viral hepatitis), and HCV antibodies 1
• Alpha-fetoprotein (AFP): Elevated AFP >400 ng/ml in conjunction with imaging showing a growing liver mass has high positive predictive value for HCC, though AFP is elevated in only 50-75% of HCC cases 1
• Liver function tests: Bilirubin, AST, ALT, alkaline phosphatase, prothrombin time/INR, albumin, and platelet count 1
• Complete blood count, BUN, and creatinine to assess kidney function and overall status 1
• Child-Pugh classification to assess hepatic functional reserve in cirrhotic patients 1

Confirm viral load in patients testing positive for HBsAg, HBcAb IgG, or HCV antibodies, and refer to hepatology for antiviral therapy consideration. 1

Imaging Algorithm Based on Clinical Context

Cirrhotic Patients with Liver Mass

For masses >2 cm:

• If AFP >400 ng/ml OR classic arterial enhancement (hyperenhancement in arterial phase with washout in portal venous phase) on multiphasic CT or MRI, diagnose as HCC without biopsy 1
• If AFP normal and imaging atypical, obtain second dynamic imaging study (triphasic CT, contrast-enhanced ultrasound, or MRI) 1
• If two techniques show typical HCC appearance, proceed with treatment; if not, consider biopsy or resection 1

For masses 1-2 cm:

• Investigate with at least two dynamic imaging studies (triphasic CT, contrast-enhanced ultrasound, or MRI) 1
• If two techniques show typical HCC features, diagnose as HCC 1
• If atypical, perform biopsy or consider surgical resection 1

For masses <1 cm:

• Follow with ultrasound at 3-6 month intervals 1
• Biopsy recommended if nodule shows growth 1
• A growing mass with negative biopsy does not rule out HCC; continue monitoring with multidisciplinary review 1

Non-Cirrhotic Patients with Liver Mass

Initial approach:

• Measure AFP first; if elevated (>400 ng/ml) without testicular primary, confirms HCC diagnosis 1
• If AFP normal, perform multiphasic contrast-enhanced CT or MRI to characterize the lesion 1
• Search for extrahepatic primary malignancy if metastatic disease suspected 1

For indeterminate lesions on single-phase CT or noncontrast MRI:

• Multiphasic contrast-enhanced MRI is superior for characterization, with 91-95% accuracy for hemangioma, 85-93% for focal nodular hyperplasia, and 96-99% for HCC 1, 2
• For lesions ≤2 cm deemed indeterminate on CT, MRI is necessary, particularly when malignancy suspected 1, 2
• Addition of hepatobiliary phase imaging improves sensitivity for nodules <2 cm 2

Contrast-enhanced ultrasound (CEUS):

• Reduces indeterminate diagnoses from 57% to 6% 1
• Sensitivity 93-96%, specificity 75-83% for distinguishing benign versus malignant lesions 1
• Correctly characterizes 89% of focal fat, 80-90% of hemangiomas, 84-94% of FNH 1

Role of Biopsy

Avoid biopsy when:

• Lesion is potentially resectable (risk of tumor seeding) 1
• Imaging and AFP are diagnostic for HCC 1

Consider biopsy when:

• Imaging features remain indeterminate despite multiphasic CT/MRI 1, 2
• Diagnostic doubt persists after two dynamic imaging studies 1
• Patient has known extrahepatic malignancy and liver lesion nature is uncertain 1
• Non-tumor liver biopsy may be needed in non-cirrhotic patients to determine surgical approach 1

Technical success rate: 74% under grayscale ultrasound guidance, increases to 100% under CEUS guidance 1

Staging for Malignant Lesions

Required imaging:

• Chest X-ray or CT scan to detect metastatic disease 1
• CT or MRI of abdomen for complete hepatic and extrahepatic assessment 1
• CT chest and bone scintigraphy for transplant candidates 1

Additional assessments:

• US and MRI elastography to quantify cirrhosis-related fibrosis 1
• Transjugular liver biopsy with pressure measurements if needed 1

Treatment Considerations

Potentially curative options:

• Surgical resection for unifocal disease in patients with adequate hepatic reserve 1
• Liver transplantation for small volume unifocal disease, particularly in cirrhotic patients 1
• Decision between resection and transplantation depends on tumor characteristics, liver function (Child-Pugh score), and resource availability 1

For advanced HCC:

• Sorafenib is FDA-approved for unresectable hepatocellular carcinoma, with demonstrated survival benefit (median OS 10.7 vs 7.9 months, HR 0.69, p=0.00058) 3
• Appropriate for Child-Pugh Class A patients; only one Child-Pugh Class C patient was enrolled in pivotal trial 3

Common Pitfalls to Avoid

Single-phase CT is inadequate for proper characterization; multiphasic imaging is essential 2

Do not overlook patient context: underlying liver disease, history of malignancy, viral hepatitis status, and demographics significantly impact differential diagnosis 2

Rising AFP over time, even if not reaching 400 ng/ml, is virtually diagnostic of HCC 1

Imaging understages HCC (ultrasound, CT, angiography), but preoperative radiological assessment still determines prognosis for transplant selection 1

AFP can be elevated in non-malignant conditions (chronic HBV/HCV, pregnancy) and normal in up to 30% of HCC patients; imaging findings of classic enhancement are more definitive 1

Transient enhancement differences in cirrhotic livers can create artifacts mimicking lesions 2

Inadequate biopsy sampling can lead to false negatives; multiple samples increase tumor cell yield 1

Multidisciplinary evaluation including hepatology, radiology, and surgery should occur early, ideally from initial detection, to avoid redundant examinations and diagnostic delays 1, 4