What are the diagnostic and treatment approaches for a patient presenting with symptoms of Hepatocellular Carcinoma (HCC)?

Hepatocellular Carcinoma: Clinical Presentation and Symptoms

HCC is often asymptomatic in early stages and typically presents with symptoms only when disease is advanced, including right upper quadrant pain, weight loss, early satiety, abdominal distension from ascites, jaundice, and signs of hepatic decompensation in the setting of underlying cirrhosis. 1, 2

Common Clinical Presentations

Early-Stage Disease

• Most patients are asymptomatic and HCC is detected through surveillance programs in high-risk populations (cirrhotic patients, chronic HBV carriers) 3, 4
• Any deterioration in liver function in a patient with known cirrhosis should raise immediate suspicion for HCC 4
• Surveillance with ultrasound every 6 months plus AFP detects early-stage disease in 63% of cases when combined, versus only 45% with ultrasound alone 4

Advanced-Stage Symptoms

• Right upper quadrant or epigastric pain from hepatic capsular distension or tumor rupture 1
• Weight loss and cachexia are common presenting features in advanced disease 1
• Fatigue occurs frequently and significantly impacts quality of life 1
• Early satiety from mass effect or ascites 1

Obstructive Syndromes

• Ascites develops from portal hypertension, hepatic decompensation, or peritoneal carcinomatosis 1
• Jaundice indicates either biliary obstruction from tumor or advanced hepatic dysfunction 1
• Portal vein thrombosis from tumor invasion causes acute worsening of portal hypertension 3

Physical Examination Findings

Hepatic Signs

• Hepatomegaly with palpable right upper quadrant mass in larger tumors 1
• Hepatic bruit (rare but specific finding) 1
• Signs of chronic liver disease: spider angiomata, palmar erythema, gynecomastia 1

Decompensation Signs

• Ascites with shifting dullness or fluid wave 1
• Peripheral edema from hypoalbuminemia 1
• Jaundice and scleral icterus 1
• Hepatic encephalopathy (asterixis, altered mental status) in advanced cases 1

Diagnostic Approach When Symptoms Present

Initial Evaluation

• Obtain AFP level immediately: AFP ≥200 ng/mL provides 97-98% specificity for HCC diagnosis in patients with a liver mass, though sensitivity is only 22-49% 4
• Order multiphasic CT or dynamic contrast-enhanced MRI to characterize any hepatic lesion 3, 4
• Assess liver function using Child-Pugh classification, as this determines treatment eligibility and prognosis 3, 5

Imaging Interpretation by Nodule Size

• Nodules <1 cm: Follow with ultrasound at 3-6 month intervals; do not proceed to advanced imaging or biopsy 4
• Nodules 1-2 cm: Obtain at least two dynamic imaging studies; if both show typical HCC appearance (arterial hypervascularity with portal/delayed phase washout), diagnose HCC without biopsy 4
• Nodules >2 cm: A single dynamic imaging study showing typical HCC features is diagnostic and does not require biopsy 4, 5
• Mass >2 cm with AFP >400 ng/mL in cirrhotic patient: This combination is diagnostic without requiring biopsy 5

Staging Workup

• Chest imaging (CT preferred for transplant candidates) to detect pulmonary metastases 4, 5
• Complete abdominal imaging to assess tumor burden, vascular invasion, and extrahepatic spread 4, 5
• Bone scintigraphy for transplant candidates 4
• Use BCLC staging system rather than TNM alone, as it incorporates liver function and determines treatment strategy 3, 4, 5

Prognostic Implications of Symptoms

Poor Prognostic Indicators

• Vascular invasion indicates aggressive biology and significantly worsens prognosis, requiring systemic therapy rather than locoregional treatment 5
• Symptoms at presentation generally indicate advanced-stage disease with 5-year survival <10%, compared to 50-75% for asymptomatic early-stage disease 5
• Child-Pugh class C (severe hepatic dysfunction) limits treatment to supportive care only 3
• Performance status decline from tumor burden eliminates candidacy for systemic therapy 5

Treatment Implications Based on Presentation

• Asymptomatic early-stage (BCLC 0-A): Surgical resection, ablation, or transplantation offer curative potential 3, 4
• Symptomatic intermediate-stage (BCLC B): Transarterial chemoembolization is standard of care 3, 5
• Symptomatic advanced-stage (BCLC C): Atezolizumab plus bevacizumab is the preferred first-line systemic therapy 4, 5
• End-stage with heavily impaired liver function or poor performance status: Only symptomatic/supportive care is appropriate 3

Critical Pitfalls to Avoid

• Never rely on AFP alone for diagnosis or screening—up to 35-40% of HCC cases have normal AFP even with large tumors 4
• Do not biopsy lesions when non-invasive criteria are met (nodule >2 cm with typical imaging features in cirrhotic liver), as this adds risk without benefit 3, 4
• Do not delay imaging in cirrhotic patients with new symptoms or clinical deterioration—this may represent HCC development 4
• Avoid treating Child-Pugh C patients with anything beyond supportive care, as they cannot tolerate active therapies 3