What is the recommended treatment approach for a newly diagnosed hepatocellular carcinoma, considering tumor size, Child‑Pugh class, and performance status?

Treatment Approach for Newly Diagnosed Hepatocellular Carcinoma

The treatment of newly diagnosed HCC must be determined by the Barcelona Clinic Liver Cancer (BCLC) staging system, which integrates tumor burden (size, number, vascular invasion, metastases), Child-Pugh liver function class, and ECOG performance status to select the optimal therapy ranging from curative resection to best supportive care. 1, 2

Initial Staging Assessment

Before any treatment decision, you must complete the following staging workup:

• Imaging: Contrast-enhanced MRI or four-phase multidetector CT to assess tumor number, size, vascular invasion, and extrahepatic spread 1, 2
• Chest CT and bone scan in suspected advanced disease to detect metastases 1
• Child-Pugh score calculation (bilirubin, albumin, ascites, prothrombin time, encephalopathy) 1, 2
• Portal hypertension assessment: Look for esophageal varices on endoscopy, splenomegaly, and platelet count <100,000/μL; if available, measure hepatic venous pressure gradient (>10 mmHg indicates clinically significant portal hypertension) 1, 2
• ECOG performance status (0-4 scale) 1, 2
• Serum AFP level 3

Treatment Algorithm by BCLC Stage

Very Early Stage (BCLC 0): Single Tumor <2 cm

Radiofrequency ablation (RFA) is first-line treatment for tumors <2 cm in Child-Pugh A patients 4

• Surgical resection is an alternative if the patient has no cirrhosis or has Child-Pugh A with no portal hypertension and adequate future liver remnant ≥40% 1, 4
• Expected 5-year survival: 50-75% 2, 3

Early Stage (BCLC A): Single Tumor 2-5 cm or Up to 3 Tumors ≤3 cm Each

Surgical resection is the preferred first-line treatment if all of the following criteria are met 1, 2, 4:

• Child-Pugh A liver function
• No clinically significant portal hypertension (no varices, platelets ≥100,000/μL, hepatic venous pressure gradient ≤10 mmHg)
• Adequate future liver remnant ≥40% for cirrhotic liver
• Normal bilirubin

Critical pitfall: Resection in the presence of portal hypertension carries high risk of postoperative liver failure and is contraindicated 1, 2

Liver transplantation is first-line for patients who meet Milan criteria (single tumor <5 cm or ≤3 tumors ≤3 cm) but are not resection candidates due to decompensated cirrhosis, offering 3-year survival up to 88% 3, 4

RFA or microwave ablation is an alternative when surgery is not feasible due to tumor location, portal hypertension, or comorbidities 4

Intermediate Stage (BCLC B): Multinodular HCC Without Vascular Invasion or Metastases

Transarterial chemoembolization (TACE) is the standard of care if all of the following are present 1, 2, 4:

• Child-Pugh A or B7 without ascites
• ECOG performance status 0-1
• No macrovascular invasion (no portal vein thrombosis)
• No extrahepatic spread
• Limited tumor burden: solitary nodule <7 cm or ≤4 nodules 2

Expected median survival: 16 months untreated, improved with TACE 1

Critical contraindication: TACE is absolutely contraindicated in Child-Pugh C patients due to high risk of precipitating acute liver failure 2

Advanced Stage (BCLC C): Portal Vein Invasion, Nodal Involvement, or Metastases

Atezolizumab plus bevacizumab is now the first-choice standard of care for advanced HCC with preserved liver function 3, 4, 5

Sorafenib remains an alternative first-line option, extending survival by 2.8 months compared to placebo 1, 3

Eligibility criteria for systemic therapy (all must be met):

• Child-Pugh A (or favorable B7) 1, 2
• ECOG performance status 0-2 1, 2
• Adequate bilirubin and hepatic reserve 1

Expected median survival: 4-8 months untreated, improved with systemic therapy 1

Critical pitfall: Traditional cytotoxic chemotherapy (anthracyclines, cisplatin, 5-FU) shows only 10% response rate with no survival benefit and should be avoided 1, 3, 4

Terminal Stage (BCLC D): Child-Pugh C or ECOG 3-4

Best supportive care only is recommended 1, 2

Expected median survival: <4 months 1, 2

Important exception: Even in Child-Pugh C, liver transplantation should still be considered if tumor burden is within Milan criteria (single nodule ≤5 cm or ≤3 nodules ≤3 cm each), as transplantation can offer curative potential 1, 2

Systemic therapy is contraindicated in Child-Pugh C due to poor tolerance, unpredictable pharmacokinetics, and lack of efficacy data 2

Special Considerations

Child-Pugh Class Determines Treatment Eligibility

• Child-Pugh A: Eligible for all treatment modalities 1, 2
• Child-Pugh B (favorable B7): May receive TACE if no ascites, or systemic therapy if ECOG 0-1 1, 2
• Child-Pugh C: Only supportive care unless within Milan criteria for transplant 1, 2

Portal Hypertension Assessment is Critical

Portal hypertension must be evaluated independently of Child-Pugh score before considering resection 2. The presence of clinically significant portal hypertension (varices, platelets <100,000/μL, or hepatic venous pressure gradient >10 mmHg) is an absolute contraindication to resection regardless of Child-Pugh class 1, 2.

Performance Status Thresholds

• ECOG 0-1: Eligible for all therapies including resection, TACE, and systemic therapy 1, 2
• ECOG 2: May receive systemic therapy but not resection or TACE 1
• ECOG 3-4: Best supportive care only 2

Post-Treatment Surveillance

After curative resection or ablation, perform AFP measurement and dynamic CT or MRI every 3-6 months for at least 2 years, as recurrence rates reach 50-60% at 5 years and repeat curative interventions may be feasible 3, 4

No adjuvant therapy has proven benefit after resection or ablation 3

Common Pitfalls to Avoid

1. Do not perform resection in patients with portal hypertension—this leads to postoperative liver failure 1, 2
2. Do not use TACE in Child-Pugh C patients—risk of precipitating acute liver failure 2
3. Do not use traditional chemotherapy (anthracyclines, cisplatin, 5-FU)—no survival benefit and poor tolerance 1, 3, 4
4. Do not give systemic therapy to Child-Pugh C patients outside of clinical trials—no efficacy data and poor tolerance 2
5. Do not deny transplant evaluation to Child-Pugh C patients within Milan criteria—transplant can still be curative 1, 2