What is the management approach for Hepatocellular Carcinoma (HCC) in a patient with liver cirrhosis?

Management of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

The management of hepatocellular carcinoma (HCC) in cirrhotic patients should follow the Barcelona Clinic Liver Cancer (BCLC) staging system, which incorporates tumor burden, liver function, and performance status to guide treatment decisions. 1, 2

Diagnosis and Staging

• Diagnosis of HCC in cirrhotic patients can be made non-invasively through characteristic imaging findings; however, lesional biopsy should be considered if radiological criteria are not fulfilled 1
• Pathological confirmation is necessary in non-cirrhotic patients and when systemic therapy is being considered 1
• The BCLC staging system is the most widely validated and recommended system for prognostication and treatment allocation 1, 2

Treatment Options by BCLC Stage

Very Early (BCLC 0) and Early Stage (BCLC A)

• Surgical resection is the preferred first-line treatment for:

  • HCC in non-cirrhotic liver 1
  • Solitary HCC in cirrhotic liver when liver function is maintained and adequate remnant liver volume can be preserved 1
  • Assessment for resection requires evaluation of liver function, portal hypertension, extent of hepatectomy, and future liver remnant 1

• Liver transplantation is recommended for:

  • Patients with decompensated cirrhosis and HCC within accepted criteria 1, 2
  • Multifocal HCC within accepted criteria 1
  • As a second-line treatment for solitary <2 cm HCC in compensated cirrhosis when technical/anatomical considerations limit first-line treatments 1
  • Patients listed for transplant should receive neoadjuvant locoregional therapy while waiting to prevent disease progression 1, 2

• Thermal ablation is recommended for:

  • Selected patients with solitary <2 cm HCC in compensated cirrhosis 1
  • As an alternative first-line treatment to surgery for solitary tumors 2-3 cm in size 1

Intermediate Stage (BCLC B)

• Transarterial chemoembolization (TACE) is standard of care for patients with:
  • Multifocal HCC
  • Preserved liver function
  • No vascular invasion or extrahepatic spread 2

Advanced Stage (BCLC C)

• Systemic therapy is the mainstay of treatment:
  • Atezolizumab plus bevacizumab is currently the preferred first-line treatment 2, 3
  • Lenvatinib is an FDA-approved option for first-line treatment of unresectable HCC 4
  • Sorafenib remains an option for patients with contraindications to immunotherapy 2, 3

End-Stage (BCLC D)

• Best supportive care is recommended for patients with:
  • Child-Pugh C cirrhosis
  • HCC exceeding transplant criteria 2

Special Considerations

• Contraindications for liver transplantation include:

  • Tumor-related vascular invasion
  • Extrahepatic metastases 1

• Adjuvant therapy with atezolizumab and bevacizumab improves recurrence-free survival after resection, though longer-term follow-up is required 1, 2

• Downstaging may be considered for patients with tumor burden beyond accepted criteria, though no definitive recommendation can be made regarding expanded criteria 1, 2

Monitoring and Follow-up

• Regular monitoring of liver function is essential during treatment, particularly with systemic therapies like lenvatinib that can cause hepatotoxicity 4
• Patients receiving systemic therapy should be monitored for specific side effects, including hypertension, cardiac dysfunction, and proteinuria 4

Pitfalls and Caveats

• Treatment decisions must balance oncological outcomes with preservation of liver function, as aggressive treatments may precipitate hepatic decompensation 5, 6
• The multidisciplinary approach is crucial for optimal management, involving hepatologists, oncologists, interventional radiologists, and transplant surgeons 7, 8
• Most clinical trials for systemic therapy enrolled only Child-Pugh A patients, making evidence-based recommendations for Child-Pugh B/C patients challenging 3