What is the initial approach to treating hepatocellular disease?

Initial Approach to Treating Hepatocellular Disease

The initial approach to treating hepatocellular disease should focus on prevention of disease progression to cirrhosis through treatment of the underlying liver disease, followed by appropriate staging and selection of therapy based on tumor burden, liver function, and patient performance status if hepatocellular carcinoma (HCC) has developed. 1

Prevention and Early Management

• Therapy for the underlying liver disease to prevent progression to cirrhosis is the best approach for prevention of HCC, particularly in the developed world 1
• For hepatitis B, universal vaccination at birth has shown a decrease in HCC rates, and antiviral nucleoside analogues in patients with cirrhosis due to HBV have demonstrated decreased rates of HCC 1
• For hepatitis C, effective antiviral therapy can eradicate the virus and resolve chronic liver disease in approximately half of patients, potentially decreasing HCC risk 1
• Abstinence is usually effective in reversing alcoholic liver disease, and phlebotomy is effective in hemochromatosis for preventing progression of liver disease 1
• Antiviral therapy with nucleoside or nucleotide analogues for HBV and combination peginterferon alfa 2a plus ribavirin for HCV is recommended to reduce HCC risk 1

Surveillance in High-Risk Groups

• Surveillance for HCC should be considered in high-risk groups including:

  • Males and females with established cirrhosis due to HBV, particularly those with ongoing viral replication 1
  • Males and females with established cirrhosis due to HCV 1
  • Males and females with established cirrhosis due to genetic hemochromatosis 1
  • Males with alcohol-related cirrhosis who are abstinent or likely to comply with treatment 1
  • Males with cirrhosis due to primary biliary cirrhosis 1

• Surveillance should consist of six-monthly abdominal ultrasound assessments in combination with serum alpha-fetoprotein (AFP) estimation 1

Diagnosis and Staging

• A focal lesion in the liver of a patient with cirrhosis is highly likely to be HCC 1
• Initial assessment should be by spiral computed tomography (CT) of the liver and thorax 1
• Magnetic resonance imaging (MRI) with contrast enhancement may increase the accuracy of detection 1
• Biopsy is rarely required for diagnosis and should be avoided for potentially operable lesions due to 1-3% risk of tumor seeding 1
• Staging should incorporate both tumor burden and liver function, with the Barcelona Clinic Liver Cancer (BCLC) classification being widely used 1

Treatment Algorithm Based on Disease Stage

Early Stage HCC (BCLC 0-A)

• Curative options should be considered first:
  • Liver transplantation for patients with cirrhosis and small HCC (≤5 cm single nodule or up to three lesions ≤3 cm) 1
  • Hepatic resection for patients with HCC and non-cirrhotic liver or highly selected patients with Child-Pugh A cirrhosis 1
  • Percutaneous ablation (radiofrequency ablation or ethanol injection) for small non-surgical HCC, particularly nodules <2 cm 1

Intermediate Stage HCC (BCLC B)

• Transarterial chemoembolization (TACE) is recommended as first-line non-curative therapy for non-surgical patients with large/multifocal HCC who do not have vascular invasion or extrahepatic spread 1
• TACE can improve survival by 20% to 60% at 2 years compared to untreated patients 1

Advanced Stage HCC (BCLC C)

• Systemic therapy with sorafenib is recommended for patients with advanced disease (portal invasion, nodal involvement, or metastases) with preserved liver function (Child-Pugh A) 1
• Newer options including immune checkpoint inhibitor-based therapies may be considered based on recent evidence 2

Terminal Stage HCC (BCLC D)

• Symptomatic treatment and best supportive care are recommended 1

Special Considerations

• Treatment decisions should be made in a multidisciplinary setting, incorporating tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences 2
• The fibrolamellar variant is not associated with cirrhosis, does not have elevated AFP, and if resectable, has a more favorable prognosis 1
• Patients with replicating HBV should receive effective antiviral therapy when being assessed for transplantation 1
• Tenofovir treatment in chronic hepatitis B can help prevent progression to HCC, though the relationship between treatment response and long-term prevention of outcomes such as HCC is not fully established 3

Common Pitfalls to Avoid

• Delaying treatment of underlying liver disease, as early intervention is more effective in preventing progression to cirrhosis and HCC 1
• Performing biopsy on potentially operable lesions, which carries a risk of tumor seeding 1
• Overlooking the need for multidisciplinary evaluation, as treatment decisions require input from hepatologists, surgeons, interventional radiologists, and oncologists 2
• Failing to consider liver transplantation for patients with poor liver synthetic function (Child-Pugh C) but tumor extent within Milan criteria 1