What is hepatocellular disease?

Hepatocellular Carcinoma: Definition, Diagnosis, and Management

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver in adults, characterized by cancerous cells that resemble normal hepatocytes and typically develops in the setting of chronic liver disease and cirrhosis.

Definition and Epidemiology

Hepatocellular carcinoma represents a significant global health burden:

• It is the fifth most common cancer worldwide and the third leading cause of cancer-related death 1
• The incidence varies from 3/100,000 in Western countries to over 15/100,000 in regions with high hepatitis B and C prevalence 1
• Incidence is rising steadily in the United States and other Western countries 1
• Shows strong male preponderance and increases with advancing age 1
• In Europe, the estimated incidence rate in 2012 was 10.0 in men and 3.3 in women per 100,000 1

Etiology and Risk Factors

HCC develops primarily in the context of chronic liver disease:

• Viral hepatitis:

  • Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most important causes 1
  • HBV accounts for approximately 50% of all cases worldwide 2
  • HCV accounts for approximately 25% of cases 2

• Other major risk factors:

  • Alcoholic liver disease 1
  • Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) 1
  • Aflatoxin B1 exposure, particularly in HBV-infected individuals 1
  • Hereditary hemochromatosis and iron overload 3
  • Other chronic liver diseases: autoimmune hepatitis, Wilson disease, primary biliary cirrhosis, α1-antitrypsin deficiency 3

• Important note: In less than 10% of cases, HCC occurs in an otherwise normal liver 1

Pathogenesis

HCC typically develops through a multi-step process:

• In cirrhotic livers, regenerative nodules can progress to dysplastic nodules and eventually to HCC 1
• HCC may also evolve from subclasses of adenomas 1
• The cell of origin remains uncertain - may be either liver stem cells or mature hepatocytes 1
• Fibrolamellar HCC is a rare variant occurring in young patients without risk factors, with better prognosis 1

Diagnosis

The diagnosis of HCC relies on a combination of clinical, laboratory, imaging, and pathological examinations:

• Imaging studies:

  • Dynamic (multiple phase) MRI or CT studies are the cornerstone of diagnosis 1
  • Characteristic vascular pattern: early arterial enhancement and washout in portal and late phases 4
  • MRI has higher sensitivity than CT, especially for small lesions 4

• Laboratory tests:

  • Alpha-fetoprotein (AFP) can be elevated but is not specific 1
  • In cirrhotic patients with AFP >500 mg/ml, diagnosis may be made without biopsy 1
  • Liver function tests to assess underlying liver disease 1

• Pathological diagnosis:

  • Liver biopsy remains the gold standard for definitive diagnosis 1
  • Fine-needle aspiration cytology is an option when biopsy is not possible 1
  • Immunohistochemistry may help differentiate HCC from other liver tumors 1

Staging and Classification

Several staging systems exist for HCC, with the Barcelona Clinic Liver Cancer (BCLC) system being widely used:

• BCLC staging:

  • Stage 0-A: Early disease, potentially curable
  • Stage B: Intermediate disease
  • Stage C: Advanced disease with vascular invasion or extrahepatic spread
  • Stage D: End-stage disease 4

• Assessment should include:

  • Tumor extent (number and size of nodules, vascular invasion)
  • Liver function (Child-Pugh score)
  • Patient performance status 1

Management

Treatment options depend on tumor stage, liver function, and patient performance status:

• Potentially curative treatments (for early-stage HCC):

  • Surgical resection: For patients with single tumors and well-preserved liver function 5
  • Liver transplantation: For patients with decompensated cirrhosis and limited tumor burden 5
  • Local ablation (radiofrequency ablation, alcohol injection): Can be curative for small tumors 5

• Palliative treatments (for intermediate to advanced HCC):

  • Transarterial chemoembolization (TACE): For intermediate-stage HCC 4
  • Systemic therapy: Sorafenib is the standard first-line treatment for advanced HCC with well-preserved liver function 4, 6
  • Supportive care: For end-stage disease 4

Prevention and Surveillance

Prevention strategies are critical given the strong association with chronic liver disease:

• Primary prevention:

  • Universal vaccination against hepatitis B at birth 1
  • Early antiviral treatment of HBV and HCV 1
  • Reduction of alcohol consumption 1
  • Promotion of healthy lifestyle to prevent NAFLD/NASH 1

• Surveillance:

  • Recommended for all cirrhotic patients 1
  • Abdominal ultrasound every 6 months 1
  • Early detection increases the chance of curative treatment 7

Prognosis

The prognosis of HCC varies widely depending on stage at diagnosis and treatment options:

• Early-stage HCC treated with curative intent can achieve 5-year survival rates >50% 5
• Advanced HCC has a poor prognosis, with median survival of approximately 10.7 months with sorafenib treatment versus 7.9 months with placebo 6
• Treatment of underlying liver disease can reduce the risk of HCC development 3

HCC remains a challenging disease with rising incidence worldwide, but early detection through surveillance programs and advances in treatment options offer hope for improved outcomes.