Hepatocellular Carcinoma

Hepatocellular Carcinoma

 

Hepatocellular carcinoma (HCC) is one of the most common tumors in the world, particularly in populations with chronic viral hepatitis and Asian or Sub-Saharan African ancestry.

Epidemiology

  • Incidence
    • 2.4/100,000
    • 18,000 cases each year in the U.S.
    • 5th most common cancer worldwide
  • Age – peaks in 50-60 year olds in U.S. (in Asian countries, 20-50 year olds)
  • Sex – M>F (3:1 in populations with a high prevalence of HCC)
  • Ethnicity – higher incidence in Asian or African populations

Risk Factors

  • Cirrhosis (90% of cases)
    • Infectious – chronic hepatitis B (HBV), C (HCV) or D (HDV)
      • HBV accounts for majority of HCC in China and Africa
      • HCV accounts for majority of HCC in Western hemisphere
    • Heavy alcohol consumption
      • >80 gm/day for >10 years increases risk for HCC 5-fold
    • Autoimmune diseases
      • Autoimmune hepatitis
      • Primary biliary cirrhosis
    • Hereditary metabolic liver diseases
      • Alpha-1-antitrypsin deficiency
      • Hemochromatosis
      • Hereditary tyrosinemia
      • Porphyria cutanea tarda
      • Glycogen storage diseases
    • Non-alcoholic steatohepatitis (NASH)
    • Highest risk in chronic hepatitis and alcohol-induced cirrhosis
  • Toxins
    • Aflatoxin B1 – produced by Aspergillus species that contaminate grains and nuts in China and Africa
    • Long term androgenic steroid administration
    • Vinyl chloride exposure
    • Tobacco
  • Coexistence of risk factors increases the risk of HCC

Pathophysiology

  • Usually hepatocyte malignancy
    • Variants include pleomorphic cell, clear cell, sarcomatous, fibrolamellar or undifferentiated
    • Other tumors (cholangiocarcinoma and angiosarcoma)

Clinical Presentation

  • Most patients have a past history of chronic liver disease or cirrhosis
  • Abdominal pain – usually right upper quadrant, friction rub or bruit over liver, abdominal mass, hepatomegaly, ascites
  • Constitutional manifestations – anorexia, malaise, weight loss
  • Jaundice
  • Paraneoplastic syndromes (20%)
    • Acquired porphyria
    • Cryofibrinogenemia
    • Diarrhea (vasoactive intestinal polypeptide)
    • Erythrocytosis (erythropoietin-like activity)  
    • Hypercalcemia (parathyroid-like hormone)
    • Hypercholesterolemia
    • Hypoglycemia (insulin growth factor)
    • Polymyositis
  • Degree of underlying cirrhosis impacts survival; general prognosis is very poor (5 year survival <50%)
    • Barcelona Clinic Liver Cancer System is the best at stratifying for survival (for more information, refer to Sala, 2005)

Diagnosis

  • Indications for testing - clinical symptoms in the presence of risk factors; elevated markers
  • Biopsy – histopathology of tissue sample is diagnostic
  • Imaging – ultrasound, CT/MRI

Disease Monitoring

  • Markers
    • Alpha fetoprotein (AFP)-L3%
      • Specificity for HCC is >90%
      • May be predictive of tumor aggressiveness
      • Elevated AFP-L3% is associated with a seven-fold increase in the risk of developing HCC within the next 21 months in a patient who does not currently have HCC but has chronic liver disease
    • Alpha fetoprotein (AFP)
      • Less specific than AFP-L3%
    • Des-gamma-carboxy prothrombin (DCP)
      • Complements hepatocellular carcinoma markers AFP or AFP-L3% in surveillance and risk assessment for hepatocellular carcinoma
      • Useful marker for following patients with HCC after therapy if they were positive prior to therapy
      • Elevated DCP is associated with an increased risk for developing hepatocellular carcinoma
    • TP53 mutations are under investigation at this time

Disease Screening

  • No guidelines exist which demonstrate routine screening changes outcome
    • Most liver centers use routine surveillance (every 6 months)
    • Screening generally includes tumor markers and imaging (combination of AFP-L3%, des-gamma-carboxy prothrombin, ultrasound)

Prevention

  • Hepatitis B vaccination markedly reduces infection rate
  • Interferon-based therapies to reduce rate of hepatitis-induced cirrhosis for hepatitis B and C
  • Effective iron depletion for patients with hemochromatosis
  • Liver transplantation in hereditary tyrosinemia
  • Elimination of hepatotoxin exposure (alcohol, aflatoxin)

See Also