Hepatocellular Carcinoma (HCC)

Snapshot

• A 65-year-old man presents to his primary care physician for right upper quadrant abdominal pain. He was diagnosed with hepatitis C infection, complicated by hepatic cirrhosis. Abdominal ultrasound demonstrates a focal hepatic lesion. He underwent a multi-phase contrasted abdominal CT scan, which demonstrated an enhancing focal hepatic mass during the arterial phase with rapid washout during the portal venous phase.

Introduction

• Overview
  • primary malignancy affecting hepatocytes 
  • may result in a paraneoplastic syndrome
    • hypoglycemia
    • erythrocytosis
    • hypercalcemia
    • severe diarrhea
    • EPO, insulin-like growth factor, and PTHrP 
• Epidemiology
  • risk factors
    • cirrhosis (80-90% of cases)
    • chronic hepatitis B infection
    • chronic hepatitis C infection
    • aflatoxin, produced by Aspergillus species
    • alcohol use
    • hereditary hemochromatosis
    • α1-antitrypsin deficiency
    • obesity
    • diabetes mellitus
    • non-alcoholic fatty liver disease
• Pathophysiology
• β-catenin activation and inhibition of p53 play a role in the development of hepatocellular carcinoma

Presentation

• Symptoms/physical exam
  • right upper quadrant pain
  • weight loss
  • ascites
  • obstructive jaundice
• however, patients can be asymptomatic and be incidentally found to have HCC due to routine screening in patients with cirrhosis

Imaging

• Abdominal ultrasound
  • indication
    • monitoring lesions < 1 cm every 3-6 months for up to 2 years 
    • can be used as a screening imaging study in patients with cirrhosis
      • if there are findings concerning for HCC, then confirmatory imaging (or possibly biopsy) is needed 
  • findings
    • masses with poorly defined margins
    • irregular echoes
• Multi-phase contrasted CT abdomen
  • indication
    • a confirmatory imaging study
  • findings
    • typically a focal nodule with early enhancement (in the arterial phase) and rapid contrast washout (in the portal venous phase)
• Multi-phase contrasted MRI abdomen
  • indication
    • a confirmatory imaging study
  • findings
• enhancement in the arterial phase with rapid contrast washout

Studies

• Serum labs
  • α-fetoprotein (AFP) 
    • if elevated > 400-500 ng/mL
      • may be suggestive of HCC
      • may be seen in patients with active liver disease (e.g., HCV or HBV infection)
• a normal value does not exclude HCC

Differential

• Hepatic adenoma
  • differentiating factor
• benign liver tumor seen in patients with prolonged contraception use, anabolic steroid use, glycogen storage disorders, and pregnancy

Treatment

• Surgical
  • resection
    • indication
      • recommended if the lesion is resectable and the patient has good performance status
  • liver transplantation
    • indication
      • recommended based on the patient’s performance status and that the tumor is unresectable
  • liver-directed therapies
    • indication
      • in patients with local disease who are not candidates for resection or liver transplantation
        • may potentially down-stage the tumor, enabling the possibility of transplantation or resection
    • modalities
      • radioablation
        • delivers local radiofrequency thermal energy
      • transarterial chemoembolization (TACE)
        • delivers high-dose chemotherapy (e.g., cisplatin and doxorubicin) to local areas in the liver 
• therefore, this decreases the risk of developing systemic toxicities

Complications

• Hepatic failure
• Hemoperitoneum
• Portal, hepatic, or renal vein thrombosis