Hepatocellular Carcinoma

Definition

• The most common primary liver cancer (≈75–85% of cases).
• Typically arises in the setting of chronic liver disease and cirrhosis.

Risk Factors

• Chronic viral hepatitis (HBV, HCV).
• Alcohol-related liver disease.
• Non-alcoholic fatty liver disease (NAFLD/NASH).
• Aflatoxin B1 exposure (contaminated food, endemic in some regions).
• Genetic/metabolic disorders (e.g., hemochromatosis, α1-antitrypsin deficiency, Wilson’s disease).

Clinical Presentation

• Often asymptomatic early (detected on surveillance in cirrhotic patients).
• Symptoms: weight loss, fatigue, RUQ pain, hepatomegaly, jaundice, ascites.

Diagnosis

• Imaging: Multiphasic CT or MRI (arterial enhancement + venous washout = diagnostic).
• Serum AFP (alpha-fetoprotein): may be elevated, but not always (limited sensitivity/specificity).
• Biopsy: not always needed if imaging is characteristic.

Staging / Prognosis

• Commonly staged by BCLC (Barcelona Clinic Liver Cancer) system:
  • Considers tumor burden, liver function (Child-Pugh), and performance status.

Treatment (pharmacist-relevant)

• Curative (early-stage, preserved liver function):
  • Surgery (resection)
  • Liver transplantation (especially if within Milan criteria)
  • Ablation (radiofrequency, microwave)
• Locoregional (intermediate stage):
  • TACE (Transarterial chemoembolization)
• Systemic therapy (advanced/unresectable):
  • First-line:
    • Atezolizumab + Bevacizumab (preferred standard now, IMbrave150 trial)
    • Alternatives: Durvalumab ± Tremelimumab, Lenvatinib, Sorafenib
  • Second-line:
    • TKIs: Regorafenib, Cabozantinib
    • Immunotherapy: Nivolumab, Pembrolizumab (selected patients)
    • Ramucirumab (if AFP ≥ 400 ng/mL)

Pharmacist Considerations

• Monitor liver function (many drugs require dose adjustments in hepatic impairment).
• TKIs (Sorafenib, Lenvatinib, Regorafenib, Cabozantinib):
  • Toxicities: hand-foot syndrome, diarrhea, hypertension, hepatotoxicity.
• Immunotherapy (PD-1/PD-L1 inhibitors):
  • Immune-related adverse events (hepatitis, colitis, endocrinopathies).
• Bevacizumab: monitor for bleeding, hypertension, proteinuria.
• Drug interactions: CYP3A4 metabolism for many TKIs.
• Surveillance: AFP and imaging used to monitor response/recurrence.

Summary:

HCC is the most common primary liver cancer, usually arising from chronic liver disease. Curative options (surgery, transplant, ablation) are limited to early-stage disease; otherwise, treatment includes TACE or systemic therapy (atezolizumab + bevacizumab, TKIs, immunotherapy). Pharmacists play a key role in managing hepatic dosing, drug interactions, and toxicity monitoring