Hepatocelular Carcinoma (HCC)

Risk Factors:

• Cirrhosis of any cause (viral, alcoholic, metabolic, autoimmune, genetic etiologies)

  • Cirrhosis present in over 80% of HCC cases

• Chronic HBV and HCV infection (with or without cirrhosis, especially with high viral load or active replication)

  
  

Screening:

• At-risk populations requiring screening:

  • Child-Pugh Class A or B cirrhosis of any etiology

  • Child-Pugh Class C cirrhosis patients who are transplant candidates

  • Hepatitis B carriers without cirrhosis

• Screening using ultrasound and AFP every 6 months.

  • If a nodule ≥1 cm or rising AFP is detected → CT or MRI are indicated

Diagnosis:

• AFP alone lacks sufficient specificity and sensitivity for HCC diagnosis

• Calculate Child-Pugh for all cirrhotic patients

• Imaging:

  • CT multiphase shows “Hyperenhancement on arterial phase, delayed washout”

  • Diagnostic imaging criteria apply only to high-risk patients (Cirrhosis, Chronic hep B, current/prior HCC)

• Liver biopsy:

  • Indications:

    • Non-cirrhotic patients (imaging alone is insufficient)

    • Cirrhotic patients with inconclusive imaging/ if lesion does not meet criteria for definite HCC (LI-RADS 5)

  • Biopsy is generally not indicated for a patient with cirrhosis who has a liver mass if the lesion meets established imaging criteria for HCC on CT or MRI.

• Paraneoplastic hypoglycemia, hyperlipidemia, hypercalcemia, erythrocytosis is possible

BCLC (Barcelona Clinic Liver Cancer) staging system:

• Integrating criteria:

  • Tumor burden

  • Patient performance status (PS)

  • Liver function (bilirubin and portal pressure)

• Stages:

  • 0 (very early):

    • 1 nodule ≤2 cm, PS 0, preserved liver function

  • A (early):

    • 1-3 nodules each ≤3 cm, PS 0, preserved liver function

  • B (intermediate):

    • Multinodular, PS 0, preserved liver function

  • C (advanced):

    • Portal vein invasion/ extrahepatic spread, PS 1-2, preserved liver function

  • D (terminal):

    • Any tumor burden, PS 3-4, end-stage liver function

Treatment:

BCLC stage A or B:

• Resection:

  • If solitary lesion with preserved liver function + appropriate Future liver remnant (FLR)

    • FLR: To determine surgical candidacy and preventing post-hepatectomy liver failure

    • Required FLR volume is based on underlying liver parenchymal status:

      • Non-cirrhotic liver: ≥20% of liver volume

      • Cirrhotic liver (Class A) and Chemotherapy-exposed liver: ≥30% of liver volume

  • No adjuvant treatment

    • Post-op observation is preferred (though high recurrence risk)

  • Treat Hep B or C if present

• Transplant:

  • MILAN Criteria:

    • Patient is eligible for liver transplant if they have either:

      • one HCC lesion ≤5 cm

      • 1-3 HCC lesions each ≤3 cm

      • No evidence of vascular invasion/ extrahepatic disease

  • Contraindicated in portal vein thrombosis

• Radiofrequency Ablation (RFA):

  • For small (≤3 cm) and accessible lesions in patients with adequate liver function who are not surgical or transplant candidates

• Transarterial radioembolization (TARE), Transarterial chemoembolization (TACE):

  • For large lesion (>4cm) with no extrahepatic disease/ vascular invasion

  • Relative contraindications:

    • Child-Pugh Class C

    • Portal vein thrombosis

    • Bilirubin >3

  • TARE is beneficial in patients with solitary HCC <8 cm (LEGACY)

BCLC stage C:

• First line:

  • Atezolizumab + Bevacizumab (IMBrave-150)

    • Needs EGD to rule out esophageal varices prior to starting

  • Durvalumab + Tremelimumab-actl (HIMALAYA)

    • Does not need EGD prior to starting

  • Durvalumab

  • Lenvatinib

  • Sorafenib

  • Tislelizumab

  • Nivolumab + Ipilimumab

• Subsequent line (if disease progression):

  • Cabozantinib (CELESTIAL)

  • Regorafenib (RESOURCE)

  • Ramucirumab (REACH-2): Consider in patients with AFP>400

• If NTRK gene fusion positive:

  • Entrectinib

  • Larotrectinib

  • Repotrectinib

BCLC stage D:

• Hospice/ supportive care

• Systemic therapy is generally indicated for patients with Child-Pugh Class A or ≤B7

  • Not recommended for Child-Pugh Class >B7 or C