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Hepatocellular Carcinoma (HCC)

BSG Guidelines for the management of hepatocellular carcinoma (HCC) in adults. Published: Apr 2024.

Definition

HCC is the most common form of primary liver cancer that originates from the hepatocytes.

Epidiemoilogy

Men are 3-5 times more likely to develop HCC than women, regardless of the underlying cause of liver disease

Incidence rises steeply from 40 y/o, peaking in those >80 y/o

In the UK, incidence rates are higher in Asian and Black ethnic groups

Aetiology

90% of cases occur in the context of chronic liver disease with cirrhosis from any cause being the strongest risk factor

Major specific risk factors:

  • Chronic Hepatitis B and C (accounts for >80% of HCC cases)
    • Hepatitis C is most common in the Western world
    • Hepatitis B is the leading cause in Asia and Africa, notably it could induce cancer even in the absence of cirrhosis by integrating into the host genome
  • Alcohol-related liver disease
  • MASLD

Clinical Features

HCC is often asymptomatic in early stages, and is often diagnosed incidentally via surveillance (ultrasound +/- AFP) in those with cirrhosis.

If symptomatic:

Tumour effect
  • RUQ pain / discomfort
  • Hepatomegaly with irregular / nodular liver edge
  • Early satiety (mass effect)
Decompensation of underlying cirrhosis
  • Jaundice
  • Ascites
  • Encephalopathy

HCC is highly vascular and can directly invade the portal vein, causing portal vein thrombosis, which worsens portal hypertension

Constitutional symptoms
  • Weight loss
  • Anorexia
  • Fatigue
  • Malaise

Investigation and Diagnosis

Approach:

  • HCC is often detected initially via surveillance (6-monthly liver ultrasound and AFP measurement) in high-risk patients (cirrhosis and certain hepatitis B patients)
  • Suspected HCC in patients with cirrhosis can be confirmed with radiological criteria alone (without the need for biopsy)
  • Biopsy (pathological diagnosis) is necessary in 1) inconclusive radiological findings or 2) patients without cirrhosis

Imaging

Screening imaging modality: liver ultrasound

  • If the lesion is >1 cm → refer for further imaging
  • If the lesion is <1 cm → repeat ultrasound in 3 months (as the diagnostic yield with cross-sectional imaging in small lesions is low)

Imaging of choice: multiphasic CT or MRI

Diagnostic criteria (specialist-level, but included for completeness):

  • For nodules ≥1 cm in a cirrhotic liver, HCC can be diagnosed if imaging shows:
    • Arterial phase hyperenhancement (lesion appears very bright / vascular)
    • Washout in portal venous / delayed phases (lesion appears darker / less vascular)

Biopsy

Typical biopsy findings:

  • Increased cell density
  • Loss of the reticulin framework

Management

Key management principles:

HCC stage Management approach Key management principles
Localised (very early / early) Curative intent
  • Surgical resection – preferred if there is preserved liver function and no portal hypertension
  • Liver transplantation – preferred if there is decompensated cirrhosis with Milan/UK criteria
  • Thermal ablation – for patients who are unsuitable for surgery
Locally advanced Loco-regional control Standard of care: TACE / TAE

Alternative:

  • Selective internal radiation therapy
  • Stereotactic radiotherapy
Advanced and metastatic Systemic therapy
  • 1st line: atezolizumab + bevacizumab
    • Oral alternative: srafenib / lenvatinib
  • 2nd line: tyrosine kinase inhibitors (e.g. sorafenib, lenvatinib, cabozatinib)

References

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