Hepatic Cancer

Introduction

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, originating from hepatocytes. It accounts for approximately 90% of all primary liver cancers and typically arises in the setting of chronic liver disease, particularly cirrhosis and chronic viral hepatitis (HBV and HCV).

Peak Incidence

• Most common between the ages of 70 and 75.
• Higher prevalence in individuals with cirrhosis, particularly due to hepatitis B, hepatitis C, alcohol misuse, or non-alcoholic fatty liver disease.

Pathophysiology

• Chronic liver injury leads to cycles of hepatocyte regeneration and mutation, promoting malignant transformation.
• Cirrhosis is present in over 80% of cases.
• Hepatitis B virus can directly cause HCC, even in the absence of cirrhosis.

Symptoms

Early Stage

• Often asymptomatic
• Symptoms are usually non-specific and may relate to underlying cirrhosis

Advanced Stage

• Weight loss
• Anorexia
• Right upper quadrant pain or discomfort
• Jaundice
• Ascites

Signs

• Jaundice
• Ascites – Due to portal hypertension or liver failure
• Hepatomegaly – May be nodular or tender
• Right upper quadrant tenderness on palpation

Diagnosis

Laboratory Investigations

• Full blood count (FBC) – May reveal thrombocytopenia or polycythaemia
• Liver function tests (LFTs):
  • Elevated ALT/AST – Suggest hepatocellular damage
  • Elevated bilirubin – Indicates impaired excretion
  • Low albumin, prolonged prothrombin time – Reflect impaired synthetic function
• Coagulation profile – To assess clotting status
• Alpha-fetoprotein (AFP):
  • May be elevated in HCC, but not specific or diagnostic alone

Imaging

• Abdominal ultrasound – First-line in at-risk populations (e.g. patients with cirrhosis)
• Multiphase contrast-enhanced CT or MRI – Diagnostic imaging of choice for characterisation
  • HCC typically shows arterial enhancement with venous phase washout
• Liver biopsy – Reserved for cases where imaging is inconclusive or diagnosis is uncertain, especially in non-cirrhotic patients

Complications

• Portal vein thrombosis – Common in advanced disease
• Metastasis – Typically to lungs, bone, or lymph nodes in late stages
• Budd–Chiari syndrome – Obstruction of hepatic veins
• Hepatic failure – Due to progressive tumour burden on functional liver parenchyma
• Tumour rupture – Can cause life-threatening haemoperitoneum
• Paraneoplastic syndromes, including:
  • Hypoglycaemia (from insulin-like growth factor production)
  • Polycythaemia (from erythropoietin production)
  • Hypercalcaemia (from parathyroid hormone-related peptide secretion)

Management

Curative (Early-stage disease)

• Surgical resection – In patients with preserved liver function and without significant portal hypertension
• Liver transplantation – In suitable candidates meeting Milan criteria (e.g. single tumour ≤5 cm, or up to 3 tumours each ≤3 cm, without vascular invasion or extrahepatic spread)
• Local ablative therapy – e.g. radiofrequency ablation (RFA) or microwave ablation, typically used for small tumours (<3 cm)

Non-curative (Advanced-stage disease)

• Targeted therapy – e.g. sorafenib or lenvatinib
• Systemic chemotherapy – Limited benefit; not first-line
• Palliative care – Focus on symptom control, quality of life, and end-of-life planning

Management of Underlying Liver Disease

• Antiviral therapy – For chronic hepatitis B or C

• Lifestyle modification – Alcohol abstinence, weight loss in NAFLD, and avoidance of hepatotoxic medications