Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and due to the high endemic rates of hepatitis B infections constitutes approximately 5.4% of all cancers ¹. 

Demographics and clinical presentation

The demographics are strongly influenced by the regions in which hepatitis B chronic infection are common, which account for over 80% of cases world wide. The highest prevalence is in Asia.

In western countries the rate is lower and alcohol accounts for a greater proportion of cases.

Risk factors include ¹:

• hepatitis B (HBV) infection: 10% 5 year cumulative risk ⁵
• hepatitis C (HCV) infection: 30% 5 year cumulative risk
• alcoholism: 8% 5 year cumulative risk
• biliary cirrhosis: 5% 5 year cumulative risk
• food toxins e.g. aflatoxins
• congenital biliary atresia
• inborn errors of metabolism
  • haemochromatosis: 21% 5 year cumulative risk
    
  • Alpha-1 antitrypsin deficiency
  • Type 1 Glycogen storage disorder
  • Wilson disease

HCC are typically diagnosed in adults, of late middle age or elderly. The tumour is however also identified in the paediatric population where it is the second most common primary liver tumour after hepatoblastomas.

Presentation is variable, and in affluent nations is often found in the setting of screening programs for patients with known risk factors. Otherwise presentation may include:

• constitutional symptoms
• jaundice
• portal hypertension from invasion of the portal vein
• hepatomegally / mass

alpha-fetoprotein levels are elevated in 50-75% of cases 

Pathology

The origin of HCCs is believed to relate to repeated cycles of necrosis and regeneration, irrespective of cause. In addition the HBV and HCV genome contains genetic material that may predispose cells to accumulate mutations, or disrupts growth control, thus allowing for a second mechanism by which infection with these agents predisposes to HCC ¹

Typically HCCs appear pale masses within the liver, and may be unifocal, multifocal or diffusely infiltrative at the time of presentation. Microscopically they range from well differentiated to undifferentiated .

Metastases are most commonly to lung, adrenal glands, lymph nodes, and bone.

Fibrolamellar hepatocellular carcinoma is distinct variant with different demographics and risk factors.

Radiographic features

HCC can have a variety of appearances:

• focal (massive)
• multifocal (nodular)
• diffuse

They receive most of their blood supply from the hepatic artery accounting for its characteristic enhancement pattern: early arterial enhancement with early washout. 

Additionally these tumours have a propensity to invade vascular structures, most commonly the portal vein, but also the hepatic veins. One should remember that a large number of patients will have concomitant cirrhosis, and thus be at risk for bland portal vein thrombosis also.

CT

• focal HCC
  • large usually hypodense mass
  • may have necrosis / fat / calcification
• multifocal HCC
  • multiple masses of variable attenuation lesions
  • may also have central hypodense necrotic portions
• diffuse HCC
  • may be difficult to distinguish from associated cirrhosis

Enhancement pattern is the key to correct assessment of HCCs. Usually the mass enhances vividly during early arterial (~25 seconds) and then washes out, becoming indistinct or hypodense compared to the rest of the liver at the portal phase. 

Additionally them may be associated with a wedge shaped perfusion abnormality due to arterioportal shunts (APS), and this in turn can result in focal fatty change in the normal liver or focal fatty sparing in the diffusely fatty liver ⁷. A halo of focal fatty sparing may also be seen around an HCC in an otherwise fatty liver ⁶.

Portal vein tumour thrombus can be distinguished from bland thrombus by demonstrating enhancement.

Ultrasound

Variable appearance depending on individual lesion, size, and background liver.

Typically a small focal HCC appears hypoechoic compared to normal liver. Larger lesions are heterogeneous due to fibrosis, fatty change, necrosis and calcification ⁸. Again a peripheral halo of hypoechogenicity may be seen with focal fatty sparing.

If diffuse it may be difficult to identify or distinguish from cirrhosis.

MRI

When seen in the setting of cirrhosis, small HCCs need to be distinguished from regenerative and dysplastic nodules (see cirrhosis article)

• T1  
  • variable
  • iso or hyperintense c.f. surrounding liver
  • hyperintensity may be due to
    • intratumoural fat ⁵
    • decreased intensity in surrounding liver
  • enhancement is usually arterial and may be brief
  • rapid wash out becoming hypointense c.f. remainder of the liver (96% specific) ⁵. This is on account of the supply to HCCs being from the hepatic artery rather than portal vein 
  • rim enhancement may persist (referred to as a capsule)
  • the larger the lesion the more heterogeneous the enhancement
• T2
  • variable
  • typically hyperintense
• Post SPIO (Iron oxide) – increases sensitivity in diagnosing small HCC’s

DSA

• Threads and Streaks’ pattern – sign of tumour thrombus in portal vein
• hypervascular tumour

Treatment and prognosis

If the lesion is small then resection is possible (partial hepatectomy) and may result in cure, as may liver transplantation with total hepatectomy. The remarkable ability of the liver to regenerate means that up to 2/3rds of the liver can be resected ¹⁰.

If this is not possible then a variety of options exist including chemotherapy, embolisation, chemoembolisation, and radiofrequency ablation.

If a tumour is resectable then 5 year survival is 37-56% ³.

Differential diagnosis

• hepatic metastases 
• focal nodular hyperplasia (FNH)
• hepatic adenoma
• THADs
• biliary papillomatosis

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