Primary hepatocellular carcinoma - Tumours of the liver

Primary hepatocellular carcinoma

Definition

Also called hepatoma, this is a tumour of the liver parenchyma.

Incidence/prevalence

Relatively uncommon in the Western world (2–3%), but by far the most common primary tumour of the liver worldwide.

Age

Usually in middle-aged and elderly.

Sex

M > F (3–4:1)

Geography

High incidence (40% of all cancers) in countries where predisposing factors such as hepatitis B are common, e.g. in Africa and the Far East.

Aetiology

Tumours arise in a chronically damaged liver especially in cirrhosis independent of the cause. Hepatitis B virus carrier states and chronic active hepatitis predisposes to primary hepatocellular carcinoma, especially when hepatitis B infection occurs in early life. Hepatotoxins such as mycotoxins present in food, increase the incidence of primary cancer. Aflatoxin, produced by Aspergillus flavus, is frequently found in stored nuts and grains in tropical countries. Other risk factors include drugs such as oral contraceptives following long-term use and androgens.

Pathophysiology

Tumour growth causes further impairment of liver function in already cirrhotic patients. Sometimes rare syndromes occur such as hypercalcaemia, hypoglycaemia and porphyria cutanea tarda (bullae on the skin following sun exposure or minor trauma due to a defect in a hepatic enzyme).

The tumour marker alpha-fetoprotein (αFP) is normally synthesised by the fetal liver, but in adults is present at very low levels (<10 ng/mL). When the tumour secretes αFP, as it does in most cases, it can reach very high levels. It is also raised in germ cell tumours (testicular and ovarian carcinoma).

Clinical features

Insidious onset with anorexia, weight loss and poorly localised upper right quadrant abdominal pain. On examination, the liver is usually enlarged and there may be an arterial bruit.

Macroscopy/microscopy

The right lobe is more frequently affected than the left. There is usually one large, haemorrhagic, soft mass or multifocal nodules. Sometimes the tumour is diffusely infiltrating with invasion of veins. Histologically cells range from well differentiated to anaplastic, with atypical nuclear cytology and abnormal architecture.

Complications

Metastases most commonly occur via the bloodstream to the lungs. Direct spread may also occur to abdominal lymph nodes and to other abdominal organs.

Investigations

Persistently high levels of serum α fetoprotein is very suspicious of carcinoma.

Ultrasound and CT abdomen are used to image tumours.

Definitive diagnosis is by liver biopsy.

Management

Curative treatment by partial liver resection is feasible in patients with tumour in only one lobe and with sufficient liver functional reserve, i.e. no cirrhosis.

Palliative treatment: Analgesia, arterial embolisation or percutaneous injection of alcohol may also cause tumour reduction and pain relief.

Prognosis

Primary hepatocellular tumour is a rapidly growing tumour, which usually presents late in patients who already have a serious underlying pathology, cirrhosis. The prognosis is very poor. Median survival is <6 months from diagnosis.