Describe hepatocellular carcinoma with its aetiology, morphology and diagnosis.

Definition and Epidemiology

• Male to female ratio 3:1 to 8:1
• Highest incidence in sub-Saharan Africa and East Asia, where hepatitis B and aflatoxin exposure are common
• Arises on a background of cirrhosis in 80 to 90% — the great exception being hepatitis B, which can cause it without cirrhosis

Aetiology

Morphology

• Three macroscopic patterns — unifocal (a single large mass), multifocal (multiple nodules, the commonest in cirrhosis), and diffusely infiltrative (permeating the whole liver)
• Soft, often bile-stained green-yellow, with areas of haemorrhage and necrosis
• Strong tendency to invade veins — portal and hepatic vein invasion is characteristic and may extend into the inferior vena cava and right atrium
• Microscopy — cells resembling hepatocytes in trabecular, pseudoglandular or solid patterns; bile production by tumour cells is diagnostic; mallory bodies and fatty change may be present
• Fibrolamellar variant — young adults, NO cirrhosis, no viral association; a single large tumour of eosinophilic cells in lamellated fibrous bands; AFP usually normal; better prognosis and often resectable

Clinical Features and Diagnosis

• Often presents as decompensation of previously stable cirrhosis — new ascites, jaundice, encephalopathy or variceal bleeding
• Right upper quadrant pain, weight loss, a hard irregular enlarging liver, and sometimes a bruit over the tumour
• Blood-stained ascites; rupture with haemoperitoneum is a recognised presentation
• Paraneoplastic — polycythaemia (erythropoietin), hypoglycaemia (insulin-like growth factor), hypercalcaemia, hypercholesterolaemia
• Alpha-fetoprotein — raised in about 60 to 70%; also raised in pregnancy, germ cell tumours, cirrhosis and hepatitis, so it is not specific enough for diagnosis alone
• Triple-phase CT or MRI shows the characteristic pattern of arterial enhancement with venous washout, which in a cirrhotic liver is diagnostic without biopsy

Applied Aspects

• Six-monthly ultrasound surveillance in cirrhosis, with or without AFP, detects tumours while they are still curable — the single most useful measure
• Prevention is far more effective than treatment — universal hepatitis B vaccination has already reduced incidence measurably in vaccinated cohorts, and curing hepatitis C reduces risk substantially
• Reduce aflatoxin exposure by proper drying and storage of grain and groundnuts — simple, cheap and relevant in India
• Curative options — resection in good liver function, transplantation (which treats the cirrhosis as well), and ablation for small tumours; the Milan criteria guide transplant eligibility
• Palliative options — transarterial chemoembolisation, exploiting the tumour’s arterial supply while normal liver relies on the portal vein; and systemic agents such as sorafenib and immunotherapy
• Distinguish from metastases, which are far commoner in the liver than primary tumours — multiple lesions in a non-cirrhotic liver suggest a primary elsewhere, usually colorectal, and demand a search for it