Clinical Review

Hepatocellular carcinoma for the non-specialist

BMJ 2009; 339 doi: (Published 04 December 2009) Cite this as: BMJ 2009;339:b5039
  1. T Kumagi, lecturer 1,
  2. Y Hiasa, lecturer1,
  3. G M Hirschfield, assistant professor of medicine2
  1. 1Gastroenterology and Metabology, Ehime University, School of Medicine, Ehime, 791-0295, Japan
  2. 2Liver Centre, Toronto Western Hospital, Toronto, M5T 2S8, Canada
  1. Correspondence to: G M Hirschfield, Toronto Western Hospital, Toronto, ON, M5T 2S8, Canada gideon.hirschfield{at}

Summary points

  • Hepatocellular carcinoma is a leading cause of death worldwide, and cirrhosis is the main risk factor

  • Infection with hepatitis B and hepatitis C is the main cause of underlying liver disease

  • Prevention of chronic liver disease would greatly reduce incidence

  • Early tumour diagnosis through screening of at risk groups is cost effective

  • New treatments, such as sorafenib, are exciting potential adjuncts to patient care

Hepatocellular carcinoma is the third most common cause of cancer related mortality worldwide, and in the United Kingdom population data show that age standardised incidence rose from 1.4 to 3.9 per 100 000 people between 1975 and 2006 ( Cirrhosis of the liver is the strongest predisposing factor—80-90% of cases arise from chronic liver disease. Furthermore, in cohort studies of patients with cirrhosis, hepatocellular carcinoma is the leading cause of liver related death.1 2

Sources and selection criteria

We based this review on the available evidence presented in international consensus guidelines and cited in PubMed after searching with the terms “hepatocellular carcinoma”, “natural history”, “surveillance”, “screening”, “outcome”, “treatment”, and “prevention”.

What predisposes people to hepatocellular carcinoma?

Worldwide rates of hepatocellular carcinoma (fig 1) correlate with widespread infection with hepatitis B in Asia and Africa and hepatitis C in Western countries and Japan. These viral infections are the most common underlying causes of liver disease that predispose to hepatocellular carcinoma (box 1).

Box 1 Important risk factors for hepatocellular carcinoma

  • Cirrhosis (any cause)

  • Chronic hepatitis B and C infection

  • Sustained added excess alcohol consumption

  • Non-alcoholic steatohepatitis (both independently and as a cofactor)

  • Diabetes

  • Aflatoxin exposure

  • Older age

  • Male sex

  • Family history of hepatocellular carcinoma

Fig 1 2002 estimates of age standardised incidence of hepatocellular carcinoma. Incidence varies 14-fold across the world for men and 10-fold for women. The disease is still rare in the UK—140th of the 172 countries worldwide for men and 136th for women. Adapted, with permission, from Cancer Research UK

Chronic …

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