Genetic haemochromatosis constitutes a high risk factor for the development of hepatocellular carcinoma. It is widely accepted that venesection prevents the evolution of cirrhosis in haemochromatosis and indirectly protects against the development of hepatocellular carcinoma. Clinical, pathological and radiological data are presented on three patients who did not conform to the 'siderosis-cirrhosis-carcinoma' sequence and in whom prompt and adequate iron depletion did not prevent the development of cancer. This is the first report of hepatocellular carcinoma intervening in non-cirrhotic liver in two siblings with genetic haemochromatosis. The current literature on the subject is reviewed. The direct oncogenic role of iron remains to be elucidated. Hepatocellular carcinoma should be considered as a differential diagnosis in patients with non-cirrhotic genetic haemochromatosis who present with clinical deterioration during the course of an otherwise uneventful venesection programme.
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