Premalignant lesions and hepatocellular carcinoma in a non-cirrhotic alcoholic patient with iron overload and normal transferrin saturation

A 66-year-old white man had a hepatic resection for a 6-cm well-differentia ted hepatocellular carcinoma which had developed in a non-cirrhotic liver. The only risk factors found were heavy drinking, smoking and heterozygosity for the C282Y mutation of the HFE gene, The liver was mildly fibrotic and overloaded with iron. It also contained numerous iron-free hepatocellular l esions from <1 to 10 mm, suggesting a premalignant change. These lesions we re of three types: (i) iron-free foci, (ii) hyperplastic nodules and (iii) dysplastic nodules with severe dysplasia or even foci of well-differentiate d grade I hepatocellular carcinoma. This observation suggests the possibili ty of malignant transformation of the liver in the newly-described syndrome of iron overload and normal transferrin saturation. It also illustrates th e multistep process of carcinogenesis in the non-cirrhotic liver.