Premalignant lesions and hepatocellular carcinoma on non cirrhotic liver overloaded with iron

A 68-year old mildly obese Caucasian man underwent hepatic resection for multinodular hepatocellular carcinoma which had developed in the left lobe of non-cirrhotic liver. The only risk factors found were heavy drinking, smoking, and serum markers of hepatitis B virus without virus genome in hepatocytes. The non tumoral liver was mildly fibrotic and iron overloaded (hepatic iron index: 1.6) with three types of iron-free lesions: (i) periportal clear hepatocyte foci, (ii) hyperplastic nodules and (iii) dysplastic or neoplastic nodules with well to moderately-differentiated hepatocellular carcinoma. The genetic investigation was negative for the C282Y and the H63D mutations of the HFE gene. This observation illustrates the multistep process of carcinogenesis in the non-cirrhotic liver and raises the question of i) the origin of this iron overload possibly linked to insulin resistance syndrome and ii) the role of iron as a co-carcinogen.