Introduction

Due to its direct connections to the intestinal tract, the liver is the first target organ of hemochromatosis. In this respect, it plays a key role in accumulating iron absorbed by the intestine. This storage function has two main consequences: first, it exerts a relative protective effect over other organs second, longstanding and massive iron excess can induce damage of the liver that may lead to the development of fibrosis, cirrhosis, and hepatocellular carcinoma. The clinical spectrum of hepatic disease in hemochromatosis is therefore particularly broad, ranging from silence to extreme severity. In addition, this expression can be modulated by various coexisting factors and coincidental hepatic disorders. The diagnosis of hepatic disease in persons with hemochromatosis needs a careful differential approach due to the characteristics of newly described hepatic iron overload syndromes. Finally, the response of these hepatic disorders to treatment (i.e., therapeutic phlebotomy) depends on the stage of hepatic damage.

The clinical expression of the hemochromatosis liver

The ‘silent’ liver

Today, this is often the status of the liver in persons with hemochromatosis. In most patients, particularly those <30 years of age, the liver is clinically silent. The clinical examination is negative, there is no detectable hepatomegaly, and hepatic function tests are normal. At this stage, the diagnosis of hepatic iron overload can only be made by magnetic resonance imaging (MRI) and hepatic biopsy. However, performing a hepatic biopsy in the absence of either clinical or biochemical signs suggestive of hepatic disease is becoming less usual in patients suspected of having hemochromatosis, and is reserved for patients in whom the diagnosis of hemochromatosis cannot be established by the detection of homozygosity for the HFE mutation C282Y.