Liver disease

Iron and the liver

The liver is the major site of iron storage in the body, and iron overload can cause hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. (Table 5.1) In hereditary hemochromatosis, a pathologic expansion of body iron stores can occur due to excessive absorption of dietary iron (Chapters 2,8). The excess iron is preferentially deposited in parenchymal cells of the liver and other organs. When storage mechanisms are overwhelmed, iron in low-molecular weight forms can catalyze free radical reactions (Chapter 3). The resulting oxyradicals have the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates, resulting in wide-ranging impairment in hepatocyte function and integrity (Chapter 3). Damage can result in increased hepatic fibrogenesis, micronodular cirrhosis, and hepatocellular carcinoma. Important co-factors of iron-induced liver injury include chronic hepatitis C, excess alcohol consumption, and steatosis. Liver fibrogenesis shows a concordance with hepatic iron concentration and the duration of exposure to high iron levels. Phlebotomy therapy can reverse iron-induced hepatic fibrosis, but cirrhosis is less amenable to phlebotomy treatment.

In disorders of erythropoiesis, increased iron absorption and tissue iron deposition can occur. (Chapters 21–25). A common factor in iron-loading anemias is refractory anemia with a hypercellular bone marrow and ineffective erythropoiesis. These conditions include β-thalassemia, sideroblastic anemias, congenital dyserythropoietic anemias, and pyruvate kinase deficiency. In these syndromes, clinical and pathologic consequences similar to those seen in HFE hemochromatosis can occur.