There are several cofactors which affect body iron metabolism and accelerate iron overload.Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload.In these conditions,iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species(ROS)produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron.Furthermore, hepcidin,antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release.In patients with ceruloplasmin deficiency,anemia and secondary iron overload in liver and neurodegeneration are reported. Furthermore,there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states.Ineffective erythropoiesis is also an important factor to accelerate iron overload, which is associated with diseases such as thalassemia and myelodysplastic syndrome.When this condition persists,the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will thereafter occurs.In porphyria cutanea tarda,iron is secondarily accumulated in the liver. There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In these conditions, iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species (ROS) produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron. Fluorrthermore, hepcidin, antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release. In patients with ceruloplasmin deficiency, anemia and secondary iron overload in liver and neurodegeneration were reported..., there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states. Iffective erythropoiesis is also an important factor to accelerate iron overload, which is associated with diseases such as thalassemia and myelodysplastic synd this condition persists, the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will soon occur.In porphyria cutanea tarda, iron is secondarily accumulated in the liver.