Iron overload and cofactors with special reference to alcohol, hepatitis C virus infection and steatosis/insulin resistance

Table 1 Cofactors of iron overload

1 Alcohol (Alcoholic liver disease)

2 Infection (Hepatitis C virus infection, etc)

3 Obesity and insulin resistance (Nonalcoholic steatohepatitis)

4 Copper (Ceruloplasmin deficiency)

5 Porphyrin (Porphyria)

6 Ineffective erythropoiesis (Thalassemia, myelodysplastic syndrome)

7 Others

Table 2 Speculated effects of iron on HCV

1 Immunological modification (Immunological escape of HCV)

Decrease of Th1 activity

Impaired function of macrophage and Kupffer cells

Decrease of innate immunity (Natural resistance macrophage protein 2)

2 Increase of liver toxicity by iron-mediated radical formation

Reactive oxygen production through fenton reaction

Induction of apoptosis

Acceleration of fibrinogenesis

DNA damage and carcinogenesis

3 Effect on cell signalling

Decrease of interferon responsiveness by NFκB activation

4 HCV proliferation

Activation of translation initiation factor 3 (eIF3)

Suppression of HCV RNA polymerase (NS5B) activity