Dysregulation of iron and copper homeostasis innonalcoholic fatty liver

Elevated iron stores as indicated by hyperferritinemiawith normal or mildly elevated transferrin saturationand mostly mild hepatic iron deposition are acharacteristic finding in subjects with non-alcoholicfatty liver disease （NAFLD）. Excess iron is observedin approximately one third of NAFLD patients andis commonly referred to as the ＂dysmetabolic ironoverload syndrome＂. Clinical evidence suggests thatelevated body iron stores aggravate the clinical courseof NAFLD with regard to liver-related and extrahepaticdisease complications which relates to the fact thatexcess iron catalyses the formation of toxic hydroxylradicalssubsequently resulting in cellular damage. Ironremoval improves insulin sensitivity, delays the onsetof type 2 diabetes mellitus, improves pathologic liverfunction tests and likewise ameliorates NAFLD histology.Several mechanisms contribute to pathologic ironaccumulation in NAFLD. These include impaired ironexport from hepatocytes and mesenchymal Kupffer cellsas a consequence of imbalances in the concentrationsof iron regulatory factors, such as hepcidin, cytokines,copper or other dietary factors. This review summarizesthe knowledge about iron homeostasis in NAFLD andthe rationale for its therapeutic implications.