| [ Summary ] |
Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) have been described as being associated with hyperferritinemia and hepatic iron overload. Hepatic iron deposition is believed to be involved in the development of NASH, since excessive hepatic iron produces reactive oxygen species which exacerbate liver injury. In addition, the pattern of hepatic iron deposition plays a role in disease development. However, whether parenchymal iron deposition or non-parenchymal iron deposition contributes to progressive liver injury remains to be determined. The mechanisms underlying hepatic iron overload in NAFLD have not been elucidated. Mutations of the hemochromatosis gene (C282Y and H63D) and insulin resistance have been connected to disturbances in iron metabolism. It is known that mammalian iron homeostasis is regulated by hepcidin. Hepcidin, which is exclusively synthesized by hepatocytes, causes internalization and degradation of the iron-transporter ferroportin on duodenal enterocytes and macrophages, thereby blocking iron absorption and iron recycling. The negative feedback system for hepcidin production, to mitigate iron overload, may be impaired in NAFLD, cases leading to iron dysmetabolism and hepatic iron overload. Iron removal therapy may improve not only liver function but also insulin resistance in patients with NASH. |