title: Iron overload in nonalcoholic steatohepatitis.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a major causative agent of chronic liver disease worldwide, but the actual mechanisms responsible for liver injury remain unclear. NAFLD includes a spectrum of clinical entities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with possible evolution to cirrhosis and hepatocellular carcinoma. Iron is considered a putative element that interacts with oxygen radicals in inducing liver damage/fibrosis and insulin resistance. The role of hepatic iron in the progression of NASH remains controversial, but in some patients, iron may have a role in the pathogenesis of NASH. Though genetic factors, insulin resistance, dysregulation of iron-regulatory molecules, erythrophagocytosis by Kupffer cells may be responsible for hepatic iron accumulation in NASH, exact mechanisms involved in iron overload remain to be clarified. Iron reduction therapy such as phlebotomy or iron-restricted diet may be promising in patients with NAFLD/NASH to reduce hepatic injury as well as insulin resistance. Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of phlebotomy and/or iron-restricted diet in NAFLD/NASH.
authors: Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, Mie, Japan. nfujita@clin.medic.mie-u.ac.jp
authors: Naoki
authors: N
authors: Fujita
authors: Yoshiyuki
authors: Y
authors: Takei
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002986:Clinical Trials as Topic; D018450:Disease Progression; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007333:Insulin Resistance; D019190:Iron Overload / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D019266:Iron, Dietary / Q000009:adverse effects / Q000378:metabolism*; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D018962:Phlebotomy
chemical_list: D019266:Iron, Dietary