2-5 Hepatic iron deposition in the setting of chronic liver disea

2-5 Hepatic iron deposition in the setting of chronic liver disease may be present in one of three different patterns: exclusively in hepatocytes, exclusively in cells of the reticuloendothelial system (RES), or in a mixed pattern involving both hepatocytes and RES.2-5 In hereditary hemochromatosis

types 1, 2, and 3, iron preferentially SAR245409 clinical trial accumulates in hepatocytes because of mutations in the hemochromatosis gene (HFE), the hemojuvelin (HJV) or hepcidin genes, and the transferrin receptor 2 (TFR2) gene, respectively.2-5 In contrast, hepatic iron deposition in the setting of cirrhosis and secondary iron overload occurs primarily in RES cells and usually begins with sinusoidal lining cells in an azonal pattern.2-5 Iron deposition in patients with alcoholic fatty liver disease, NAFLD, or a chronic hepatitis C infection may occur in any of these three patterns.2-5 The Dabrafenib contribution of hepatic iron accumulation to the severity or progression of chronic liver diseases other than hemochromatosis remains unclear. A number of studies have assessed the relationship

between hepatic iron loading and disease stage in chronic hepatitis C; the majority of these studies (but not all) support an association between advanced fibrosis and the presence of iron deposition in the nonparenchymal RES cells (i.e., sinusoidal, endothelial, and portal tracts).6, 7 In contrast, parenchymal iron deposition is a feature of alcoholic liver disease, although RES iron is more prevalent in the advanced stages of disease.8 NAFLD is the most common liver disease in the United States and may be present in up to 30% of the general population.9 A subset of patients SSR128129E with NAFLD have nonalcoholic steatohepatitis (NASH), a more severe form of this disease associated with hepatocellular (HC) injury,

inflammation, and varying levels of fibrosis. A number of previous studies have investigated the role of iron stores in NAFLD by assessing the presence of stainable hepatic iron deposits, the biochemical hepatic iron content, or both. However, the findings thus far have been conflicting, with some studies finding hepatic iron deposition to be associated with increased disease severity10-12 and others not finding such an association.13-16 One previous study examining the distribution of iron in 157 patients with NASH-related cirrhosis, including 51 with hepatocellular carcinoma (HCC), demonstrated that patients with HCC were more likely to have mild to moderate RES cell iron deposits than patients without HCC.

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