Histologic Features of the Liver in Insulin Resistance–Associated Iron Overload

Abstract

The aim of the present study was to describe histologic features of the liver in insulin resistance-associated hepatic iron overload (IR-HIO), defined as the association of metabolic disorders and hepatic iron overload. We included 139 patients in the study on the basis of one or more metabolic disorders and liver iron overload unrelated to usual causes. Liver biopsy specimens were reviewed, and histologic data were compared with those of a previously published, well-defined population with genetic hemochromatosis. Iron overload was characterized by a mixed pattern with iron deposits in hepatocytes and sinusoidal cells. Steatosis was present in 59.7% of patients with inflammation in 32.4% of cases. Periportal fibrosis was found in 67.4% of patients. These patients were older, had higher sinusoidal iron scores, and had a higher prevalence of steatosis and inflammation than patients without fibrosis. Iron overload in IR-HIO was histologically different from that in genetic hemochromatosis.

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

“…The association of insulin resistance with iron overload is largely based on studies of subjects with beta thalassaemia, transfusion iron overload, coexistent liver disease or idiopathic hyperferritinaemia [11,12,40,45,46]. The different distributions of iron in these conditions compared with haemochromatosis (reticuloendothelial vs hepatocellular) [1,47] may explain the differing phenotypes. The studies that have implicated insulin resistance specifically in hereditary haemochromatosis have studied subjects with established diabetes [10,48] and hyperglycaemia is by itself a major determinant of Si [13].…”

α1-Antitrypsin mutations in NAFLD: High prevalence and association with altered iron metabolism but not with liver damage

“…It is possible that the coexistence of multiple genetic abnormalities contribute to this atypical pattern of iron overload, [6][7][8][9] and it could be speculated that AAT affects the susceptibility to develop biochemical abnormalities related to NAFLD by altering iron metabolism, redox status and possibly cytokine profile. 36 AAT is not in linkage with any gene known to regulate iron metabolism, but AAT has been demonstrated to interact with TfR inducing ferritin synthesis.…”

“…[1][2][3] Diabetes, obesity, and dyslipidemia are the main risk factors for NAFLD, with insulin resistance as the key pathogenic event. 4,5 Hyperferritinemia associated with nonparenchymal iron overload in the presence of nearly normal transferrin saturation [6][7][8] represents a common clinical presentation of NAFLD, involving up to one third of unselected cases, 9 shares clinical features with the insulin resistance-hepatic iron overload syndrome (IR-HIO), 6 and is related to mutations in the HFE gene responsible for hereditary hemochromatosis (HHC) only in a minority of cases. [9][10][11] Although increased oxidative stress is possibly implicated, 12 the reasons why only a subset of subjects with metabolic liver disease shows alterations in iron parameters is at present unclear, but hyperferritinemia has bee reported to represent a risk factor for steatohepatitis and fibrosis.…”

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

“…The dysmetabolic iron overload syndrome (DIOS) commonly refers to the characteristic association of fatty liver with moderate histological iron deposition (hemosiderosis) and increased serum ferritin [17,20] .…”