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End-stage cirrhosis in the absence of hereditary hemochromatosis (HHC) can be associated with moderate to marked hepatic iron overload, especially in liver disease as a result of alcohol and/or hepatitis C. However, no published studies have addressed extrahepatic iron deposition in this setting.A retrospective case series from three autopsied patients who died from end-stage cirrhosis associated with significant hepatic iron overload. Histology of vital organs was performed to detect extrahepatic iron deposition. HFE genotyping for the C282Y and H63D mutations was determined from archival tissue. Hepatic iron index and hepatic iron concentration (HIC) were quantified from formalin-fixed, paraffin-embedded tissue. Medical records were reviewed for possible causes of iron overload.Two patients were H63D heterozygous (H63D +/−) and one was wild type (C282Y −/−, H63D −/−). Histology revealed evidence of stainable iron in the heart and pancreas of all three subjects. Additionally, stainable iron was seen in the stomach in one subject and in the thyroid, pituitary, choroid plexus and testes in another subject. HIC ranged from 4354 to 6834 μg/g dry weight and HII from 1.8 to 2.2 (μmol/g/years).Iron overload secondary to end-stage liver disease can be associated with iron deposition in other organs in the absence of HFE-1 HHC.