Utility of hepatic or total body iron burden in the assessment of advanced hepatic fibrosis in HFE hemochromatosis

Abstract

Development of advanced hepatic fibrosis in HFE Hemochromatosis (HH) is influenced by hepatic iron concentration (HIC) and age. In patients with HH, it is important to assess the likelihood of cirrhosis and thus the need for confirmatory liver biopsy. Therapeutic phlebotomy also provides an estimate of mobilisable iron stores. We determined whether mobilisable iron stores may predict the presence of advanced fibrosis. Retrospective analysis of 137 male and 65 female HH subjects was undertaken. Biochemical, histological and phlebotomy data were available on all subjects. The mean values of HIC, HIC × [age], mobilisable iron, mobilisable iron × [age] and serum ferritin in the cohort were higher in the group with advanced fibrosis. HIC had an optimum sensitivity and specificity of 73% for the diagnosis of advanced liver fibrosis, with a cut-off HIC level of 200 µmol/g (AUROC 0.83, p < 0.0001). AUROC for HIC was greater in females (0.93) than males (0.79). Mobilisable iron had an optimum sensitivity and specificity both of 83% at a cut-off of 9.6 g for the prediction of advanced fibrosis in all subjects (AUROC 0.92, p < 0.0001). Mobilisable iron stores provide a simple, clinically useful indication of the risk of advanced fibrosis and should routinely be considered.

Medical Case Report on Repeat Treatment of Restless Legs Syndrome with Intravenous Infusion of Iron

“…However, a serum ferritin exceeding 300 μg/L in a subject who had deliberate iron infusion would not trigger such an alert since the cause is known. Mild elevations below 1,000 μg/L are “tolerable” and in the absence of hereditary haemochromatosis, the risk of hepatic iron overload and liver toxicity is exceedingly low at this concentration [ 26 , 27 , 28 ]. Thus, referral to a gastroenterologist, haematologist or physician with an interest in iron overload is considered appropriate if serum ferritin is >1,000 μg/L or if the cause of elevated serum ferritin is unclear.…”

The ancestral haplotype markers HLA -A3 and B7 do not influence the likelihood of advanced hepatic fibrosis or cirrhosis in HFE hemochromatosis

“…Alcohol consumption was defined by the National Health and Medical Research Council of Australia as 1 standard drink containing 10 g of alcohol; safe recommended consumption levels being ≤ 210 g per week for males and ≤ 140 g per week for females. The hepatic iron concentration (HIC) was determined using atomic absorption spectrophotometry on fresh liver biopsy specimens 24 . Fibrosis staging was performed by liver histopathologists with expertise in HFE hemochromatosis using paraffin-embedded sections, stained with haematoxylin and eosin and Perls’ Prussian blue method.…”

Clinical practice guidelines on hemochromatosis: Asian Pacific Association for the Study of the Liver

“…Advanced liver fibrosis or cirrhosis [ 54 ] in HFE-related hemochromatosis is rare under the age of 45 years in the absence of other liver co-morbidities, occurring in 8–25% of all HFE p.Cys282Tyr homozygotes [ 38 , 51 , 52 , 55 , 56 ]. Risk factors include excessive alcohol consumption, diabetes mellitus, arthritis, serum ferritin levels greater than 1000 µg/L, liver iron concentration greater than 200 µmol/g, and total mobilizable iron stores by therapeutic phlebotomy of greater than 9.6 g [ 47 , 56 – 60 ].…”