P10 Splenic iron assessment in haemochromatosis

<h3>Introduction</h3> Haemochromatosis is an autosomal recessive disorder, most commonly owing to mutations in the HFE gene, characterised by iron accumulation due to altered homeostatic mechanisms resulting in unopposed intestinal iron absorption. Patients have low circulating levels of the iron-regulatory hormone hepcidin, causing macrophages to excessively export iron via ferroportin, resulting in an ‘iron-poor’ macrophage state. We hypothesise this iron release may result in splenic-sparing from iron deposition. Previous studies have demonstrated hepatic iron load can be quantitively assessed using magnetic resonance imaging (MRI) transverse relaxation rates (R2*). Here we aimed to use this technique to investigate splenic iron load across HFE genotypes. <h3>Methods</h3> Patients undergoing MR imaging to quantify hepatic iron load between 2015–09-01 and 2024–05-31 were assessed. Electronic health records were retrospectively analysed for demographics, HFE genotype, biochemistry and MR imaging. Imaging was reviewed using Picture Archiving and Communication Systems (PACS). Hepatic iron content (mg Fe/g) was extracted from consultant hepatobiliary radiologist imaging reports. Where MR R2* was available, mean splenic iron content was calculated from 3 circular regions of interest (ROIs) taken spatially across the organ and transverse imaging slices. Statistical analysis was conducted using a Kruskal-Wallace test and pairwise Wilcoxon rank-sum test, with Bonferroni adjustment, to assess for significant difference in hepatic and splenic iron content between different genotypes. <h3>Results</h3> 86 patients had undergone MR hepatic iron quantification, of whom 26% had R2* imaging available for splenic iron assessment (n=22). 82% had undergone HFE genotyping, with p.Cys282Tyr homozygotes (n=8), p.Cys282Tyr/p.His63Asp compound heterozygotes (n=4), p.Cys282Tyr simple heterozygotes (n=1) and patients with no HFE variant detected (n=5) represented. 4 patients had not undergone HFE genotyping, though were clinically diagnosed with transfusion-related iron overload. Median age was 61 years (IQR 44–67) and 73% of the cohort were male (n=16). In p.Cys282Tyr homozygotes, median hepatic iron content was highest (8.6 mg Fe/g, IQR 4.3–12.4), although did not significantly differ from the other genotype groups (p=0.083). Median splenic iron R2* value was lowest in p.Cys282Tyr homozygotes (median 35.5 s-1, IQR 18.8–56.8) and significantly lower than those with transfusion-related iron overload (p=0.04). <h3>Discussion</h3> C282Y homozygous patients displayed higher hepatic iron content, and lower splenic iron content than other groups studied. The significantly lower R2* median splenic iron value compared to those with secondary iron overload may suggest splenic sparing from iron accumulation in these patients. Expansion of this dataset may clarify splenic iron variation across HFE genotypes and disease severity in haemochromatosis. <h3>References</h3> Kromrey ML, Röhnert A, Blum S, Winzer R, Hoffman RT, Völzke H, Kacprowski T, Kühn JP. Whole-body R2∗ mapping to quantify tissue iron in iron storage organs: Reference values and a genotype. <i>Clinical Radiology</i>. 2021 Nov 1;<b>76</b>(11):863-e11. Brissot P, Pietrangelo A, Adams PC, De Graaff B, McLaren CE, Loréal O. Haemochromatosis. <i>Nature reviews Disease primers</i>. 2018 Apr 5;<b>4</b>(1):1–5. Pietrangelo A. Molecular insights into the pathogenesis of hereditary haemochromatosis. <i>Gut</i>. 2006 Apr 1;<b>55</b>(4):564–8. Moura E, Noordermeer MA, Verhoeven N, Verheul AF, Marx JJ. Iron release from human monocytes after erythrophagocytosis in vitro: an investigation in normal subjects and hereditary hemochromatosis patients. <i>Blood, The Journal of the American Society of Hematology</i>, 1998;<b>92</b>(7):2511–2519.