Alekya Middela, Arupam Raman, Sandhya Ramakrishna, Raj Ramakrishna, William Alexander, Jose Cuenca, Vinay Kannakurti, A. Manoharan
Background: Hyper ferritinaemia and dysfunctions in iron metabolism are common presentations encountered in clinical practice. Iron overload relates to the metabolism of iron absorption, transport and storage and can lead to significant end organ dysfunction. Iron overload has multiple causes including Hereditary Hemochromatosis (HH), which is a heterogeneous group of genetically inherited disorders of iron metabolism. There are several gene mutations responsible for the development of HH, of which, mutations in the Homeostatic Iron Regulator (HFE) gene are the most common, accounting for approximately 80% of cases. Approximately 20% of patients with HH have mutations in non-HFE genes, including genes that express hemojuvelin, hepcidin, transferrin receptor 2 and ferroportin, each of which have important functions in iron metabolism. Some examples of non-genetic causes of hyper ferritinaemia include malignancies, infections, inflammatory disorders or iatrogenic causes (e.g. frequent blood transfusions or intravenous iron infusions), and can similarly contribute to clinical manifestations of iron overload. Hence, patients with non-HFE hyper ferritinaemia treated in community clinical setting includes both uncommon mutations (non-HFE HH) and other non-hereditary causes of hyper ferritinaemia. The recommended long term treatment strategies for these non-HFE patients are yet to be established.
Aim: This study aims to evaluate clinical outcomes of patients with non-HFE hyperferritinaemia treated in the community with lifestyle modifications and venesection.
Methods: In this one-group pre-test post-test pilot study, 120 patients with non-HFE hyper ferritinaemia were studied. All patients underwent laboratory investigations including serum ferritin/transferrin saturation, inflammatory and tumour markers, Liver Function Studies (LFT), Thyroid Function Studies (TFT), Blood Sugar Level (BSL) and CT scans. Patients were provided with lifestyle modification education; in cases of persistent hyper ferritinaemia (>6 months), venesection therapy was performed. The laboratory-based investigations were repeated after minimum of six months of therapy, and this data was compared to a control group. The statistical analysis was performed using the Wilcoxon test and McNemar test.
Results: Patients pre-treatment showed significantly higher serum ferritin levels compared with controls. 37 patients (31%) demonstrated an elevated ferritin level of ≥1000m mol/L. 74 patients had abnormal LFTs at baseline. While LFTs improved in 24 (32.4%) of these patients with lifestyle modifications, 36 (48.6%) required additional venesection therapy. 14 patients (19%) showed no improvement in LFTs even with addition of venesection therapy to lifestyle modification and successful reduction in serum ferritin. 38% of patients with a BMI >30 responded adequately to intervention, of which 63% required additional venesection therapy. Furthermore, amongst non-obese patients, 57% of patients required additional venesection therapy as lifestyle measures alone was inadequate.
Conclusion: Our study showed that there was a significant improvement in clinical and laboratory markers associated with end organ dysfunction in patients with non-HFE hyper ferritinaemia when treated with lifestyle modifications and venesection therapies.