Skip to main content
WoMWeb of Medicine
SearchGraphHistory
Hematology›Condition·Updated Jul 11, 2026·v1

Hereditary Hemochromatosis

Hereditary hemochromatosis is a common genetic iron overload disorder most often due to HFE C282Y homozygosity. Diagnosis relies on elevated transferrin saturation and ferritin, confirmed by HFE genotyping. Management centers on therapeutic phlebotomy to achieve a ferritin target <50 ng/mL, with iron chelation reserved for phlebotomy-intolerant patients. Key complications include cirrhosis, hepatocellular carcinoma, cardiomyopathy, diabetes, arthropathy, and increased infection risk. Early detection and treatment prevent progression and normalize life expectancy, but established organ damage is often irreversible. Asymptomatic C282Y homozygotes benefit from regular blood donation to prevent disease.

High Evidence111 references·1,958 words·8 min read·v1
hereditary hemochromatosisHFEiron overloadhemochromatosishepcidinphlebotomygenetic disorderC282Yferritintransferrin saturation

Quick Reference

RxDrug of choiceTherapeutic phlebotomy (500 mL whole blood weekly until ferritin <50 ng/mL, then maintenance every 3-4 months to keep ferritin 50-100 ng/mL)
AltAlternativesDeferasirox (20-40 mg/kg/day PO) or deferoxamine (40-50 mg/kg/day SC/IV) for phlebotomy-intolerant patients; pantoprazole 40 mg daily as adjunct to reduce phlebotomy frequency
⊘AvoidAvoid iron supplements, high-dose vitamin C, raw shellfish, and alcohol. In acute cardiac iron overload, avoid aggressive diuretics and inotropes. Non-dihydropyridine CCBs are not specifically contraindicated but should be used with caution in cirrhosis.
DxTest of choiceTransferrin saturation (TSAT) >45% is the most sensitive screening test; HFE genotyping (C282Y, H63D) confirms diagnosis; MRI R2*/T2* quantifies liver and cardiac iron overload
ScKey scoreHepatic iron index >1.9 (by MRI or biopsy) discriminates HFE-related iron overload with AUC 0.94; serum ferritin >1000 μg/L predicts advanced fibrosis
→When to referHepatology for cirrhosis or HCC surveillance; cardiology for cardiac iron overload (T2* <10 ms); endocrinology for hypogonadism or diabetes; orthopedics for arthropathy; transplant center for decompensated cirrhosis or HCC
Suspect HH in any patient with unexplained elevated TSAT and ferritin, especially with family history or MCP joint pain. Confirm with HFE genotyping, quantify iron burden with MRI, and initiate phlebotomy to ferritin <50 ng/mL. Abstain from alcohol, avoid iron supplements, and monitor for cirrhosis, HCC, and infection. Blood donation twice yearly can prevent disease in asymptomatic C282Y homozygotes.
Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism causing progressive iron overload and end-organ damage, most commonly due to HFE gene mutations (p.C282Y) [1,3]. It is characterized by hepcidin deficiency, leading to unregulated iron absorption. Diagnosis requires elevated transferrin saturation and ferritin with genotyping. Management is phlebotomy-based. Early detection prevents cirrhosis, diabetes, and cardiomyopathy.

Overview and Recommendations

Background

  • •Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism caused by mutations that lead to hepcidin deficiency, most commonly homozygosity for the HFE C282Y variant. Hepcidin deficiency results in unregulated ferroportin-mediated iron absorption from the gut and release from macrophages, causing progressive iron loading in parenchymal organs, liver, heart, pancreas, skin, while sparing macrophages.
  • •The disease predominantly affects individuals of Northern European descent, with a C282Y homozygote frequency of approximately 1 in 200-300. However, penetrance is incomplete: only 20-38% of homozygotes develop biochemical iron overload, and just 10-33% progress to clinical disease. Men are affected earlier and more severely, with clinical onset typically after age 40; women present more often after menopause.
  • •Untreated HH carries significant morbidity: cirrhosis develops in a subset of patients with ferritin >1000 μg/L, and the risk of hepatocellular carcinoma (HCC) is markedly increased even in the absence of cirrhosis. Cardiac iron overload can cause cardiomyopathy and arrhythmias, while pancreatic iron deposition leads to diabetes. Arthropathy, especially of the second and third metacarpophalangeal joints, is common and often irreversible.
  • •Beyond HFE-related HH (type 1), four other types are recognized: juvenile HH (type 2, due to HJV or HAMP mutations) presents before age 30 with severe cardiac and endocrine involvement; type 3 (TFR2 mutations) has intermediate severity; and type 4 (ferroportin disease, SLC40A1) is autosomal dominant with macrophage iron trapping, low transferrin saturation, and often mild disease. Non-HFE forms should be suspected in young patients, those of non-European ancestry, or when iron overload persists despite negative HFE testing.
  • •The molecular basis of the hepcidin deficiency in HFE-HH involves impaired BMP/SMAD signaling: the C282Y mutant HFE fails to stabilize ALK3 on hepatocyte membranes, reducing hepcidin transcription. Genetic modifiers such as CYBRD1 and TMPRSS6 variants, as well as environmental factors like alcohol consumption and blood donation, contribute to the wide variability in clinical expression. Blood donation twice a year can reduce the risk of clinical disease in C282Y homozygotes by 80%.

Evaluation

  • •Suspect HH in any patient with unexplained fatigue, arthralgias (especially bilateral metacarpophalangeal joint pain), erectile dysfunction, or skin hyperpigmentation. A family history of liver disease, diabetes, arthritis, or cardiomyopathy should raise suspicion.
  • •Ask about alcohol intake, iron or vitamin C supplementation, blood donation history, and prior transfusions. In women, note menopausal status as ferritin rises sharply after menopause.
  • •Examine for bronze or slate-gray skin hyperpigmentation on sun-exposed areas, hepatomegaly, testicular atrophy, and stigmata of chronic liver disease (spider angiomas, palmar erythema, caput medusae). Evidence of arthritis (MCP joint swelling, limited range of motion) is a key clue.
  • •The most sensitive screening test is transferrin saturation (TSAT). A fasting TSAT >45% is the threshold for further evaluation; TSAT >60% in men or >50% in women with elevated ferritin (≥300 μg/L in men, ≥200 μg/L in women) warrants genetic testing. Serum ferritin alone is not diagnostic as it can be elevated in inflammation, metabolic syndrome, or alcohol use.
  • •Order HFE genotyping for the C282Y and H63D variants. C282Y homozygosity or compound heterozygosity (C282Y/H63D) with iron overload confirms the diagnosis. If HFE testing is negative but iron overload is confirmed (by MRI or biopsy), proceed to a non-HFE gene panel including HJV, HAMP, TFR2, and SLC40A1.
  • •Quantify liver iron concentration noninvasively with MRI R2* or T2* relaxometry, which can also assess cardiac iron. A hepatic iron index >1.9 (by biopsy or MRI) is highly specific for HFE-related iron overload. Liver biopsy is reserved for cases with discordant serology, suspected additional liver disease, or when ferroportin disease is considered (shows Kupffer cell iron trapping).
  • •Assess for end-organ damage: liver function tests, fasting glucose, echocardiogram with strain imaging, and bone density scan (DXA) at diagnosis. In patients with cirrhosis, perform semiannual HCC surveillance with ultrasound and alpha-fetoprotein.
  • •Evaluate for iron deficiency in the setting of anemia; if present, consider gastrointestinal blood loss as a cause of iron deficiency separate from HH. Do not attribute all iron overload to HH without excluding secondary causes such as transfusional iron overload, dyserythropoietic anemias, and chronic liver disease.
  • •In a patient with acute decompensation (dyspnea, hypotension, fever), obtain an urgent cardiac T2* MRI. A value <10 ms indicates life-threatening cardiac iron overload requiring immediate chelation. Simultaneously, evaluate for sepsis, keeping in mind that HH patients have a 1.7-fold increased risk of sepsis and are susceptible to siderophilic organisms like Yersinia and Vibrio.
  • •Diagnostic criteria for HH: evidence of increased iron stores (elevated TSAT and ferritin, or MRI/biopsy evidence) plus either homozygosity for C282Y or compound heterozygosity for C282Y/H63D. In non-HFE types, the genetic defect defines the subtype. A normal TSAT (<45%) effectively excludes hepcidin-deficient HH, even with hyperferritinemia.

Management

  • •Initiate therapeutic phlebotomy as first-line therapy for all patients with iron overload. Induction: remove 500 mL of whole blood (≈200 mg iron) weekly or biweekly until serum ferritin falls below 50 ng/mL. Maintain hemoglobin ≥11 g/dL; defer phlebotomy if lower. The typical induction course requires 20-40 sessions over 6-12 months.
  • •After iron depletion, transition to maintenance phlebotomy every 3-4 months to keep serum ferritin between 50 and 100 ng/mL. For asymptomatic C282Y homozygotes without iron overload, regular blood donation at least twice a year reduces the risk of developing clinical disease to that of a low-risk compound heterozygote.
  • •Iron chelation (deferasirox 20-40 mg/kg/day orally or deferoxamine 40-50 mg/kg/day subcutaneously) is reserved for patients who cannot tolerate phlebotomy due to severe anemia (Hb persistently <11 g/dL), poor venous access, or advanced cirrhosis with thrombocytopenia. Chelation is less effective and more expensive than phlebotomy.
  • •In acute cardiac iron overload (T2* <10 ms), start continuous intravenous deferoxamine at 40-50 mg/kg over 24 hours without interruption. Do not use aggressive diuretics or inotropes, as the high-output state in chronic anemia makes these patients sensitive to volume shifts. Add oral deferiprone (75 mg/kg/day divided TID) as augmentation if needed. Continue until cardiac T2* improves to >10 ms.
  • •For suspected sepsis in HH, obtain blood cultures and start empiric antibiotics covering Yersinia enterocolitica and Vibrio vulnificus: ceftriaxone 2 g IV daily plus doxycycline 100 mg IV twice daily. Consider temporarily withholding deferoxamine if Yersinia infection is confirmed, as it may act as a siderophore. The infection risk persists even with normal ferritin.
  • •Advise all patients to abstain from alcohol completely, as alcohol accelerates hepatic fibrosis and increases cirrhosis risk. Avoid iron supplements, high-dose vitamin C (which enhances iron absorption and oxidative stress), and raw shellfish. A balanced diet low in red meat is reasonable. Ilex paraguariensis (yerba mate) tea can inhibit non-heme iron absorption.
  • •Consider adjunctive pantoprazole 40 mg daily in patients with high phlebotomy requirements; it reduces dietary iron absorption by increasing gastric pH and may decrease the frequency of phlebotomy.
  • •Monitor patients on maintenance therapy: serum ferritin and TSAT every 3-6 months, plus annual liver function tests, fasting glucose, and joint assessment. In patients with cirrhosis, perform semiannual HCC surveillance with ultrasound and alpha-fetoprotein. Repeat cardiac MRI every 1-2 years if there is evidence of myocardial iron deposition.
  • •Manage hypogonadotropic hypogonadism with testosterone replacement if symptomatic. Treat osteoporosis (DXA-confirmed) with bisphosphonates or denosumab, and ensure adequate calcium and vitamin D intake. Refer to an endocrinologist for complex cases.
  • •For arthropathy, provide symptomatic treatment with NSAIDs or acetaminophen; consider orthopedic referral as joint replacement is more common in HH (6.3% of patients undergo arthroplasty). Iron-mediated arthropathy progresses faster than osteoarthritis.
  • •Anticoagulation for atrial fibrillation follows standard CHA₂DS₂-VASc risk assessment, but use direct oral anticoagulants with caution in patients with cirrhosis and avoid in decompensated disease. Portal vein thrombosis in cirrhosis requires anticoagulation per general guidelines.
  • •What NOT to do: Do not use iron chelation as first-line therapy; do not ignore alcohol counseling; do not perform phlebotomy in patients with hemoglobin <11 g/dL without evaluating the cause of anemia; do not supplement with vitamin C without monitoring iron status; do not use aggressive diuretics in acute cardiac iron overload; do not withhold antibiotics while awaiting cultures in a febrile HH patient.
  • •Refer to hepatology for cirrhosis or HCC, cardiology for cardiac iron overload, endocrinology for hypogonadism or diabetes, orthopedics for arthropathy, and a transplant center for end-stage liver disease. For pregnant women with HH, defer phlebotomy unless severe overload; avoid iron supplementation unless documented iron deficiency. Postpartum, reassess ferritin, especially after menopause.

Board Review — High Yield

  • •C282Y homozygosity, Most common genotype in HH; 1 in 200-300 Northern Europeans; penetrance only ~20%
  • •TSAT >45%, Most sensitive screening test; a normal TSAT effectively excludes hepcidin-deficient HH
  • •Ferritin >1000 μg/L, Strongest predictor of advanced fibrosis; urgent phlebotomy indicated
  • •Phlebotomy first-line, Induction weekly 500 mL until ferritin <50 ng/mL; maintenance every 3-4 months
  • •Blood donation twice yearly, Reduces risk of clinical HH in C282Y homozygotes by 80% (to level of compound heterozygote)
  • •Alcohol abstinence, Essential to prevent fibrosis progression; alcohol is a major cofactor
  • •Infection risk persists, C282Y homozygotes have HR 1.40 for any infection, 1.69 for sepsis, even with normal iron indices
  • •Juvenile HH (HJV/HAMP), Onset <30 years; severe cardiomyopathy and hypogonadism; requires early aggressive treatment
  • •Postmenopausal ferritin surge, 3.6-fold increase in 10 years in C282Y homozygotes; proactive phlebotomy needed
  • •Cardiac T2 <10 ms*, Indicates acute cardiac iron overload; treat with continuous IV deferoxamine 40-50 mg/kg/24h, avoid diuretics

Deep Dive — Evidence Details

References

  1. [1]

    Whitlock EP, Garlitz BA, Harris EL et al.. “Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force.” Annals of internal medicine (2006). PMID: 16880463 ↗

    L2SR_OBSCited in: 1. Definition, Classification & Nomenclature
  2. [2]

    Wändell P, Li X, Carlsson AC et al.. “The risk of hemochromatosis among first- and second-generation immigrants: a cohort study of the total population in Sweden.” Upsala journal of medical sciences (2024). PMID: 39257474 ↗

    L2COHORTCited in: 1. Definition, Classification & Nomenclature, 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling
  3. [3]

    Camaschella C, Poggiali E. “Inherited disorders of iron metabolism.” Current opinion in pediatrics (2011). PMID: 21150441 ↗

    L5REVIEW_NARRATIVECited in: 1. Definition, Classification & Nomenclature
  4. [4]

    Baas FS, Rishi G, Swinkels DW et al.. “Genetic Diagnosis in Hereditary Hemochromatosis: Discovering and Understanding the Biological Relevance of Variants.” Clinical chemistry (2021). PMID: 34402502 ↗

    L5REVIEW_NARRATIVECited in: 1. Definition, Classification & Nomenclature
  5. [5]

    Cherfane CE, Hollenbeck RD, Go J et al.. “Hereditary hemochromatosis: missed diagnosis or misdiagnosis?” The American journal of medicine (2013). PMID: 24054178 ↗

    L4OTHERCited in: 1. Definition, Classification & Nomenclature
  6. [6]

    Loughnan R, Ahern J, Tompkins C et al.. “Association of Genetic Variant Linked to Hemochromatosis With Brain Magnetic Resonance Imaging Measures of Iron and Movement Disorders.” JAMA neurology (2022). PMID: 35913729 ↗

    L4OTHERCited in: 1. Definition, Classification & Nomenclature
  7. [7]

    Constantine CC, Anderson GJ, Vulpe CD et al.. “A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis.” British journal of haematology (2009). PMID: 19673882 ↗

    L2COHORTCited in: 2. Pathophysiology & Mechanism, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  8. [8]

    Wood MJ, Powell LW, Ramm GA. “Environmental and genetic modifiers of the progression to fibrosis and cirrhosis in hemochromatosis.” Blood (2008). PMID: 18316631 ↗

    L5REVIEW_NARRATIVECited in: 2. Pathophysiology & Mechanism, 8. Long-term & Definitive Management, History and Evolution of Treatment, 11. Complications, 12. Prognosis & Natural History
  9. [9]

    Koch PS, Olsavszky V, Ulbrich F et al.. “Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis.” Blood (2016). PMID: 27903529 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  10. [10]

    Finberg KE, Whittlesey RL, Andrews NC. “Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice.” Blood (2011). PMID: 21355094 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism
  11. [11]

    Kautz L, Meynard D, Besson-Fournier C et al.. “BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression.” Blood (2009). PMID: 19622835 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism
  12. [12]

    Wu XG, Wang Y, Wu Q et al.. “HFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression.” Blood (2014). PMID: 24904118 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism
  13. [13]

    Steinbicker AU, Bartnikas TB, Lohmeyer LK et al.. “Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice.” Blood (2011). PMID: 21841161 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism
  14. [14]

    Vujic Spasic M, Kiss J, Herrmann T et al.. “Physiologic systemic iron metabolism in mice deficient for duodenal Hfe.” Blood (2007). PMID: 17264297 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism
  15. [15]

    Schmidt PJ, Andrews NC, Fleming MD. “Hepcidin induction by transgenic overexpression of Hfe does not require the Hfe cytoplasmic tail, but does require hemojuvelin.” Blood (2010). PMID: 20837779 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism
  16. [16]

    Allen KJ, Gurrin LC, Constantine CC et al.. “Iron-overload-related disease in HFE hereditary hemochromatosis.” The New England journal of medicine (2008). PMID: 18199861 ↗

    L2OTHERCited in: 2. Pathophysiology & Mechanism, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), History and Evolution of Treatment
  17. [17]

    Yu Y, Woloshun RR, Lee JK et al.. “In vivo silencing of intestinal DMT1 mitigates iron loading in β-thalassemia intermedia (Hbbth3/+) mice.” Blood advances (2024). PMID: 39250719 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism, 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  18. [18]

    Pietrangelo A. “Ferroportin disease: pathogenesis, diagnosis and treatment.” Haematologica (2017). PMID: 29101207 ↗

    L5REVIEW_NARRATIVECited in: 2. Pathophysiology & Mechanism, 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling, 8. Long-term & Definitive Management, 14. Prevention, Screening & Surveillance
  19. [19]

    Hollerer I, Bachmann A, Muckenthaler MU. “Pathophysiological consequences and benefits of HFE mutations: 20 years of research.” Haematologica (2017). PMID: 28280078 ↗

    L5REVIEW_NARRATIVECited in: 2. Pathophysiology & Mechanism, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), History and Evolution of Treatment
  20. [20]

    Liu J, Liu W, Liu Y et al.. “New thiazolidinones reduce iron overload in mouse models of hereditary hemochromatosis and β-thalassemia.” Haematologica (2019). PMID: 30792208 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism, 3. Epidemiology, Etiology & Risk Factors, 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  21. [21]

    Pelucchi S, Mariani R, Calza S et al.. “CYBRD1 as a modifier gene that modulates iron phenotype in HFE p.C282Y homozygous patients.” Haematologica (2012). PMID: 22773607 ↗

    L4OTHERCited in: 2. Pathophysiology & Mechanism, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), 12. Prognosis & Natural History
  22. [22]

    Origa R, Galanello R, Ganz T et al.. “Liver iron concentrations and urinary hepcidin in beta-thalassemia.” Haematologica (2007). PMID: 17488680 ↗

    L3OTHERCited in: 2. Pathophysiology & Mechanism, 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  23. [23]

    Aguilar-Martinez P, Grandchamp B, Cunat S et al.. “Iron overload in HFE C282Y heterozygotes at first genetic testing: a strategy for identifying rare HFE variants.” Haematologica (2011). PMID: 21228038 ↗

    L4OTHERCited in: 2. Pathophysiology & Mechanism, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  24. [24]

    Majore S, Milano F, Binni F et al.. “Homozygous p.M172K mutation of the TFR2 gene in an Italian family with type 3 hereditary hemochromatosis and early onset iron overload.” Haematologica (2006). PMID: 16923517 ↗

    L4OTHERCited in: 2. Pathophysiology & Mechanism, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  25. [25]

    Akbarialiabad H, Jamshidi P, Callen JP et al.. “Dermatologic manifestations of hereditary hemochromatosis: A systematic review.” Journal of the European Academy of Dermatology and Venereology : JEADV (2024). PMID: 38752605 ↗

    L2SR_OBSCited in: 2. Pathophysiology & Mechanism, 4. Clinical Presentation, 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling
  26. [26]

    Hoxha M, Malaj V, Zappacosta B. “Health Economic Evaluations of Hemochromatosis Screening and Treatment: A Systematic Review.” PharmacoEconomics - open (2024). PMID: 38279979 ↗

    L2SR_OBSCited in: 2. Pathophysiology & Mechanism, 8. Long-term & Definitive Management, 14. Prevention, Screening & Surveillance
  27. [27]

    Wang J, Xu J, Jiang N et al.. “Case report: A rare case of hereditary hemochromatosis caused by a mutation in the HAMP gene in Fuyang, China.” Frontiers in medicine (2024). PMID: 39005658 ↗

    L4CASE_REPORTCited in: 2. Pathophysiology & Mechanism, 4. Clinical Presentation, 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling
  28. [28]

    Tamai Y, Hosotani M, Shigefuku R et al.. “Novel mutation of transferrin receptor 2 causing hereditary hemochromatosis type 3 in a Japanese patient.” Hepatology research : the official journal of the Japan Society of Hepatology (2024). PMID: 38850209 ↗

    L4CASE_REPORTCited in: 2. Pathophysiology & Mechanism, 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling
  29. [29]

    Das S, Majumder S, Saqib M et al.. “Expansion of CD101⁻ neutrophils drives susceptibility to hyperyersiniabactin-producing Yersinia infection in hereditary hemochromatotic hosts.” Infection and immunity (2026). PMID: 42283579 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism, 4. Clinical Presentation, 7. Acute & Emergency Management, 11. Complications, 12. Prognosis & Natural History
  30. [30]

    Hamann V, Hook S, Sujariyakul P et al.. “In vivo base editing alleviates hepatic iron accumulation and fibrosis in models of HFE-related hereditary hemochromatosis.” Journal of hepatology (2026). PMID: 42269836 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism, 6. Staging, Risk Stratification & Prognostic Scoring, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  31. [31]

    Gendrot B, Peyssonnaux C, Plo I et al.. “Impaired iron balance and erythrocytosis: a complex relationship.” Blood cancer journal (2026). PMID: 42120370 ↗

    L5REVIEW_NARRATIVECited in: 2. Pathophysiology & Mechanism, 4. Clinical Presentation, 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  32. [32]

    Xiao X, Moschetta GA, Chowdhury SB et al.. “Hemochromatosis Proteins Hemojuvelin and Homeostatic Iron Regulator in Bone Morphogenetic Protein-Mediated Hepcidin Regulation and Iron Homeostasis.” American journal of hematology (2025). PMID: 40913261 ↗

    L5OTHERCited in: 2. Pathophysiology & Mechanism
  33. [33]

    Kong X, Xie L, Zhu H et al.. “Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review.” Orphanet journal of rare diseases (2019). PMID: 31286966 ↗

    L4SR_OBSCited in: 3. Epidemiology, Etiology & Risk Factors, 12. Prognosis & Natural History
  34. [34]

    Buttignol M, Bouche C, Chrétien M et al.. “Hemochromatosis: A Risk Factor for Breast Cancer? Systematic Review and Meta-Analysis.” European journal of breast health (2025). PMID: 40910550 ↗

    L2SR_OBSCited in: 3. Epidemiology, Etiology & Risk Factors, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), 12. Prognosis & Natural History, 14. Prevention, Screening & Surveillance
  35. [35]

    Wijarnpreecha K, Aby ES, Panjawatanan P et al.. “Hereditary hemochromatosis and risk of joint replacement surgery: a systematic review and meta-analysis.” European journal of gastroenterology & hepatology (2021). PMID: 32118852 ↗

    L2SR_OBSCited in: 3. Epidemiology, Etiology & Risk Factors, 4. Clinical Presentation
  36. [36]

    McPhail MJW, Khorsandi SE, Abbott L et al.. “Modern Outcomes Following Treatment of Hepatocellular Carcinoma in Hereditary Hemochromatosis: A Matched Cohort Study.” American journal of clinical oncology (2019). PMID: 31436748 ↗

    L2COHORTCited in: 3. Epidemiology, Etiology & Risk Factors, 6. Staging, Risk Stratification & Prognostic Scoring, 11. Complications, 12. Prognosis & Natural History
  37. [37]

    Toivonen J, Clancy J, Åberg F et al.. “Quantifying risk modifiers of hereditary hemochromatosis using genomic and electronic health record data.” JHEP reports : innovation in hepatology (2026). PMID: 41861673 ↗

    L2OTHERCited in: 3. Epidemiology, Etiology & Risk Factors, 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling, 8. Long-term & Definitive Management, 14. Prevention, Screening & Surveillance
  38. [38]

    Suresh D, Li A, Miller MJ et al.. “Associations between metabolic hyperferritinaemia, fibrosis-promoting alleles and clinical outcomes in steatotic liver disease.” Liver international : official journal of the International Association for the Study of the Liver (2023). PMID: 37971775 ↗

    L3OTHERCited in: 3. Epidemiology, Etiology & Risk Factors
  39. [39]

    Calori S, Comisi C, Mascio A et al.. “Overview of Ankle Arthropathy in Hereditary Hemochromatosis.” Medical sciences (Basel, Switzerland) (2023). PMID: 37606430 ↗

    L5REVIEW_NARRATIVECited in: 3. Epidemiology, Etiology & Risk Factors
  40. [40]

    Zin OA, Neves LM, Cunha DP et al.. “Genotypic-Phenotypic Correlations of Hereditary Hyperferritinemia-Cataract Syndrome: Case Series of Three Brazilian Families.” International journal of molecular sciences (2023). PMID: 37569253 ↗

    L4CASE_REPORTCited in: 4. Clinical Presentation, 13. Special Populations & Pregnancy
  41. [41]

    Cristancho LCQ, Urbano MA, Nati-Castillo HA et al.. “A decade of iron overload disorders and hemochromatosis: clinical and genetic findings from a specialized center in Colombia.” Frontiers in medicine (2024). PMID: 39720661 ↗

    L4OTHERCited in: 4. Clinical Presentation
  42. [42]

    Sandhu K, Flintoff K, Chatfield MD et al.. “Phenotypic analysis of hemochromatosis subtypes reveals variations in severity of iron overload and clinical disease.” Blood (2018). PMID: 29743178 ↗

    L4OTHERCited in: 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), History and Evolution of Treatment, 12. Prognosis & Natural History
  43. [43]

    D'Onofrio V, Esposito FM, Marra R et al.. “Clinical variability of ATP11C-related hemolytic anemia: expanding the phenotypic and diagnostic spectrum.” Blood advances (2026). PMID: 42018644 ↗

    L4OTHERCited in: 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), 12. Prognosis & Natural History
  44. [44]

    Bergamaschi G, Markopoulos K, Albertini R et al.. “Anemia of chronic disease and defective erythropoietin production in patients with celiac disease.” Haematologica (2008). PMID: 18815191 ↗

    L4OTHERCited in: 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling
  45. [45]

    . “[Chinese guidelines for the diagnosis and treatment of hereditary hemochromatosis].” Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology (2024). PMID: 39375100 ↗

    L1GUIDELINECited in: 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling, 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), History and Evolution of Treatment
  46. [46]

    Morel P, Silva Rodriguez M, Benmouffek C et al.. “Clinical Exome Sequencing in Unexplained Hyperferritinemia Reveals Digenic and Oligogenic Inheritance Beyond Iron Homeostasis.” Liver international : official journal of the International Association for the Study of the Liver (2026). PMID: 41968586 ↗

    L4OTHERCited in: 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  47. [47]

    Yang Y, Zu Z, Huang Y. “Hemochromatosis osteoarthritis.” Frontiers in endocrinology (2026). PMID: 41928889 ↗

    L5REVIEW_NARRATIVECited in: 5. Diagnosis & Workup: Smear, Marrow, Flow Cytometry & Molecular Profiling, 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  48. [48]

    de Swart L, Hendriks JC, van der Vorm LN et al.. “Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders.” Haematologica (2015). PMID: 26385212 ↗

    L4OTHERCited in: 6. Staging, Risk Stratification & Prognostic Scoring, 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  49. [49]

    Moyer TP, Highsmith WE, Smyrk TC et al.. “Hereditary hemochromatosis: laboratory evaluation.” Clinica chimica acta; international journal of clinical chemistry (2011). PMID: 21510925 ↗

    L5REVIEW_NARRATIVECited in: 6. Staging, Risk Stratification & Prognostic Scoring
  50. [50]

    Karim A, Bajbouj K, Qaisar R et al.. “The role of disrupted iron homeostasis in the development and progression of arthropathy.” Journal of orthopaedic research : official publication of the Orthopaedic Research Society (2022). PMID: 35289955 ↗

    L5REVIEW_NARRATIVECited in: 6. Staging, Risk Stratification & Prognostic Scoring
  51. [51]

    Theise ND. “Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach.” Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (2007). PMID: 17486049 ↗

    L5REVIEW_NARRATIVECited in: 6. Staging, Risk Stratification & Prognostic Scoring
  52. [52]

    Hernando D, Levin YS, Sirlin CB et al.. “Quantification of liver iron with MRI: state of the art and remaining challenges.” Journal of magnetic resonance imaging : JMRI (2014). PMID: 24585403 ↗

    L5REVIEW_NARRATIVECited in: 6. Staging, Risk Stratification & Prognostic Scoring
  53. [53]

    Zhou X, Jia X, Chen Y et al.. “Computed Tomography and Magnetic Resonance Imaging in Liver Iron Overload: From Precise Quantification to Prognosis Assessment.” Biomedicines (2024). PMID: 39595022 ↗

    L5REVIEW_NARRATIVECited in: 6. Staging, Risk Stratification & Prognostic Scoring, 8. Long-term & Definitive Management
  54. [54]

    Sivasubramaniam P, Stokes N, Patil A et al.. “Digital Hepatic Iron Content: An Artificial Intelligence Model for Spatially Resolved Histologic Iron Quantitative Analysis in Liver Samples.” Laboratory investigation; a journal of technical methods and pathology (2023). PMID: 37331629 ↗

    L4OTHERCited in: 6. Staging, Risk Stratification & Prognostic Scoring
  55. [55]

    Mottelson M, Glenthøj A, Nordestgaard BG et al.. “Iron, hemochromatosis genotypes, and risk of infections: a cohort study of 142 188 general population individuals.” Blood (2024). PMID: 38728387 ↗

    L2COHORTCited in: 7. Acute & Emergency Management, 11. Complications
  56. [56]

    Pennell DJ, Udelson JE, Arai AE et al.. “Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association.” Circulation (2013). PMID: 23775258 ↗

    L5GUIDELINECited in: 7. Acute & Emergency Management
  57. [57]

    Xu T, Zhang X, Zhao W et al.. “Foxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasis.” Blood (2024). PMID: 38848533 ↗

    L5OTHERCited in: 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  58. [58]

    Tsay J, Yang Z, Ross FP et al.. “Bone loss caused by iron overload in a murine model: importance of oxidative stress.” Blood (2010). PMID: 20554970 ↗

    L5OTHERCited in: 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  59. [59]

    Ramos E, Ruchala P, Goodnough JB et al.. “Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis.” Blood (2012). PMID: 22990014 ↗

    L5OTHERCited in: 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), 14. Prevention, Screening & Surveillance
  60. [60]

    Schmidt PJ, Toudjarska I, Sendamarai AK et al.. “An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine β-thalassemia intermedia.” Blood (2012). PMID: 23223430 ↗

    L5OTHERCited in: 8. Long-term & Definitive Management, 12. Prognosis & Natural History
  61. [61]

    Ramos P, Guy E, Chen N et al.. “Enhanced erythropoiesis in Hfe-KO mice indicates a role for Hfe in the modulation of erythroid iron homeostasis.” Blood (2010). PMID: 21059897 ↗

    L5OTHERCited in: 8. Long-term & Definitive Management
  62. [62]

    van Deuren M, Kroot JJ, Swinkels DW. “Time-course analysis of serum hepcidin, iron and cytokines in a C282Y homozygous patient with Schnitzler's syndrome treated with IL-1 receptor antagonist.” Haematologica (2009). PMID: 19608676 ↗

    L4CASE_REPORTCited in: 8. Long-term & Definitive Management
  63. [63]

    Yu Y, Lu L, Fan X et al.. “Case Report: Secukinumab for the treatment of severe psoriasis in a patient with hereditary hemochromatosis.” Frontiers in medicine (2025). PMID: 40861231 ↗

    L4CASE_REPORTCited in: 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  64. [64]

    Colangelo L, Terracina S, Sonato C et al.. “Exploring the dynamics of FGF23 in patients with Hereditary Hemochromatosis type I following iron depletive treatment: a pilot study.” Journal of endocrinological investigation (2026). PMID: 42189479 ↗

    L2OTHERCited in: 8. Long-term & Definitive Management, 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  65. [65]

    Blaney H, Waterman A, Kaplan A. “Impact of Alcohol Use on Nonalcohol-Related Liver Diseases.” Clinics in liver disease (2025). PMID: 41266012 ↗

    L5REVIEW_NARRATIVECited in: 8. Long-term & Definitive Management
  66. [66]

    Harrer A, Meyron-Holtz EG, Meinhardt A. “The role of iron in normal and impaired testicular function.” Andrology (2025). PMID: 40464377 ↗

    L5REVIEW_NARRATIVECited in: 8. Long-term & Definitive Management, 11. Complications
  67. [67]

    Leaf RK, Dickey AK. “Porphyria cutanea tarda: a unique iron-related disorder.” Hematology. American Society of Hematology. Education Program (2024). PMID: 39644053 ↗

    L5REVIEW_NARRATIVECited in: 8. Long-term & Definitive Management, 11. Complications
  68. [68]

    Girelli D, Marchi G, Busti F. “Diagnosis and management of hereditary hemochromatosis: lifestyle modification, phlebotomy, and blood donation.” Hematology. American Society of Hematology. Education Program (2024). PMID: 39644049 ↗

    L5REVIEW_NARRATIVECited in: 8. Long-term & Definitive Management
  69. [69]

    Chen S, Osborn JD, Chen X et al.. “Subacute hepatic necrosis mimicking veno-occlusive disease in a patient with HFE H63D homozygosity after allogeneic hematopoietic cell transplantation with busulfan conditioning.” International journal of hematology (2015). PMID: 26497867 ↗

    L4CASE_REPORTCited in: 9. Hematopoietic Cell Transplantation & Cellular Therapy
  70. [70]

    Stussi G, Buser A, Holbro A. “Red Blood Cells: Exchange, Transfuse, or Deplete.” Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie (2019). PMID: 31933570 ↗

    L5REVIEW_NARRATIVECited in: 9. Hematopoietic Cell Transplantation & Cellular Therapy
  71. [71]

    Alharbi I, Bahakim AK, Alharthi SM et al.. “Hereditary Hemochromatosis Associated With Idiopathic Refractory Aplastic Anemia in a Five-Year-Old Boy: A Case Report.” Cureus (2021). PMID: 35003970 ↗

    L4CASE_REPORTCited in: 9. Hematopoietic Cell Transplantation & Cellular Therapy
  72. [72]

    Azcárate IG, Sánchez-Jaut S, Marín-García P et al.. “Iron supplementation in mouse expands cellular innate defences in spleen and defers lethal malaria infection.” Biochimica et biophysica acta. Molecular basis of disease (2017). PMID: 28965885 ↗

    L5OTHERCited in: 9. Hematopoietic Cell Transplantation & Cellular Therapy
  73. [73]

    Zhao W, Wang P, Liu Z et al.. “The endothelial mTORC2-Foxo1 axis serves as an iron-responsive sensor governing systemic iron homeostasis.” Blood (2025). PMID: 40561335 ↗

    L5OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  74. [74]

    Wang CY, Babitt JL. “Liver iron sensing and body iron homeostasis.” Blood (2018). PMID: 30401708 ↗

    L5REVIEW_NARRATIVECited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), 11. Complications
  75. [75]

    Gleadall NS, Koets L, Shamardina O et al.. “Array genotyping of transfusion-relevant blood cell antigens in 6946 ancestrally diverse study participants.” Blood (2025). PMID: 40499009 ↗

    L4OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  76. [76]

    Banerjee S, Lu S, Jain A et al.. “Targeting PKCα alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin.” Blood (2024). PMID: 38861671 ↗

    L5OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  77. [77]

    Lok CY, Merryweather-Clarke AT, Viprakasit V et al.. “Iron overload in the Asian community.” Blood (2009). PMID: 19342478 ↗

    L5OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  78. [78]

    Fernandes A, Preza GC, Phung Y et al.. “The molecular basis of hepcidin-resistant hereditary hemochromatosis.” Blood (2009). PMID: 19383972 ↗

    L5OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  79. [79]

    Ajioka RS, Phillips JD, Weiss RB et al.. “Down-regulation of hepcidin in porphyria cutanea tarda.” Blood (2008). PMID: 18809758 ↗

    L3OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  80. [80]

    Renassia C, Louis S, Cuvellier S et al.. “Neutrophils from hereditary hemochromatosis patients are protected from iron excess and are primed.” Blood advances (2020). PMID: 32810223 ↗

    L4OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), 11. Complications
  81. [81]

    Nairz M, Metzendorf C, Vujic-Spasic M et al.. “Cell-specific expression of Hfe determines the outcome of Salmonella enterica serovar Typhimurium infection in mice.” Haematologica (2021). PMID: 33054105 ↗

    L5OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), 11. Complications, 12. Prognosis & Natural History
  82. [82]

    De Domenico I, Ward DM, Musci G et al.. “Iron overload due to mutations in ferroportin.” Haematologica (2006). PMID: 16434376 ↗

    L5REVIEW_NARRATIVECited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  83. [83]

    Fung E, Nemeth E. “Manipulation of the hepcidin pathway for therapeutic purposes.” Haematologica (2013). PMID: 24186312 ↗

    L5REVIEW_NARRATIVECited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  84. [84]

    Gutschow P, Schmidt PJ, Han H et al.. “A competitive enzyme-linked immunosorbent assay specific for murine hepcidin-1: correlation with hepatic mRNA expression in established and novel models of dysregulated iron homeostasis.” Haematologica (2014). PMID: 25425686 ↗

    L5OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  85. [85]

    Lou A, Elnenaei MO, Zhu J et al.. “Re-evaluating the utility of iron indices in hereditary hemochromatosis genotyping: A retrospective study.” Clinical biochemistry (2024). PMID: 39617311 ↗

    L2COHORTCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management)
  86. [86]

    Yu Y, Jiang L, Lin Z et al.. “Modulation of the E3-ubiquitin ligase RNF217 alters ferroportin levels in enterocytes and iron loading in murine hemochromatosis.” Blood (2026). PMID: 42008384 ↗

    L5OTHERCited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), History and Evolution of Treatment, 11. Complications
  87. [87]

    Młodziński K, Świątczak M, Kaufmann D et al.. “From Iron Deficiency to Overload: A Missing Link in the Mechanisms of Cardiac Autonomic Nervous System Dysfunction.” Journal of clinical medicine (2026). PMID: 41827288 ↗

    L5REVIEW_NARRATIVECited in: 10. Transfusion, Anticoagulation & Cytoreduction (Hematology-Distinctive Management), 14. Prevention, Screening & Surveillance
  88. [88]

    Brandão M, Oliveira JC, Bravo F et al.. “The soluble transferrin receptor as a marker of iron homeostasis in normal subjects and in HFE-related hemochromatosis.” Haematologica (2005). PMID: 15642666 ↗

    L4RCTCited in: History and Evolution of Treatment
  89. [89]

    Kowdley KV, Brown KE, Ahn J et al.. “ACG Clinical Guideline: Hereditary Hemochromatosis.” The American journal of gastroenterology (2019). PMID: 31335359 ↗

    L1GUIDELINECited in: History and Evolution of Treatment
  90. [90]

    Adams P, Altes A, Brissot P et al.. “Therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype.” Hepatology international (2018). PMID: 29589198 ↗

    L1GUIDELINECited in: History and Evolution of Treatment
  91. [91]

    Kwo PY, Cohen SM, Lim JK. “ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries.” The American journal of gastroenterology (2016). PMID: 27995906 ↗

    L1GUIDELINECited in: History and Evolution of Treatment, 12. Prognosis & Natural History, 14. Prevention, Screening & Surveillance
  92. [92]

    Olynyk JK, Cullen DJ, Aquilia S et al.. “A population-based study of the clinical expression of the hemochromatosis gene.” The New England journal of medicine (1999). PMID: 10471457 ↗

    L2OTHERCited in: History and Evolution of Treatment
  93. [93]

    Buerkli S, Salvioni L, Koller N et al.. “The effect of a natural polyphenol supplement on iron absorption in adults with hereditary hemochromatosis.” European journal of nutrition (2022). PMID: 35320401 ↗

    L1RCTCited in: History and Evolution of Treatment
  94. [94]

    Pagliosa CM, Vieira FGK, Dias BV et al.. “Ilex paraguariensis (A. St.-Hil.) leaf infusion decreases iron absorption in patients with hereditary hemochromatosis: a randomized controlled crossover study.” Food & function (2021). PMID: 34173816 ↗

    L1RCTCited in: History and Evolution of Treatment, 14. Prevention, Screening & Surveillance
  95. [95]

    Lobbes H, Gladine C, Mazur A et al.. “Effect of procyanidin on dietary iron absorption in hereditary hemochromatosis and in dysmetabolic iron overload syndrome: A crossover double-blind randomized controlled trial.” Clinical nutrition (Edinburgh, Scotland) (2019). PMID: 30792142 ↗

    L1RCTCited in: History and Evolution of Treatment
  96. [96]

    Vanclooster A, van Deursen C, Jaspers R et al.. “Proton Pump Inhibitors Decrease Phlebotomy Need in HFE Hemochromatosis: Double-Blind Randomized Placebo-Controlled Trial.” Gastroenterology (2017). PMID: 28624580 ↗

    L1RCTCited in: History and Evolution of Treatment
  97. [97]

    Barosi G, Salvaneschi L, Grasso M et al.. “High prevalence of a screening-detected, HFE-unrelated, mild idiopathic iron overload in Northern Italy.” Haematologica (2002). PMID: 12010659 ↗

    L2OTHERCited in: History and Evolution of Treatment
  98. [98]

    Fattizzo B, Giannotta JA, Cecchi N et al.. “Confounding factors in the diagnosis and clinical course of rare congenital hemolytic anemias.” Orphanet journal of rare diseases (2021). PMID: 34627331 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  99. [99]

    Forciniti S, Greco L, Grizzi F et al.. “Iron Metabolism in Cancer Progression.” International journal of molecular sciences (2020). PMID: 32214052 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  100. [100]

    Labranche R, Gilbert G, Cerny M et al.. “Liver Iron Quantification with MR Imaging: A Primer for Radiologists.” Radiographics : a review publication of the Radiological Society of North America, Inc (2018). PMID: 29528818 ↗

    L5REVIEW_NARRATIVECited in: History and Evolution of Treatment
  101. [101]

    Nairz M, Theurl I, Schroll A et al.. “Absence of functional Hfe protects mice from invasive Salmonella enterica serovar Typhimurium infection via induction of lipocalin-2.” Blood (2009). PMID: 19700664 ↗

    L5OTHERCited in: 11. Complications, 12. Prognosis & Natural History
  102. [102]

    Baschant U, Altamura S, Steele-Perkins P et al.. “Iron effects versus metabolic alterations in hereditary hemochromatosis driven bone loss.” Trends in endocrinology and metabolism: TEM (2022). PMID: 35871125 ↗

    L5REVIEW_NARRATIVECited in: 11. Complications
  103. [103]

    Sarigianni M, Liakos A, Vlachaki E et al.. “Accuracy of magnetic resonance imaging in diagnosis of liver iron overload: a systematic review and meta-analysis.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2014). PMID: 24993364 ↗

    L1SR_OBSCited in: 12. Prognosis & Natural History, 14. Prevention, Screening & Surveillance
  104. [104]

    Warne CD, Zaloumis SG, Bertalli NA et al.. “HFE p.C282Y homozygosity predisposes to rapid serum ferritin rise after menopause: A genotype-stratified cohort study of hemochromatosis in Australian women.” Journal of gastroenterology and hepatology (2017). PMID: 27784128 ↗

    L2COHORTCited in: 13. Special Populations & Pregnancy
  105. [105]

    Savatt JM, Wagner JK, Joffe S et al.. “Pediatric reporting of genomic results study (PROGRESS): a mixed-methods, longitudinal, observational cohort study protocol to explore disclosure of actionable adult- and pediatric-onset genomic variants to minors and their parents.” BMC pediatrics (2020). PMID: 32414353 ↗

    L5TRIAL_NONRANDOMCited in: 13. Special Populations & Pregnancy
  106. [106]

    Trost LB, Bergfeld WF, Calogeras E. “The diagnosis and treatment of iron deficiency and its potential relationship to hair loss.” Journal of the American Academy of Dermatology (2006). PMID: 16635664 ↗

    L5REVIEW_NARRATIVECited in: 13. Special Populations & Pregnancy
  107. [107]

    Lee JK, He Y, Flores SR et al.. “Development of rat and mouse models of heme-iron absorption.” JCI insight (2025). PMID: 40485584 ↗

    L5OTHERCited in: 13. Special Populations & Pregnancy
  108. [108]

    Doguer C, Ha JH, Collins JF. “Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver.” Comprehensive Physiology (2018). PMID: 30215866 ↗

    L5REVIEW_NARRATIVECited in: 13. Special Populations & Pregnancy
  109. [109]

    Neves JV, Olsson IA, Porto G et al.. “Hemochromatosis and pregnancy: iron stores in the Hfe-/- mouse are not reduced by multiple pregnancies.” American journal of physiology. Gastrointestinal and liver physiology (2010). PMID: 20110460 ↗

    L5OTHERCited in: 13. Special Populations & Pregnancy
  110. [110]

    Kröner PT, Mareth KF, Wijarnpreecha K et al.. “Hereditary hemochromatosis is associated with increased use of joint replacement surgery: Results of a nationwide analysis.” Seminars in arthritis and rheumatism (2019). PMID: 31818503 ↗

    L2OTHERCited in: 13. Special Populations & Pregnancy
  111. [111]

    Porto G, Brissot P, Swinkels DW et al.. “EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH).” European journal of human genetics : EJHG (2015). PMID: 26153218 ↗

    L1GUIDELINECited in: 14. Prevention, Screening & Surveillance

Revision History

All updates applied to this page

Loading revisions…