Medscape is available in 5 Language Editions – Choose your Edition here.


Hemochromatosis Treatment & Management

  • Author: Andrea Duchini, MD; Chief Editor: Julian Katz, MD  more...
Updated: Jan 02, 2016

Approach Considerations

Despite advances in the molecular understanding of hemochromatosis and the impact of C282Y on diagnosis, treatment remains simple, inexpensive, and safe.

The goal of therapy in patients with iron overload disorders is to remove the iron before it can produce irreversible parenchymal damage.[8]  This is achieved via chelation therapy or venesection, depending on the underlying cause.[88] Because a normal life span can be expected if iron reduction is initiated before the development of cirrhosis, clinical suspicion and early diagnosis are essential.

The tetrad of cirrhosis, diabetes mellitus, hyperpigmentation of the skin, and cardiac failure may be evident in only a minority of patients.[89] Any patient admitted to the hospital with an isolated case of asthenia or with arthralgia or hypertransaminasemia should be examined by means of transferrin-saturation testing.

Cardiac manifestations of hereditary hemochromatosis could have sudden onset and could be poorly responsive to therapy. The hemochromatic etiology of the cardiomyopathy should be identified to ensure appropriate treatment.

Admission to the intensive care unit (ICU) may be warranted for patients who develop hepatic, cardiac, and infectious complications. Indications for inpatient care, preferably in an ICU, include the following:

  • Gastroesophageal bleeding
  • Hepatic encephalopathy
  • Sepsis
  • Congestive heart failure
  • Arrhythmias

Transfer considerations

In case of end-stage liver disease that is refractory to all methods of medical treatment, transferring the patient to a facility experienced in liver transplantation is preferable.

When the diagnosis of hepatocellular carcinoma is being considered or if the diagnosis is confirmed, transfer the patient to a cancer institution.


Surgical Intervention

Surgical procedures are used to treat 2 important complications: end-stage liver disease and severe arthropathy.

When end-stage liver disease progresses despite iron-reduction therapy, orthotopic liver transplantation is the only therapeutic option.[9] Another indication for liver transplantation is the development of hepatocellular carcinoma.

Careful patient selection is advised for liver transplantation to treat patients with hepatocellular carcinoma. Particularly, these patients should have a single tumor of 5 cm or smaller in diameter. If multiple tumors are present, the acceptable number is 3 tumors or less, smaller than 3 cm. The 4-year survival rate can be approximately 90% if these criteria are respected.

Surgical arthroplasty is considered if joint destruction becomes severe despite medical therapy.



Once diagnosed, hemochromatosis is treated by phlebotomy to rid the body of excess iron and to maintain normal iron stores. Phlebotomy remains the sole recommended treatment for hereditary hemochromatosis and should be undertaken in a case-specific manner.

The AASLD guidelines state hereditary hemochromotosis patients who have evidence of iron overload are “strongly encouraged” to receive phlebotomy regularly until iron stores are depleted. The regular phlebotomies should continue for life, and the frequency of maintenance therapy should be based on serum ferritin levels.[7]

In the induction phase, weekly phlebotomy is made, with blood removal of 7 mL/kg per phlebotomy (not to exceed 550 mL per phlebotomy).[90] The efficacy of treatment is controlled by ferritin level evaluation in plasma once monthly until the values remain above the upper limits of normal (300 mcg/L in men; 200 mcg/L in women). The hemoglobin level must be checked before each procedure; the reference value is 12-13g/dL (120-130g/L).[90] Subsequently, evaluation of ferritin concentration should be performed bimonthly until its level is reduced below 50 mcg/L.

In the maintenance phase, the phlebotomy should be performed every 2-4 months. The interval between procedures is determined by the level of ferritin, which should be lower than 50 mcg/mL.[90, 91]

In a retrospective analysis of 12 paired patients from the Netherlands with hereditary hemochromatosis homozygous for the C282Y mutation, those who received proton pump inhibitors (PPIs) had a significant reduction in the frequency of median number of phlebotomies (0.50) compared with before the administration of PPIs (3.17), and those who received PPIs for at least 2 years required signifcantly fewer phlebotomies (1.25) than those in the paired group before they began taking PPIs (3.17).[92]  Moreover, there were a significantly lower number of phlebotomies in the paired group after initiation of PPIs compared to that of patients who never received PPIs.

One study showed that phlebotomy therapy can reduce liver fibrosis, and the effects of therapy are dependent on the stage of the disease.[93] Among individuals with biopsy results positive for liver fibrosis, phlebotomy was associated with an improvement of 13-50%, with the greatest improvement among individuals with the least degree of liver fibrosis. Individuals served as their own controls, and improvement was based on qualitative histologic features. When liver cirrhosis is present and in its early stages, therapeutic phlebotomy appears to control or slow the progression of liver disease. In addition, the results of phlebotomy therapy can be predicted by the simple biochemical tests.[93]


Phlebotomy is generally a safe and efficient method of iron removal. Encourage patients to have weekly therapeutic phlebotomy of 500 mL of whole blood (equivalent to approximately 200-250 mg of iron).[94] Some patients can tolerate twice-weekly phlebotomy, but this regimen is tedious and often inconvenient. Therapeutic phlebotomy should be performed until iron-limited erythropoiesis develops, identified by failure of the hemoglobin level and/or hematocrit to recover before the next phlebotomy. It should be continued until transferrin saturation is less than 50% and serum ferritin levels are less than 50 ng/mL, preferably 20 ng/mL.

Most patients require maintenance phlebotomy in which 1 unit of blood is removed every 2-3 months. Therapeutic phlebotomy may improve or even cure some of the manifestations and complications of the disease, such as fatigue, elevated liver enzymes, hepatomegaly, abdominal pain, arthralgias, and hyperpigmentation. Other complications usually show little or no change after phlebotomy.

Avoid excessive phlebotomy and the risk of hypovolemia and dehydration.


Chelation Therapy

In patients with hemochromatosis and heart disease, anemia, or poor venous access, treatment with iron chelation agents is recommended. The therapeutic perspectives comprise compounds inhibiting intestinal absorption of iron, chelators of iron, hepcidin, or ferroportin supplementation. In disease caused by hepcidin deficiency, protein supplementation with hepcidin is advised.


Deferasirox (Exjade) is the oral iron chelator that should be taken once daily as an adjunct to phlebotomies or instead of phlebotomy in patients in whom these procedures are poorly tolerated. Deferasirox is very efficacious in liver iron removal. During treatment with deferasirox, kidney function should be controlled.[95]

In a study that evaluated the effects of deferasirox in Hjv-/- mice (knockout animals lacking hemojuvelin [HJV]; ie, an experimental model of hereditary hemochromatosis), a dose of 100 mg/kg markedly reduced the iron level in the liver and heart. However, in the pancreas, deferasirox was less effective, and the splenic iron count was not influenced.[96] Deferasirox was administered once daily 5 times a week.


The family of dendrimers, iron-selective chelators, have been synthesized.[97] Dendrimers terminated with hydroxypiridinone have high affinity to iron and reduce its absorption in the rat intestine. Therefore, the application of the dendrimers in the treatment of iron overload diseases is considered.

In experiments performed on rats compared the protective effect of 2 iron chelators, deferoxamine and deferiprone, on iron overload in the heart, deferiprone was found to reduce histopathologic changes in the heart of rats chronically loaded with iron.[98] The 2 compounds were administered individually or in combination with vitamin C (vitamin C was used as the antioxidative compound aimed at preventing heart oxidative injury). Additional administration of vitamin C improved histopathologic changes and biochemical markers in the heart.[98]

Juvenile hemochromatosis

The first patient affected by juvenile hemochromatosis was successfully treated with chelation therapy. Because of severe congestive heart failure, phlebotomy was contradicted. Simultaneous administration of deferoxamine and deferiprone reduced the myocardial dysfunction and improved the clinical status of that patient.


Patients affected with anemia cannot be treated with phlebotomy. Thus, application of iron chelation agents (eg, deferoxamine, deferiprone, deferasirox) is recommended.[99]

Deferoxamine is administered intravenously or subcutaneously at doses ranging from 25 to 40 mg/kg. Intravenous infusion is usually 8-10 hours in duration and is repeated 5 nights per week. Similar effects can be obtained with subcutaneous bolus injections administered twice daily. The main adverse effects are inflammatory reactions at the sites of injection, visual and auditory disturbances, bone growth disturbances, and allergic reactions, including anaphylaxis.

Deferiprone is given orally in 3 divided doses of 75 mg/kg/d. Agranulocytosis, neutropenia, arthralgia, gastrointestinal reactions, and elevation of liver enzyme levels are the main adverse effects. Cardiac iron overload is better reduced by deferiprone than deferoxamine.

Deferasirox is an oral chelation agent, administered at 10-30 mg/kg. Deferasirox adverse effects can include elevation of the creatinine level, skin exanthem, diarrhea, and visual and auditory disturbances.


Dietary Considerations and Prevention

Dietary factors may influence the phenotypic expression of hemochromatosis. Some modulate absorption of iron and may affect the variability of phenotypic penetrance. However dietary changes intended to minimize or eliminate iron ingestion are usually unnecessary and are often not feasible.

Patients should not consume foods that contain large concentrations of bioavailable iron, such as red meats and organ meats. In addition, they should not use iron supplements, including multivitamins with iron. In addition, vitamin C supplements should be avoided. Substances in foods and drinks, including tannates (in tea), phytates, oxalates, calcium, and phosphates, can bind iron and inhibit its absorption.

Alcohol abuse may accelerate disease progression. Ethanol sometimes increases iron absorption, and certain alcoholic drinks, especially red wine, contain relatively high concentrations of iron. Activity of hydroxyl free radicals is elevated by iron-containing diets combined with alcohol intake, and this is implicated in hepatocarcinogenesis.[100] Ingestion of 30 g or more of ethanol daily potentiates hepatic injury due to iron overload and increases the relative risk for primary liver cancer in persons with cirrhosis. Patients with evidence of hepatic injury should consume little or no ethanol. Other patients should consume ethanol in moderation.

Studies performed on healthy subjects living in the Spanish-Mediterranean coast showed that some genotypes (C282Y heterozygote, H63D heterozygote, and homozygote, as well as H63D/S63C compound heterozygote) together with alcohol and iron intake increased indicators of iron status; however, calcium intake decreased them.[101] These effects were not observed in S63C heterozygotes.[101]

Vitamin C (ascorbic acid) increases intestinal absorption of inorganic iron. No reason exists to discourage patients from eating fresh fruits and vegetables containing vitamin C, but advising them to limit ingestion of vitamin C in supplements to 500 mg/d is prudent. Use mineral supplements for specific deficiencies only.

Seafood from potentially contaminated waters must be cooked thoroughly. Raw or improperly cooked shellfish is sometimes contaminated with Vibrio vulnificus and can cause sepsis in patients with hemochromatosis.



Promptly refer patients to a gastroenterologist and a liver transplant center in case of end-stage liver disease, especially if it is refractory to treatment. Most often, a gastroenterologist is required to confirm the diagnosis by liver biopsy and to assist in the management of end-stage liver diseases. A surgeon specializing in liver transplantation may be needed in cases of highly advanced liver disease.

In addition, due to the multiorgan nature of the disease and the injury or damage to many intrinsic systems, care and treatment of patients with hemochromatosis require the collaboration of other physicians in different medical or surgical specialties, such as the following:

  • An endocrinologist is helpful in treating patients with diabetes mellitus or other endocrine complications, such as thyroid and gonadal dysfunction
  • A cardiologist assists in the management of severe congestive heart failure and other cardiac complications, such as arrhythmias
  • An infectious disease specialist can treat patients with sepsis and can also choose the appropriate antibiotic therapy for rare infectious complications
  • A rheumatologist or an orthopedist is required for the management of joint complications.
  • A geneticist is valuable for family screening in all first-degree relatives of newly diagnosed individuals

Long-Term Monitoring

The patient should have a primary care provider who can coordinate treatment with the other specialists involved. Physicians should be aware of the possibility of hereditary hemochromatosis, and they should perform diagnostic tests when hereditary hemochromatosis is suspected. Moreover, patient education as to the importance of early diagnosis and lifelong treatment is essential for symptom-free life.

Regular monitoring of hematocrit, hemoglobin, and serum ferritin levels is necessary in patients undergoing phlebotomy. Genetic testing for hereditary hemochromatosis should also be performed in family members of patients with hereditary hemochromatosis.

Continuous observation of patients with hereditary hemochromatosis regarding the potential complications of the disease is recommended. Regular follow-up visits should be scheduled with the gastroenterologist. Others, such as a cardiologist, an endocrinologist, or a hematologist, may be needed for serial diagnostic and therapeutic intervention. Quarterly visits with healthcare providers may be necessary depending on the severity of the symptoms or complications.

Hepatocellular carcinoma is one of the most serious complications of hemochromatosis. Most hepatologists recommend periodic screening with serum alpha-fetoprotein (AFP) every 6 months in patients with cirrhosis. The most cost-effective imaging test used to supplement serum AFP screening is ultrasonography; the sensitivity is approximately 80% when serum AFP and ultrasonograms are combined for the screening of hepatocellular carcinoma.

Contributor Information and Disclosures

Andrea Duchini, MD Associate Professor of Medicine and Surgery, Director of Hepatology, University of Texas Medical Branch School of Medicine; Medical Director of Liver Transplantation, Department of Surgery, University of Texas Medical Branch School of Medicine

Andrea Duchini, MD is a member of the following medical societies: American College of Physicians, International Liver Transplantation Society, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.


David M Klachko, MD, MEd Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Missouri-Columbia School of Medicine

David M Klachko, MD, MEd is a member of the following medical societies: Alpha Omega Alpha, Missouri State Medical Association, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, Endocrine Society, Sigma Xi

Disclosure: Nothing to disclose.

Hady E Sfeir, MD Clinical Assistant Professor of Medicine, Department of Internal Medicine, OSF St Francis Medical Center

Hady E Sfeir, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, Physicians for Social Responsibility

Disclosure: Nothing to disclose.


Vivek V Gumaste, MD Associate Professor of Medicine, Mount Sinai School of Medicine of New York University; Adjunct Clinical Assistant, Mount Sinai Hospital; Director, Division of Gastroenterology, City Hospital Center

Vivek V Gumaste, MD is a member of the following medical societies: American College of Gastroenterology and American Gastroenterological Association

Disclosure: Nothing to disclose.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. Fleming RE, Sly WS. Mechanisms of iron accumulation in hereditary hemochromatosis. Annu Rev Physiol. 2002. 64:663-80. [Medline].

  2. McCullen MA, Crawford DH, Hickman PE. Screening for hemochromatosis. Clin Chim Acta. 2002 Jan. 315(1-2):169-86. [Medline].

  3. O'Reilly FM, Darby C, Fogarty J, Tormey W, Kay EW, Leader M, et al. Screening of patients with iron overload to identify hemochromatosis and porphyria cutanea tarda. Arch Dermatol. 1997 Sep. 133(9):1098-101. [Medline].

  4. Centers for Disease Control and Prevention (CDC). Iron overload and hemochromatosis. May 2006. [Full Text].

  5. Valenti L, Varenna M, Fracanzani AL, Rossi V, Fargion S, Sinigaglia L. Association between iron overload and osteoporosis in patients with hereditary hemochromatosis. Osteoporos Int. 2009 Apr. 20(4):549-55. [Medline].

  6. Swinkels DW, Jorna AT, Raymakers RA. Synopsis of the Dutch multidisciplinary guideline for the diagnosis and treatment of hereditary haemochromatosis. Neth J Med. 2007 Dec. 65(11):452-5. [Medline].

  7. [Guideline] Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011 Jul. 54(1):328-43. [Medline]. [Full Text].

  8. Worwood M. Pathogenesis and management of haemochromatosis. Br J Haematol. 1999 Apr. 105 Suppl 1:16-8. [Medline].

  9. Khanna A, Jain A, Eghtesad B, et al. Liver transplantation for metabolic liver diseases. Surg Clin North Am. 1999 Feb. 79(1):153-62, ix. [Medline].

  10. Seravalle G, Piperno A, Mariani R, et al. Alterations in sympathetic nerve traffic in genetic haemochromatosis before and after iron depletion therapy: a microneurographic study. Eur Heart J. 2015 Dec 28. [Medline].

  11. Gattermann N. The treatment of secondary hemochromatosis. Dtsch Arztebl Int. 2009 Jul. 106(30):499-504, I. [Medline]. [Full Text].

  12. Janssen MC, Swinkels DW. Hereditary haemochromatosis. Best Pract Res Clin Gastroenterol. 2009. 23(2):171-83. [Medline].

  13. Galbraith R. Heme oxygenase: who needs it?. Proc Soc Exp Biol Med. 1999 Dec. 222(3):299-305. [Medline].

  14. Wang L, Johnson EE, Shi HN, Walker WA, Wessling-Resnick M, Cherayil BJ. Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation. J Immunol. 2008 Aug 15. 181(4):2723-31. [Medline]. [Full Text].

  15. Conrad ME, Umbreit JN, Moore EG. Iron absorption and transport. Am J Med Sci. 1999 Oct. 318(4):213-29. [Medline].

  16. Parkkila S, Niemelä O, Britton RS, Fleming RE, Waheed A, Bacon BR, et al. Molecular aspects of iron absorption and HFE expression. Gastroenterology. 2001 Dec. 121(6):1489-96. [Medline].

  17. Rolfs A, Bonkovsky HL, Kohlroser JG, et al. Intestinal expression of genes involved in iron absorption in humans. Am J Physiol Gastrointest Liver Physiol. 2002 Apr. 282(4):G598-607. [Medline].

  18. Papanikolaou G, Samuels ME, Ludwig EH, et al. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet. 2004 Jan. 36(1):77-82. [Medline].

  19. Papanikolaou G, Politou M, Roetto A, Bosio S, Sakelaropoulos N, Camaschella C, et al. Linkage to chromosome 1q in Greek families with juvenile hemochromatosis. Blood Cells Mol Dis. 2001 Jul-Aug. 27(4):744-9. [Medline].

  20. Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006 May. 38(5):531-9. [Medline].

  21. Park CH, Valore EV, Waring AJ, et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001 Mar 16. 276(11):7806-10. [Medline].

  22. Fleming RE, Britton RS, Waheed A, et al. Pathogenesis of hereditary hemochromatosis. Clin Liver Dis. 2004 Nov. 8(4):755-73, vii. [Medline].

  23. Montosi G, Donovan A, Totaro A, Garuti C, Pignatti E, Cassanelli S, et al. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest. 2001 Aug. 108(4):619-23. [Medline]. [Full Text].

  24. Himmelmann A, Fehr J. Cloning of the hereditary hemochromatosis gene: implications for pathogenesis, diagnosis, and screening. J Lab Clin Med. 1999 Mar. 133(3):229-36. [Medline].

  25. Bittencourt PL, Marin ML, Couto CA, et al. Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis. Clinics (Sao Paulo). 2009. 64(9):837-41. [Medline]. [Full Text].

  26. Ramrakhiani S, Bacon BR. Hemochromatosis: advances in molecular genetics and clinical diagnosis. J Clin Gastroenterol. 1998 Jul. 27(1):41-6. [Medline].

  27. Gochee PA, Powell LW, Cullen DJ, et al. A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation. Gastroenterology. 2002 Mar. 122(3):646-51. [Medline].

  28. Gurrin LC, Bertalli NA, Dalton GW, Osborne NJ, Constantine CC, McLaren CE, et al. HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity. Hepatology. 2009 Jul. 50(1):94-101. [Medline].

  29. Wallace DF, Walker AP, Pietrangelo A, et al. Frequency of the S65C mutation of HFE and iron overload in 309 subjects heterozygous for C282Y. J Hepatol. 2002 Apr. 36(4):474-9. [Medline].

  30. Solanas-Barca M, Mateo-Gallego R, Calmarza P, et al. Mutations in HFE causing hemochromatosis are associated with primary hypertriglyceridemia. J Clin Endocrinol Metab. 2009 Nov. 94(11):4391-7. [Medline].

  31. Bridle KR, Frazer DM, Wilkins SJ, et al. Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet. 2003 Feb 22. 361(9358):669-73. [Medline].

  32. Muckenthaler M, Roy CN, Custodio AO, et al. Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis. Nat Genet. 2003 May. 34(1):102-7. [Medline].

  33. Nemeth E, Roetto A, Garozzo G, et al. Hepcidin is decreased in TFR2 hemochromatosis. Blood. 2005 Feb 15. 105(4):1803-6. [Medline].

  34. Gehrke SG, Kulaksiz H, Herrmann T, et al. Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron. Blood. 2003 Jul 1. 102(1):371-6. [Medline].

  35. Hattori A, Wakusawa S, Hayashi H, et al. AVAQ 594-597 deletion of the TfR2 gene in a Japanese family with hemochromatosis. Hepatol Res. 2003 Jun. 26(2):154-156. [Medline].

  36. Kawabata H, Fleming RE, Gui D, et al. Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis. Blood. 2005 Jan 1. 105(1):376-81. [Medline].

  37. Powell LW. Diagnosis of hemochromatosis. Semin Gastrointest Dis. 2002 Apr. 13(2):80-8. [Medline].

  38. Steinberg KK, Cogswell ME, Chang JC, Caudill SP, McQuillan GM, Bowman BA, et al. Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States. JAMA. 2001 May 2. 285(17):2216-22. [Medline].

  39. Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ. Global prevalence of putative haemochromatosis mutations. J Med Genet. 1997 Apr. 34(4):275-8. [Medline]. [Full Text].

  40. Byrnes V, Ryan E, Barrett S, Kenny P, Mayne P, Crowe J. Genetic hemochromatosis, a Celtic disease: is it now time for population screening?. Genet Test. 2001 Summer. 5(2):127-30. [Medline].

  41. Wood MJ, Skoien R, Powell LW. The global burden of iron overload. Hepatol Int. 2009 Jul 29. [Medline]. [Full Text].

  42. Gochee PA, Powell LW. What's new in hemochromatosis. Curr Opin Hematol. 2001 Mar. 8(2):98-104. [Medline].

  43. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med. 1999 Sep 2. 341(10):718-24. [Medline].

  44. Gehrke SG, Pietrangelo A, Kascák M, Braner A, Eisold M, Kulaksiz H, et al. HJV gene mutations in European patients with juvenile hemochromatosis. Clin Genet. 2005 May. 67(5):425-8. [Medline].

  45. Adams PC, Barton JC. Haemochromatosis. Lancet. 2007 Dec 1. 370(9602):1855-60. [Medline].

  46. Adams PC, Reboussin DM, Barton JC, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med. 2005 Apr 28. 352(17):1769-78. [Medline].

  47. Gleeson F, Ryan E, Barrett S, et al. Clinical expression of haemochromatosis in Irish C282Y homozygotes identified through family screening. Eur J Gastroenterol Hepatol. 2004 Sep. 16(9):859-63. [Medline].

  48. Acton RT, Barton JC, Bell DS, Go RC, Roseman JM. HFE mutations in African-American women with non-insulin-dependent diabetes mellitus. Ethn Dis. 2001 Fall. 11(4):578-84. [Medline].

  49. Allen KJ, Gurrin LC, Constantine CC, et al. Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med. 2008 Jan 17. 358(3):221-30. [Medline].

  50. Barton JC, Wiener HW, Acton RT, et al. HLA haplotype A*03-B*07 in hemochromatosis probands with HFE C282Y homozygosity: frequency disparity in men and women and lack of association with severity of iron overload. Blood Cells Mol Dis. 2005 Jan-Feb. 34(1):38-47. [Medline].

  51. Rivers CA, Barton JC, Gordeuk VR, et al. Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Blood Cells Mol Dis. 2007 May-Jun. 38(3):247-52. [Medline].

  52. Bulaj ZJ, Ajioka RS, Phillips JD, LaSalle BA, Jorde LB, Griffen LM, et al. Disease-related conditions in relatives of patients with hemochromatosis. N Engl J Med. 2000 Nov 23. 343(21):1529-35. [Medline].

  53. Moirand R, Adams PC, Bicheler V, Brissot P, Deugnier Y. Clinical features of genetic hemochromatosis in women compared with men. Ann Intern Med. 1997 Jul 15. 127(2):105-10. [Medline].

  54. Niederau C, Strohmeyer G, Stremmel W. Epidemiology, clinical spectrum and prognosis of hemochromatosis. Adv Exp Med Biol. 1994. 356:293-302. [Medline].

  55. Milman N, Pedersen P, á Steig T, Byg KE, Graudal N, Fenger K. Clinically overt hereditary hemochromatosis in Denmark 1948-1985: epidemiology, factors of significance for long-term survival, and causes of death in 179 patients. Ann Hematol. 2001 Dec. 80(12):737-44. [Medline].

  56. Yang Q, McDonnell SM, Khoury MJ, Cono J, Parrish RG. Hemochromatosis-associated mortality in the United States from 1979 to 1992: an analysis of Multiple-Cause Mortality Data. Ann Intern Med. 1998 Dec 1. 129(11):946-53. [Medline].

  57. Bathum L, Christiansen L, Nybo H, Ranberg KA, Gaist D, Jeune B, et al. Association of mutations in the hemochromatosis gene with shorter life expectancy. Arch Intern Med. 2001 Nov 12. 161(20):2441-4. [Medline].

  58. Bothwell TH, MacPhail AP. Hereditary hemochromatosis: etiologic, pathologic, and clinical aspects. Semin Hematol. 1998 Jan. 35(1):55-71. [Medline].

  59. Smith BC, Gorve J, Guzail MA, Day CP, Daly AK, Burt AD, et al. Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C. Hepatology. 1998 Jun. 27(6):1695-9. [Medline].

  60. Martinelli AL, Franco RF, Villanova MG, Figueiredo JF, Secaf M, Tavella MH, et al. Are haemochromatosis mutations related to the severity of liver disease in hepatitis C virus infection?. Acta Haematol. 2000. 102(3):152-6. [Medline].

  61. George DK, Goldwurm S, MacDonald GA, Cowley LL, Walker NI, Ward PJ, et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology. 1998 Feb. 114(2):311-8. [Medline].

  62. Bonkovsky HL, Jawaid Q, Tortorelli K, LeClair P, Cobb J, Lambrecht RW, et al. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol. 1999 Sep. 31(3):421-9. [Medline].

  63. O'Sullivan EP, McDermott JH, Murphy MS, Sen S, Walsh CH. Declining prevalence of diabetes mellitus in hereditary haemochromatosis--the result of earlier diagnosis. Diabetes Res Clin Pract. 2008 Sep. 81(3):316-20. [Medline].

  64. Bailey EJ, Gardner AB. Hemochromatosis of the foot and ankle. Report of three cases and review of the literature. Clin Orthop Relat Res. 1998 Apr. 108-15. [Medline].

  65. Ellervik C, Tybjaerg-Hansen A, Grande P, Appleyard M, Nordestgaard BG. Hereditary hemochromatosis and risk of ischemic heart disease: a prospective study and a case-control study. Circulation. 2005 Jul 12. 112(2):185-93. [Medline].

  66. Wetterhall SF, Cogswell ME, Kowdley KV. Public health surveillance for hereditary hemochromatosis. Ann Intern Med. 1998 Dec 1. 129(11):980-6. [Medline].

  67. Cogswell ME, McDonnell SM, Khoury MJ, et al. Iron overload, public health, and genetics: evaluating the evidence for hemochromatosis screening. Ann Intern Med. 1998 Dec 1. 129(11):971-9. [Medline].

  68. Beutler E, Felitti VJ, Koziol JA, et al. Penetrance of 845G--> A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet. 2002 Jan 19. 359(9302):211-8. [Medline].

  69. Wojcik JP, Speechley MR, Kertesz AE, et al. Natural history of C282Y homozygotes for hemochromatosis. Can J Gastroenterol. 2002 May. 16(5):297-302. [Medline].

  70. Powell LW, Dixon JL, Ramm GA, et al. Screening for hemochromatosis in asymptomatic subjects with or without a family history. Arch Intern Med. 2006 Feb 13. 166(3):294-301. [Medline].

  71. McDonnell SM, Phatak PD, Felitti V, et al. Screening for hemochromatosis in primary care settings. Ann Intern Med. 1998 Dec 1. 129(11):962-70. [Medline].

  72. Edwards CQ, Griffen LM, Ajioka RS, et al. Screening for hemochromatosis: phenotype versus genotype. Semin Hematol. 1998 Jan. 35(1):72-6. [Medline].

  73. Adams PC, Kertesz AE, McLaren CE, Barr R, Bamford A, Chakrabarti S. Population screening for hemochromatosis: a comparison of unbound iron-binding capacity, transferrin saturation, and C282Y genotyping in 5,211 voluntary blood donors. Hepatology. 2000 May. 31(5):1160-4. [Medline].

  74. Lyon E, Frank EL. Hereditary hemochromatosis since discovery of the HFE gene. Clin Chem. 2001. 47(7):1147-56. [Medline].

  75. Adams PC. Role of genetic testing and liver biopsy in the diagnosis of hemochromatosis. Curr Gastroenterol Rep. 1999 Feb-Mar. 1(1):27-9. [Medline].

  76. Barton JC, Acton RT. Hemochromatosis and Vibrio vulnificus wound infections. J Clin Gastroenterol. 2009 Apr 3. [Medline].

  77. Brittenham GM, Weiss G, Brissot P, Lainé F, Guillygomarc'h A, Guyader D, et al. Clinical Consequences of New Insights in the Pathophysiology of Disorders of Iron and Heme Metabolism. Hematology Am Soc Hematol Educ Program. 2000. 39-50. [Medline].

  78. Qaseem A, Aronson M, Fitterman N, et al. Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2005 Oct 4. 143(7):517-21. [Medline].

  79. Bacon BR. Hemochromatosis: diagnosis and management. Gastroenterology. 2001 Feb. 120(3):718-25. [Medline].

  80. Pawlowski M, Latute F, Bardou-Jacquet E, et al. Portable hemoglobinometer is a reliable technology for the follow-up of venesections tolerance in hemochromatosis. Clin Res Hepatol Gastroenterol. 2015 Oct. 39 (5):570-5. [Medline].

  81. Brandhagen DJ, Fairbanks VF, Baldus W. Recognition and management of hereditary hemochromatosis. Am Fam Physician. 2002 Mar 1. 65(5):853-60. [Medline].

  82. Morrison ED, Brandhagen DJ, Phatak PD, et al. Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis. Ann Intern Med. 2003 Apr 15. 138(8):627-33. [Medline].

  83. Powell LW, Subramaniam VN, Yapp TR. Haemochromatosis in the new millennium. J Hepatol. 2000. 32(1 Suppl):48-62. [Medline].

  84. McDonnell SM, Witte DL, Cogswell ME, et al. Strategies to increase detection of hemochromatosis. Ann Intern Med. 1998 Dec 1. 129(11):987-92. [Medline].

  85. Powell LW, George DK, McDonnell SM, et al. Diagnosis of hemochromatosis. Ann Intern Med. 1998 Dec 1. 129(11):925-31. [Medline].

  86. Turlin B, Deugnier Y. Evaluation and interpretation of iron in the liver. Semin Diagn Pathol. 1998 Nov. 15(4):237-45. [Medline].

  87. Morcos M, Dubois S, Bralet MP, Belghiti J, Degott C, Terris B. Primary liver carcinoma in genetic hemochromatosis reveals a broad histologic spectrum. Am J Clin Pathol. 2001 Nov. 116(5):738-43. [Medline].

  88. Brissot P. Optimizing the diagnosis and the treatment of iron overload diseases. Expert Rev Gastroenterol Hepatol. 2015 Dec 16. 1-12. [Medline].

  89. Durupt S, Durieu I, Nové-Josserand R, Bencharif L, Rousset H, Vital Durand D. [Hereditary hemochromatosis]. Rev Med Interne. 2000 Nov. 21(11):961-71. [Medline].

  90. Bismuth M, Peynaud-Debayle E, for the Haute Autorite de Sante (HAS) guidelines department. Management of patients with HFE-related haemochromatosis (type 1 haemochromatosis) (July 2005). Available at Accessed: June 10, 2011.

  91. Brissot P, Troadec MB, Bardou-Jacquet E, Le Lan C, Jouanolle AM, Deugnier Y, et al. Current approach to hemochromatosis. Blood Rev. 2008 Jul. 22(4):195-210. [Medline].

  92. van Aerts RM, van Deursen CT, Koek GH. Proton pump inhibitors reduce the frequency of phlebotomy in patients with hereditary hemochromatosis. Clin Gastroenterol Hepatol. 2016 Jan. 14 (1):147-52. [Medline].

  93. Falize L, Guillygomarc'h A, Perrin M, Lainé F, Guyader D, Brissot P, et al. Reversibility of hepatic fibrosis in treated genetic hemochromatosis: a study of 36 cases. Hepatology. 2006 Aug. 44(2):472-7. [Medline].

  94. Barton JC, McDonnell SM, Adams PC, et al. Management of hemochromatosis. Hemochromatosis Management Working Group. Ann Intern Med. 1998 Dec 1. 129(11):932-9. [Medline].

  95. Nick H. Iron chelation, quo vadis?. Curr Opin Chem Biol. 2007 Aug. 11(4):419-23. [Medline].

  96. Nick H, Allegrini PR, Fozard L, Junker U, Rojkjaer L, Salie R, et al. Deferasirox reduces iron overload in a murine model of juvenile hemochromatosis. Exp Biol Med (Maywood). 2009 May. 234(5):492-503. [Medline].

  97. Zhou T, Neubert H, Liu DY, Liu ZD, Ma YM, Kong XL, et al. Iron binding dendrimers: a novel approach for the treatment of haemochromatosis. J Med Chem. 2006 Jul 13. 49(14):4171-82. [Medline].

  98. Emara AM, El Kelany RS, Moustafa KA. Comparative study of the protective effect between deferoxamine and deferiprone on chronic iron overload induced cardiotoxicity in rats. Hum Exp Toxicol. 2006 Jul. 25(7):375-85. [Medline].

  99. Hazin R, Abu-Rajab Tamimi TI, Abuzetun JY, Zein NN. Recognizing and treating cutaneous signs of liver disease. Cleve Clin J Med. 2009 Oct. 76(10):599-606. [Medline].

  100. Asare GA, Bronz M, Naidoo V, Kew MC. Synergistic interaction between excess hepatic iron and alcohol ingestion in hepatic mutagenesis. Toxicology. 2008 Dec 5. 254(1-2):11-8. [Medline].

  101. Aranda N, Viteri FE, Montserrat C, Arija V. Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain. Ann Hematol. 2010 Aug. 89(8):767-73. [Medline]. [Full Text].

  102. Barton JC. Chelation therapy for iron overload. Curr Gastroenterol Rep. 2007 Mar. 9(1):74-82. [Medline].

  103. Imran F, Phatak P. Pharmacoeconomic benefits of deferasirox in the management of iron overload syndromes. Expert Rev Pharmacoecon Outcomes Res. 2009 Aug. 9(4):297-304. [Medline].

  104. Frenzen K, Schäfer C, Keyßer G. Erosive and inflammatory joint changes in hereditary hemochromatosis arthropathy detected by low-field magnetic resonance imaging. Rheumatol Int. 2013 Feb 12. [Medline].

  105. Lucotte G, Champenois T, Sémonin O. A rare case of a patient heterozygous for the hemochromatosis mutation C282Y and homozygous for H63D. Blood Cells Mol Dis. 2001 Sep-Oct. 27(5):892-3. [Medline].

  106. Barton JC, Edwards CQ, Acton RT. HFE gene: Structure, function, mutations, and associated iron abnormalities. Gene. 2015 Dec 15. 574 (2):179-92. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.