Chronic Liver Diseases


 Acute Hepatic Failure


 Pediatric Liver Diseases

Primary haemochromatosis

Most cases of haemochromatosis were inherited, a fact well known for most of the 20th century. However they were incorrectly assumed to depend on a single gene. The others which have been discovered are grouped together as "non-classical hereditary haemochromatosis", "non-HFE related hereditary haemochromatosis", or "non-HFE haemochromatosis".

Causes of Hereditary Hemochromatosis

Hereditary hemochromatosis is a genetic disorder caused by a mutation on a gene that regulates iron absorption, called HFE. Carriers don't necessarily have the condition themselves, but can pass the mutated gene on to their children. Two major mutations of HFE attributable to iron loading are C282Y and H63D People who inherit the HFE gene mutation from both parents are at the greatest risk of developing hemochromatosis.

Risk of Hereditary Hemochromatosis

Hereditary hemochromatosis can cause elevated liver iron concentration (LIC) and therefore iron overload and chronic liver disease. Not every individual who has the abnormal gene exhibits symptoms of the disease and has iron overload, elevated liver iron concentration (LIC) and finaly liver damage Liver damage due to high grade fibrosis. If hemochromatosis leads to fibrosis this is a risk factor for hepatocellular carcinoma (HCC)

Prevalence of Hemochromatosis

Hemochromatosis is common in countries with a population which is largely of Northern European origin. Hemochromatosis is one of the most common genetic disorders in the United States. An estimated 1 in 200 people of Northern European descent are homozygous for the most common hereditary hemochromatosis gene. Other sources state one in 240 to 300 Caucasians. 1 in every 8 to 10 people in the United States carries a single copy of this defective gene.Hemochromatosis is less common in African Americans, Asian Americans, Hispanic Americans, and American Indians.

Diagnosis of Hemochromatosis

Some people may test negative for the abnormal gene but still suffer from hemochromatosisDetermination of the magnitude of body iron stores will identify individuals who would benefit from phlebotomy therapy to prevent the risk of the chronic liver disease were the iron overload on the long term leads to liver damage.

Biopsy and/or regular monitoring for HCC may be recommended for patients who have had high LIC over a prolonged period.

Serum ferritin seems not to be a reliable indicator of body iron stores in hemochromatosis

Innovative methods use MRI ( to measure liver iron concentration (LIC) in hemochromatosis.Another new method uses superconducting quantum interference device (SQUID).

DescriptionMutation
haemochromatosis type 1: "classical"-haemochromatosisHFE
Haemochromatosis type 2A: juvenile haemochromatosishaemojuvelin ("HJV", also known as RGMc and HFE2
Haemochromatosis type 2B: juvenile haemochromatosishepcidin antimicrobial peptide (HAMP) or HFE2B
Haemochromatosis type 3transferrin receptor-2 (TFR2 or HFE3)
Haemochromatosis type 4 / African iron overloadferroportin (SLC11A3/SLC40A1)
Neonatal haemochromatosis(unknown)
Acaeruloplasminemia (very rare)caeruloplasmin
Congenital atransferrinaemia (very rare)transferrin
GRACILE syndrome (very rare)BCS1L

Complications in Hemochromatosis

Hepatic fibrosis is a complication of hereditary hemochromatosis and long time exposure to iron overload with elevated hepatic iron concentration can lead to cirrhosis.

Contact us regarding "Hemochromatosis"
or call Tilo Stolzke at +49 451 400 83 01 directly.

Studies and publications regarding Hereditary Hemochromatosis

  • St Pierre, TG, Clark, PR, Chua-Anusorn, W, et al. Non-invasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2004 (prepublished online July 15).
  • John K Olynyk MD, Timothy G St. Pierre PhD, Robert S Britton PhD, Elizabeth M Brunt MD and Bruce R Bacon Duration of Hepatic Iron Exposure Increases the Risk of Significant Fibrosis in Hereditary Hemochromatosis: A New Role for Magnetic Resonance ImagingMD The American Journal of Gastroenterology (2005) 100, 837-841; doi:10.1111/j.1572-0241.2005.41287.x
  • Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with -thalassemia. Blood. 2006;107: 3455-3462. (Prepublished online December 13, 2005, as DOI 10.1182/blood-2005-08-
  • Brink B, Disler P, Lynch S, Jacobs P, Charlton R, Bothwell T. Patterns of iron storage in dietary iron overload and idiopathic hemochromatosis. J Lab Clin Med. 1976;88: 725-731.
  • Butensky E, Fischer R, Hudes M, et al. Variability in hepatic iron concentration from percutaneous needle biopsy specimens in patients with transfusional hemosiderosis. Am J Clin Path. 2005;123: 146-152.
  • Fischer R, Piga A, Harmatz P, Nielsen P. Monitoring long-term efficacy of iron chelation treatment with biomagnetic liver susceptometry. Ann NY Acad Sci. 2005;1054: 350-357.
  • Roper-Bouchet M, Turlin B, Graham G, et al. Drying methods affect the wet:dry weight ratio of liver tissue samples and impact liver iron content measurements [abstract]. BioIron. 2005;107. Abstract P274.
  • Feder, JN, Gnirke, A, Thomas, W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996;13: 399-308.
  • Olynyk, JK, Cullen, DJ, Aquilia, S, et al. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999;341: 718-724.
  • Beutler, E, Felitti, VJ, Koziol, JA, et al. Penetrance of 845G-A (C282Y) HFE hereditary hemochromatosis mutation in the USA. Lancet 2002;359: 211-218.
  • Harrison, SA, Bacon, BR. Hereditary hemochromatosis: Update for 2003. J Hepatol 2003;38(Suppl 1):S14-S23.
  • Elmberg, M, Hultcrantz, R, Ekbom, A, et al. Cancer risk in patients with hereditary hemochromatosis and their first-degree relatives. Gastroenterology 2003;125: 1733-1741.
  • Olynyk, JK, Hagan, SE, Cullen, DJ, et al. Evolution of untreated hereditary hemochromatosis in the Busselton population: A 17-year study. Mayo Clin Proc 2004;79: 309-313.
  • Galhenage, SP, Viiala, CH, Olynyk, JK. Screening for hemochromatosis: Patients with liver disease, families, and populations. Curr Gastroenterol Rep 2004;6: 44-51.
  • Pietrangelo, A. Hereditary hemochromatosis: A new look at an old disease. N Engl J Med 2004;350: 2383-2397. Niederau, C, Fischer, R, Purschel, A, et al. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 1996;110: 1107-1119.
  • Guyader, D, Jacquilinet, C, Moirand, R, et al. Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis. Gastroenterology 1998;115: 929-936.
  • Bacon, BR, Olynyk, JK, Brunt, EM, et al. HFE genotypes in patients with hemochromatosis and in other liver diseases. Ann Int Med 1999;130: 953-962.
  • Morrison, ED, Brandhagen, DJ, Phatak, PD, et al. Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis. Ann Int Med 2003;138: 627-633.
  • Bassett, ML, Halliday, JW, Powell, LW. Value of hepatic iron measurements in early hemochromatosis and determination of the critical level associated with fibrosis. Hepatology 1986;6: 24-29.
  • Olynyk, J, Hall, P, Sallie, R, et al. Computerized measurement of iron in liver biopsies: Comparison with biochemical iron measurement. Hepatology 1990;12: 26-30.
  • Adams, P. Is there a threshold of hepatic iron concentration that leads to cirrhosis in C282Y hemochromatosis? Am J Gastroenterol 2001;96: 567-569.
  • Fletcher, LM, Dixon, JL, Purdie, DM, et al. Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis. Gastroenterology 2002;122: 281-289.
  • Bridle, KR, Crawford, DHG, Fletcher, LM, et al. Evidence for a sub-morphological inflammatory process in the liver in haemochromatosis. J Hepatol 2003;38: 521-525.
  • Sallie, RW, Reed, WD, Shilkin, KB. Confirmation of the efficacy of hepatic tissue iron index in differentiating genetic hemochromatosis from alcoholic liver disease complicated by alcoholic haemosiderosis. Gut 1991;32: 207-210.
  • Leicester, KL, Olynyk, JK, Brunt, EM, et al. CD14-positive hepatic monocytes/macrophages increase in hereditary hemochromatosis. Liver International (in press).? Torrance, JD, Bothwell, TH. Iron stores. Meth Hematol 1980;1: 90-115.
  • Olynyk, J, Williams, P, Fudge, A, et al. Fine needle aspiration liver biopsy for measurement of hepatic iron concentration. Hepatology 1992;15: 502-506.
  • Poynard, T, Bedossa, P, Opolon, P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997;349: 825-832.
  • Di Bisceglie, AM. Natural history of hepatitis C: Its impact on clinical management. Hepatology 2000;31: 1014-1018.
  • Asberg, A, Hveem, K, Thorstensen, K, et al. Screening for hemochromatosis: High prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastroenterol 2001;10: 1108-1115.
  • McCune, CA, Al-Jader, LN, May, A, et al. Hereditary haemochromatosis: Only 1% of adult HFE C282Y homozygotes in South Wales have a clinical diagnosis of iron overload. Hum Genet 2002;111: 538-543.
  • Andersen, RV, Tybjaerg-Hansen, A, Appleyeard, M, et al. Hemochromatosis mutations in the general population: Iron overload progression rate. Blood 2004;103: 2914-2919.
  • Beaton, M, Guyader, D, Deugnier, Y, et al. Noninvasive prediction of cirrhosis in C282Y-linked hemochromatosis. Hepatology 2002;36: 673-678.
Hereditary Hemochromatosis