AASLD develops evidence-based practice guidelines and practice guidances which are updated regularly by a multi-disciplinary panel of experts, including hepatologists, and include recommendations of preferred approaches to the diagnostic, therapeutic, and preventive aspects of care.
Management of Hemochromatosis
Diagnosis and Management of Hemochromatosis [updated July 2011]
Hereditary hemochromatosis (HH) remains the most common, identified, genetic disorder in Caucasians. Although its geographic distribution is worldwide, it is seen most commonly in populations of northern European origin, particularly Nordic or Celtic ancestry, in which it occurs with a prevalence of approximately 1 per 220-250 individuals. The pathophysiologic predisposition to increased, inappropriate absorption of dietary iron may lead to the development of life-threatening complications of cirrhosis, hepatocellular carcinoma (HCC), diabetes, and heart disease. The principal HFE gene defect was first described in 1996, and is a G-to-A missense mutation leading to the substitution of tyrosine for cysteine at amino acid position 282 of the protein product (C282Y). C282Y homozygotes account for 80%-85% of typical patients with HH.8 There are two other regularly identified mutations, one in which aspartate is substituted for histidine at amino acid position 63 (H63D), and the other in which cysteine is substituted for serine at amino acid position 65 (S65C). These are generally not associated with iron loading unless seen with C282Y as a compound heterozygote, C282Y/H63D or C282Y/ S65. Over the last 10 years, mutations of other genes coding for iron regulatory proteins have been implicated in inherited iron overload syndromes (e.g., hepcidin, hemojuvelin, transferrin receptor 2, and ferroportin). These are thought to account for most of the non-HFE forms of HH.