Incidence	- prevalence of homozygotes in the caucasian population is 1 in 400 - prevalence of heterozygotes in the caucasian population is 1 in 10
Age	- most cases present in the fifth decade
Sex	- clinical manifestations occur more commonly in men - probably due to greater physiological iron loss and reduced intake in women
Geography
Aetiology	- autosomal recessive inheritance - mutation in HFE gene on chromosome 6 - there is a history of alcohol excess in 25% of cases; increases likelihood of iron overload, but does not cause HH - mechanism of damage - HFE gene may be involved in regulating expression of the divalent-cation transporter; iron is taken up by mucosal cells inappropriately, exceeding transferring binding capacity - excess iron is taken up in the liver; it is thought that the iron itself causes the damage
Presentation	- classical triad - bronze skin pigmentation, hepatomegaly and diabetes mellitus (only present in gross iron overload) - hypogonadism 2º to pituitary dysfunction; however, rarely symptomatic - chondrocalcinosis -> arthropathy
Investigations	Homozygotes - serum iron is raised > 30 µmol/L - TIBC is reduced - comlete or almost complete transferrin saturation - serum ferritin is elevated > 500 µg/L - LFTs - often normal even in established cirrhosis Heterozygote - may have normal biochemicall tests or a mild increase in serum transferrin saturation or ferritin Liver biopsy - >180 µmol/g iron indicates HH MRI - dramatic reduction of signal intensity of liver and pancreas - in secondary iron overload (haemosiderosis), the pancreas is spared
Macro	- total body iron content is 20-40 g, c.f. 3-4 g in a normal person - iron content in liver and pancreas is 50-100 times normal - also increased level in endocrine glands, heart and skin - gonadal function is impaired - liver shows extensive iron deposition and fibrosis
Micro	- iron is initially deposited in periportal hepatocytes - later distributed widely throughout acinar zones, biliary duct epithelium, Kupffer cells and connective tissue
Staging
Serum markers
Management	Venesection - prolongs life and may reduce tissue damage; however, if cirrhosis is present, does not reduce risk of HCC - venesection of 500 mL twice weekly for up to two years - monitor serum iron, ferritin and MCV - these fall only once the iron is depleted - 3-4 venesections per year are required subsequently to prevent iron accumulation - manifestations improve apart from testicular atrophy, diabetes and chondrocalcinosis Chelation therapy - in patients who cannot tolerate venesection due to severe cardiac disease or anaemia, chelation therapy with desferrioxamine may be successful Screening - screen all first-degree family members to detect early, asymptomatic disease - serum ferritin - genetic markers - serum iron and transferrin saturation are the best and cheapest tests available
Prognosis	- course depends on sex, dietary iron intake, presence of associated hepatotoxins (e.g. alcohol), genotype
Complications	- 30% of HH patients with cirrhosis will develop 1º HCC; this is rare if the disease is diagnosed early and the excess iron is removed

Hepatobiliary medicine

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