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Hereditary hemochromatosis

What's new

Updated 2023 APASL guidelines for the diagnosis and management of hereditary hemochromatosis.

Guidelines

Key sources

The following summarized guidelines for the evaluation and management of hereditary hemochromatosis are prepared by our editorial team based on guidelines from the Asian Pacific Association for the Study of the Liver (APASL 2023), the European Society of Cardiology (ESC 2023), the European Association for the Study of the Liver (EASL 2022,2010), the American College of Gastroenterology (ACG 2019), the ...
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Screening and diagnosis

Indications for screening, general population: as per APASL 2023 guidelines, do not obtain screening for HH in the general population.
D
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  • Indications for screening (family relatives)

  • Indications for testing

Diagnostic investigations

Clinical assessment: as per EASL 2010 guidelines, assess patients with HFE hemochromatosis for end-organ complications, including diabetes mellitus, joint disease, endocrine deficiencies, cardiac disease, porphyria cutanea tarda, and osteoporosis, before initiating treatment with phlebotomy.
B

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  • Iron panel

  • MRI

  • Assessment of liver fibrosis

  • Evaluation for extrahepatic manifestations

  • Genetic testing

Diagnostic procedures

Liver biopsy
As per APASL 2023 guidelines:
Consider performing a liver biopsy after initial laboratory testing to assess the level of hepatic iron loading and liver fibrosis.
B
Consider performing a liver biopsy to assess for advanced hepatic fibrosis in patients with verified HFE-hemochromatosis with any of the following noninvasive markers:
serum ferritin > 1,000 mcg/L
B
hepatic iron concentration > 200 mcmol/g by magnetic resonance methods
B
APRI > 0.44
FIB-4 index > 1.1
mobilizable iron stores > 9.6 g
B
transient elastography liver stiffness measurement > 13.9 kPa
B

Medical management

General principles: as per APASL 2023 guidelines, evaluate the phenotype of p.Cys282Tyr/p.His63Asp compound heterozygous patients and identify factors that may alter serum iron indices and/or increase hepatic iron stores or cofactors for liver disease expressivity.
A

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  • Treatment targets

  • Iron chelation therapy

  • Hepcidin agonists

  • PPIs

  • Management of complications

Nonpharmacologic interventions

Dietary modifications: as per APASL 2023 guidelines, advise adopting a healthy lifestyle, including maintaining normal body weight and limiting alcohol consumption, in patients with hemochromatosis. Do not restrict dietary iron intake but advise avoiding iron supplements.
B

Therapeutic procedures

Therapeutic phlebotomy
As per APASL 2023 guidelines:
Perform phlebotomy in patients with p.Cys282Tyr/p.His63Asp compound heterozygosity or p.His63Asp homozygosity with significant iron loading. Consider performing phlebotomy in patients with mild iron overload if symptomatic.
A
Initiate a venesection program in patients with elevated serum ferritin concentration.
A

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  • Erythrocytapheresis

Surgical interventions

Liver transplantation: as per APASL 2023 guidelines, offer liver transplantation in patients with decompensated liver disease and/or HCC. Recognize that the risk of recurrence of hepatic iron loading is very low after liver transplantation and take into consideration the alternative causes should it occur.
A

Specific circumstances

Young patients
As per APASL 2023 guidelines:
Obtain genetic testing for HFE- and non-HFE-hemochromatosis in < 30 years old patients presenting with iron overload. Obtain an accurate assessment of the degree of iron overload affecting the liver and heart.
B
Perform early phlebotomy for the best prognosis.
B

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  • Pregnant patients

Preventative measures

Hepatitis A and B vaccination: as per EASL 2010 guidelines, consider providing hepatitis A and B immunization in patients with HFE hemochromatosis despite ongoing evidence of iron overload, to minimize the risk of additional complications.
C

Follow-up and surveillance

Indications for specialist referral: as per EASL 2022 guidelines, refer patients with evidence of significant, unexplained iron overload for assessment by a specialist in iron disorders.
B

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  • Ferritin monitoring

  • Cardiac imaging follow-up

  • Surveillance for HCC