Screenings for people with hereditary hemochromatosis

The main guidance

The European Association for the Study of the Liver (EASL) published clinical practice guidelines on haemochromatosis in 2022, replacing its 2010 guidance. Its abstract says the stage of liver fibrosis and other organ damage should be assessed carefully at diagnosis, and that people with advanced fibrosis should be in a liver cancer screening program. (EASL guideline, 2022) An open-access 2023 review summarizes the EASL guideline in more detail and notes that of its 43 recommendations, 15 were based on expert opinion. (Review of EASL 2022, 2023) The American College of Gastroenterology (ACG) published a hereditary hemochromatosis guideline in 2019. (ACG guideline, 2019) The US Preventive Services Task Force (USPSTF) lists hemochromatosis screening as an inactive topic. (USPSTF, inactive topic)

Tests and checks the guidance lists

Check	Looks for	When	Source
Ferritin and transferrin saturation	Iron overload	First tests when hemochromatosis is suspected; in relatives	(Review of EASL 2022, 2023)(NHS, diagnosis)
HFE genetic test (C282Y)	The gene change behind most cases	When both iron tests are raised, or transferrin saturation stays raised; adult first-degree relatives	(Review of EASL 2022, 2023)(NHS, diagnosis)
Liver tests, liver stiffness (elastography) or FIB-4, liver MRI	Liver fibrosis and iron in the liver	At diagnosis	(Review of EASL 2022, 2023)(EASL guideline, 2022)(NHS, diagnosis)
Liver ultrasound and alpha-fetoprotein	Liver cancer	Every 6 months with cirrhosis or advanced fibrosis	(Review of EASL 2022, 2023)(EASL guideline, 2022)
ECG and echocardiogram	Heart involvement	With severe iron overload	(Review of EASL 2022, 2023)(NHS, diagnosis)
Blood sugar, joint, hormone and bone density (DEXA) checks	Diabetes, arthritis, hormone problems, osteoporosis	At diagnosis	(Review of EASL 2022, 2023)(NHS, diagnosis)(MedlinePlus)

Who is tested

The NHS says haemochromatosis can usually be diagnosed with blood tests: a full blood count, a liver test, a transferrin saturation test that shows how much iron in the blood is bound to transferrin, and a serum ferritin test that shows how much iron is stored. If these suggest haemochromatosis, a DNA test looks for the gene linked to the condition. It says to speak to a GP about testing if you have persistent symptoms, or if a parent or sibling has been diagnosed, even without symptoms. (NHS, diagnosis)

The EASL review says the first tests should be serum ferritin and transferrin saturation. People with raised ferritin (over 200 micrograms per liter in women, over 300 in men) together with raised transferrin saturation (over 45 percent in women, over 50 percent in men), and people with unexplained, persistently raised transferrin saturation, should have genetic testing. It says HFE C282Y homozygosity is found in more than 80 percent of people with clinically overt haemochromatosis, and that all adult first-degree relatives of people with haemochromatosis, particularly those homozygous for C282Y, should be offered genetic testing. (Review of EASL 2022, 2023) The ACG guideline notes that ferritin can also be raised in fatty liver disease and alcohol-related liver disease, which are more common than hemochromatosis in people with high ferritin who do not have the main HFE gene patterns. (ACG guideline, 2019) See iron test results and ferritin.

Liver checks

The EASL review says all people should be checked for liver fibrosis at diagnosis with non-invasive tests. It says a liver stiffness result of 6.4 kPa or less on transient elastography can rule out advanced fibrosis, and that FIB-4 was felt to be the most suitable blood-based score, though the evidence for it is limited. It says liver biopsy is now only recommended where cirrhosis is unclear and in people with ferritin over 1,000 micrograms per liter or abnormal liver enzymes. (Review of EASL 2022, 2023) The ACG guideline says a ferritin under 1,000 ng/mL at diagnosis identifies people at low risk of advanced fibrosis, and that MRI has made measuring liver iron easier and removed the need for liver biopsy in most people. (ACG guideline, 2019) See liver function test results and fatty liver screening and FIB-4.

Liver cancer surveillance

The EASL review says screening every 6 months with a liver ultrasound and an alpha-fetoprotein blood test is recommended for everyone with cirrhosis who could have cancer treatment. The 2022 guideline extends this to people with advanced (bridging, F3) fibrosis, including those whose fibrosis has improved with treatment, though it notes almost all people with haemochromatosis who develop liver cancer have cirrhosis and the F3 recommendation is weak. Risk factors it lists include being male, older age at diagnosis, diabetes and high, long-lasting iron overload. (Review of EASL 2022, 2023) See liver cancer surveillance.

Heart, joints, hormones and bones

The EASL review says effects outside the liver (skeletal, endocrine and sexual) should be checked in everyone, and that with severe iron overload the heart should be screened with an ECG and an echocardiogram, with a heart MRI if heart involvement is suspected. (Review of EASL 2022, 2023) The NHS lists further tests after diagnosis: a liver scan (Fibroscan) or MRI, an ECG or echo for the heart, rheumatology checks for joint disease, endocrinology checks for diabetes or Addison's disease, and a DEXA scan for osteoporosis. (NHS, diagnosis) MedlinePlus lists blood sugar, alpha-fetoprotein, echocardiogram, ECG, imaging and liver function tests among the tests that may be done. (MedlinePlus) See an ECG at a checkup and how often to have a bone density test.

When to contact a provider

MedlinePlus, hemochromatosis, when to contact a medical professional: (MedlinePlus)

Contact your provider if symptoms of hemochromatosis develop.

Contact your provider for an appointment (for screening) if a family member has been diagnosed with hemochromatosis.

Routine age-based screening

These checks are added to, not instead of, the routine screenings for your age and sex; see screenings by age and gender. For collecting the family history that makes relatives eligible for testing, see family history: when screening starts earlier.

Where they differ:

Population screening. The USPSTF has inactivated its hemochromatosis screening topic and does not keep an up-to-date recommendation; the EASL guideline and the NHS focus on testing people with raised iron tests, symptoms or an affected parent or sibling. (USPSTF, inactive topic)(Review of EASL 2022, 2023)(NHS, diagnosis)
Who gets liver cancer surveillance. The 2022 EASL guideline includes people with advanced (F3) fibrosis as well as cirrhosis, as a weak recommendation; its 2010 guidance recommended it for people with cirrhosis. (Review of EASL 2022, 2023)
How liver fibrosis is judged. The ACG guideline uses a ferritin under 1,000 ng/mL at diagnosis to identify low risk of advanced fibrosis; the 2022 EASL guideline gives more weight to liver stiffness measurement, with 6.4 kPa or less ruling out advanced fibrosis. (ACG guideline, 2019)(Review of EASL 2022, 2023)
Transferrin saturation in follow-up. The EASL review says it is not recommended for monitoring iron levels during treatment, because it can stay raised after ferritin is in range. (Review of EASL 2022, 2023)

Your doctor decides what your result means for you.

Questions people ask

Who should be tested for hemochromatosis?

The 2022 EASL guideline, as summarized in an open-access review, says people with raised ferritin (over 200 micrograms per liter in women, over 300 in men) and raised transferrin saturation (over 45 percent in women, over 50 percent in men), and people with unexplained, persistently raised transferrin saturation, should have genetic testing. The NHS says to talk to a GP about testing if a parent or sibling has been diagnosed, even without symptoms. (Review of EASL 2022, 2023) (NHS, diagnosis)

Should relatives be tested?

Yes. The EASL review says all adult first-degree relatives of people with haemochromatosis, particularly those homozygous for C282Y, should be offered genetic testing. MedlinePlus says screening family members of a person diagnosed may find the disease early, before organ damage. (Review of EASL 2022, 2023) (MedlinePlus)

Is there population screening for hemochromatosis?

Not from the USPSTF. It lists hemochromatosis screening as an inactive topic: it has decided not to review the evidence and update its recommendation, and says the earlier review may be out of date. (USPSTF, inactive topic)

Why is the liver checked at diagnosis?

The EASL guideline says the stage of liver fibrosis and other organ damage should be assessed at diagnosis because they guide care. The ACG guideline says a ferritin under 1,000 ng/mL at diagnosis identifies people at low risk of advanced liver fibrosis and should be used routinely in the first evaluation. (EASL guideline, 2022) (ACG guideline, 2019)

Who needs liver cancer surveillance?

People with cirrhosis, and in the 2022 EASL guideline also people with advanced (bridging, F3) fibrosis. The review says ultrasound and alpha-fetoprotein every 6 months is recommended for people with cirrhosis who could have cancer treatment, and notes the F3 recommendation is weak. (EASL guideline, 2022) (Review of EASL 2022, 2023)