British guidelines for diagnostic and treatment pathways were updated in May 2018 following the publication of an important paper and recommendations by professors Edward J. Fitzsimons, Jonathan O. Cullis, Derrick W. Thomas, Emmanouil Tsochatzis and William J. H. Griffiths in April 2018.
The guidelines are published in full at this link >> https://b-s-h.org.uk/guidelines/guidelines/diagnosis-and-therapy-of-genetic-haemochromatosis-review-and-2017-update/
Haemochromatosis UK is very pleased to see these guidelines in place after many years of uncertainty and inconsistency. The charity wholly endorses and advocates the guidelines and strongly encourages patients to ensure that their consultants and venesection teams work to them. The European Association for the Study of the Liver guidelines are also relevant, and of course these recommendations should be considered in the context of each patients own individual clinical situation
The BSH guidelines contain 11 basic recommendations, which are summarised below. The rationale for these recommendations is set out in detail in the published scientific paper.
Looking at each of the 11 recommendations in turn:
Recommendation 1: Unselected population screening for HFE gene mutation is not recommended.
Haemochromatosis UK accepts the rationale for this, given that penetration is known to be low. However we maintain strongly that there needs to be a vastly improved readiness amongst primary healthcare professionals to test on the presentation of common symptoms in combination.
Recommendation 2: Genetic haemochromatosis (GH) patients who present with serum ferritin (SF) >1000 microgrammes per litre (µ/l) and any with raised transaminases should be referred to a hepatologist for fibrosis assessment and exclusion of cirrhosis.
This has long been Haemochromatosis UK’s understanding of good practice and we are delighted to see it formalised in this way. In these circumstances we would expect to see liver iron concentration and liver condition assessed using MRI scanning technology (Fibroscan or LiverMultiScan).
Recommendation 3: Liver biopsy is no longer required for diagnosis of HFE GH but may be required to assess the severity of fibrosis in GH patients with SF >1000 µ/l and/or elevated transaminases. Transient elastography could be used to select which patients from this group require liver biopsy.
Haemochromatosis UK agrees that biopsy, which is invasive, painful and expensive, should be used only where necessary.
Recommendation 4: Patients of north European ancestry with clinical features suggestive of GH should have the following laboratory investigations; full blood count (FBC), liver function tests (LFTs), serum ferritin (SF) and transferrin saturation (Tsat). Molecular testing for HFE GH should follow if results fulfil the criteria of recommendation 5.
Recommendation 5: All adult patients of north European ancestry with unexplained raised SF and random Tsat (>300 µ/l and >50% males; >200 µ/l and >40% females) and normal FBC should have molecular (genetic) testing for HFE GH.
As the cost of such testing falls and access improves there is no longer any reason not to seek an early molecular diagnosis in order to inform families and, if necessary, confirm a diagnosis. However waiting for the results of such testing should not be allowed to delay the start of venesection therapy if SF and TSat levels are high.
Recommendation 6: Laboratory screening to include FBC, LFTs, SF, Tsat and HFE (genetic testing) should be offered to family members after the diagnosis of HFE GH. Family screening should include parents, siblings, partner and children (over the age of consent). Extended family screening is not recommended if an individual is identified as a C282Y/H63D compound heterozygote.
Haemochromatosis UK is very pleased to see strong, clear recommendations for family screening. We also advocate that this is applied to families of compound heterozygotes.
Recommendation 7: Investigation of all confirmed C282Y homozygotes should include FBC, LFTs, SF and Tsat. Thereafter further investigation may be required as follows:
a. SF <1000 lg/l, normal LFTs, normal clinical examination; no further investigation required. Follow recommendation 8.
b. SF >1000 lg/l and or abnormal LFTs. All such patients require referral to Hepatology for fibrosis assessment to exclude the presence of cirrhosis. A minimum would be elastography. For patients with confirmed cirrhosis monitor with a-fetoprotein (AFP) and hepatic ultrasound every 6 months (recommendation 11).
Haemochromatosis UK would also like to see further investigation as a result of raised transferrin saturation.
Recommendation 8: Non C282Y homozygotes with significant iron loading as confirmed by magnetic resonance imaging and or liver biopsy should be investigated for rare iron loading genotypes or digenic inheritance.
Haemochromatosis UK is pleased to see this included as it is evident that the genetics of haemochromatosis is much more complex than has been believed in the past.
Recommendation 9: At diagnosis, all fit GH patients with biochemical iron loading should undergo weekly venesection until SF is 20–30 µ/l and Tsat <50%. During this phase of venesection FBC should be monitored weekly and SF / Tsat monitored monthly. Homozygotes with normal iron indices and compound heterozygotes with minimal elevation of iron indices may be suitable for blood donation and annual monitoring of SF and Tsat.
Recommendation 10: During maintenance, venesect as required, preferably at a blood donation centre to maintain normal FBC, SF <50 lg/l and Tsat <50%.
We are delighted to see these aspect of treatment so clearly defined for both the de-ironing phase and maintenance phase; this ensures consistency across the UK.
Recommendation 11: HFE GH with cirrhosis; Treat as per recommendations 9 and 10 but not suitable for blood donation. Monitor AFP and hepatic ultrasonography every 6 months.
It is notable that the lower we can drive the average age of diagnosis, the less likelihood there is that a patient will load iron to the extent that the liver is damaged by cirrhosis and then liver cancer.