Episode Transcript
[00:00:00] Speaker A: Welcome to ingest, the podcast series designed for primary care clinicians and brought to you by the Primary Care Society for Gastroenterology. My name is Charlie Andrews, a GP with an extended role in gastroenterology based in Midsummer Norton near Bath.
This is an educational podcast bringing you engaging and interesting conversations with experts within the field of gastroenterology, talking about how to diagnose, when to refer, and how to support the management of patients with common gastrointestinal conditions.
In this episode, I'm talking to Dr. Jeremy Shearman. Jeremy is a consultant gastroenterologist based in Warwick and he has a particular interest in liver disease and is an expert in hereditary haemochromatosis.
During this episode, we're going to be talking about iron overload and hereditary haemochromatosis. We're going to be exploring how iron is regulated and and manage within the body. We're going to be looking at causes of raised iron levels and then we're going to be focusing our talk on hereditary haemochromatosis. So, Jeremy, welcome to the podcast. We're going to be talking about hereditary haemochromatosis, but to really understand that, I think it'd be helpful if we went back to the basics and talked a bit about iron. So can we talk about iron metabolism regulation? Where do we get it from? Can you tell us a bit more about that?
[00:01:27] Speaker B: Thanks, Charlie. So most of our colleagues will appreciate that iron metabolism is very important for life on this planet. It's the crucial atom that transports oxygen around mammalian systems.
So it's pretty fundamental. In humans, as in other mammals, the regulation of iron stores is very tightly regulated in that iron deficiency is obviously associated with morbidity and harm. But equally, iron overload can be very toxic and very damaging.
That control mechanism is largely based at the point of iron absorption.
So humans, like any other mammals, are unable to excrete iron, and therefore there is a fairly well evolved system that will sense body iron stores and will limit dietary iron absorption when iron stores are replete.
So the amount of iron we absorb from our diet is actually quite small to the total amount that's in transit around the body. But it's that crucial regulation of iron absorption that is really critical to iron balance.
[00:02:38] Speaker A: Thank you, Jeremy. I've heard of something called hepcidin. Does hepcidin play a role in regulating absorption of iron?
[00:02:46] Speaker B: Yes. So hepcidin is an interesting hormone.
Hepcidin was first identified as a molecule that was involved in the innate immune response, but it's now recognized as being the main humoral transporter or messenger hormone of iron regulation.
And it's been demonstrated now that an abnormal HFE protein, as in hemochromatosis, reduces circulating hepcidin, which then prevents there being a break on further iron absorption from the gut.
[00:03:22] Speaker A: So we've looked there at the regulation of iron stores and you've touched on why it's very important that we keep these in balance.
What would you consider to be a high iron level?
[00:03:35] Speaker B: So that's been a topic that we've discussed quite a lot over recent times through the hemochromatosis special interest group, because most of our colleagues will be familiar with the laboratory measures of iron metabolism.
So, for instance, colleagues in primary care will be very familiar with the use of ferritin. Ferritin, as a molecule, is an ion storage protein.
It sequesters a large number of iron atoms in the intracellular compartment and effectively prevents the cell from the toxicity of iron overload.
In laboratory science, we measure soluble ferritin, which is a fragment of ferritin, which is present within the blood. And historically, we've assumed that ferritin levels are associated with iron stores.
Now, when evaluating iron deficiency, a low ferritin is a reliable measure of iron deficiency, but when you get to high ferritin levels, it becomes less reliable.
And many of our colleagues may remember from medical school learning that ferritin is an acute phase reactant and therefore its transcription becomes upregulated during inflammation. And we've also witnessed that a lot of other conditions that are very common in primary care, such as alcohol use disorder and fatty liver disease, also seemingly lead to an increase in ferritin transcription in certain individuals.
The parallel test is transferring saturation, and I think that's a test that actually is less familiar to GP colleagues. Transfer in saturation is effectively reflection of the amount of iron that's transported around the body. It historically used to be calculated by dividing the total serum ion by the tibc, or the total ion binding capacity. But most laboratories will now measure or report transfer and saturation per se, provided you request it.
And I think one of the things that we've realized is that ferretin requests from primary care are very high. But we're trying to encourage laboratories to think about reflex testing of transferring saturation when the ferritin is high.
But going back to the figures, there are reference ranges for laboratories which vary from laboratory to laboratory, depending on which platform they're using for ferritin.
But the current guidelines from the European association that study the liver set a ferritin threshold of somewhere between 250 and 300, and anything above that is considered high.
Transfer and saturation as a test is probably a little bit more reliable. And broadly speaking, transfer and saturation should usually be 50% or less. It is very labile and will go up after meals and with other factors. So each of the tests is unreliable. But the key message is, if you've got a high ferritin, always first think about checking the transfer in saturation.
[00:06:30] Speaker A: Thank you. That was a really clear overview of the various tests that we have available, and I fully agree. I think that reflex testing and reducing the friction for primary care colleagues would be really useful in this sort of area and to try and help speed up diagnosis.
We're going to talk a bit about high iron levels and the causes of that. We're very familiar in primary care with investigating iron deficiency, but actually perhaps less confident in investigating and understanding the causes of raised iron levels. Could you talk a bit about some of those causes for us now?
[00:07:04] Speaker B: Yeah, I think that's a really key question and I think what it really boils down to is if you check a ferritin in a patient and it comes back unexpectedly high, I think the first question any clinician's got to try and answer is whether they think that reflects iron overload.
That's the first thing, because the identification of iron overload and its early treatment is really key. So the first step towards that would be to do the transferring saturation. If that's very high, then think about requesting genetic analysis for hfe, which you might come onto later on.
The studies that have been reported in the UK previously have demonstrated that if you take a population of patients with a high ferritin, probably iron overload only accounts for about 10% of that.
And I would say in 21st century clinical practice, the dominant conditions which will cause a high ferritin in the absence of iron overload are really fatty liver, or mazzled, as we now call it, and alcohol use disorder.
I still think there's probably work that we need to do to understand what. What it is about the high ferritin in those patients.
So it's not that every patient with fatty liver will necessarily have a high ferritin or every patient who drinks to excess will have a high ferritin, but those are the two things that I think would dominate most of primary care practice currently.
[00:08:31] Speaker A: So from that I can infer that 10% of patients will have this iron overload picture. So raised iron, raised ferritin level and a high transfer and saturation, whereas about 90% are going to be related to the causes that you've just mentioned there, Jeremy. So, MASLD and alcoholic liver disease. And also I'm aware that in inflammation we can see high iron levels as well, so we might therefore see high ferritin and a normal or low transfer in saturation. That seems to be my understanding of those tests.
So now let's move on to hereditary haemochromatosis. So could you give us a bit of background about what that condition actually is?
[00:09:14] Speaker B: Sure. So, hemochromatosis. I think most colleagues will think of hemochromatosis as a fairly sort of quaint niche subject that comes up in exams and never appears in real life. But hemochromatosis we now know to be the commonest single gene genetic disorder to affect Northern Europeans.
And the journey to that statement goes back over a century.
When it was first described, hemochromatosis was really the overt manifestation of very high iron overload. And so it had this title of bronze diabetes. Because there was heavy iron loading in the liver, in the heart, the pancreas. The patient had pigmentation due to stimulation of melanocytes stimulating hormone, and it was pretty rapidly fatal. For many decades it was thought that this might just be a variant of alcoholic liver disease.
And the first suggestion that this was a genetic condition really came in the 1970s when a very astute transfusion doctor in France noticed an association between hemochromatosis and HLAA3.
And that then led to the recognition that there was a genetic condition. But it also meant that the gene responsible was on the short arm of chromosome 6.
There was then a 20, 25 year hunt really to identify that gene that culminated with the identification of HFE in 1996.
And pretty soon after that discovery, we recognized in the UK that 90% of patients with haemochromatosis are homozygous for the common C282Y mutation.
Subsequent analysis from UK Biobank has demonstrated the high prevalence of C282Y homozygosity in the UK in particular.
And so in essence, we now know by extrapolation from the Biobank data that the UK will have somewhere between 380,000 and 400,000 individuals genetically predisposed to iron accumulation.
And that puts us second only to the Republic of Ireland in terms of burden of patients with haemochromatosis.
The reason why colleagues will find that somewhat staggering is relates to the relatively delayed penetrance of the condition.
The Genetic mutation doesn't make patients look or feel unwell, but what it does is it dysregulates that iron absorption pathway. So people gradually accumulate iron. And a subsequent study from colleagues in Exeter has shown that by age 80, 56% of males who are C282Y homozygous will express iron overload. But by that point they will also have significant morbidity. The figure in women is a little bit lower, it's about 40%, and that's due to the fact that during their reproductive years, there is additional use of iron, so they effectively have a delayed phenotypic expression. But it is a common condition and it's under the surface in many of the patients that you'll see in primary care. And one of the concerns I have, and that I'm trying to sort of develop, is that iron is a hidden CO factor for the current burden that we experience in liver disease in the uk.
[00:12:36] Speaker A: So, based on what you've been saying, it sounds like a lot of patients won't have any overt symptoms or signs of haemochromatosis.
So how would you, Would you advise that we identify patients who are either at risk or who may have haemochromatosis in our everyday frontline roles?
[00:12:54] Speaker B: Yeah, I think that represents the perennial challenge of trying to diagnose conditions before the pathology is too overt. And I think that's one of the challenges we have in 21st century medicine, is we're looking to identify opportunities to make early diagnoses.
Historically, haemochromatosis has been associated with various symptoms, but most of those symptoms are relatively non specific.
So old textbooks would describe abdominal pain and fatigue. Actually, more recent studies of patients and their symptom burden actually identifies joint pains actually as a very dominant part of the presentation. The concern of patients, actually, in clinical practice, you know, my practice, I would say that probably a third, maybe a half, of my patients have been found fortuitously. So they may describe a degree of fatigue, they may have a ferritin checked by a gp, expecting that the patient's going to be iron deficient and paradoxically, the ferritin level comes back high and associated with that. We also have an increasing number of patients who've been identified by cascade screening, where the first degree family members of a patient with haemochromatosis are recommended to get tested and then they're fortuitously identified at an early stage.
So in terms of symptoms, fatigue, and I guess that represents a huge slice of patients in primary care. If I suggest joint pain and arthralgia as another. Again, that's probably not very rare in primary care, but it's worth bearing in mind that the joint discomforts, the joints that are particularly associated with hemochromatosis tend to be a little bit unusual, so they tend to be second and third metacarpophalangeal joints and ankles.
So if you've got someone with hand arthritis, particularly second and third metacarpophalangeal joints or ankle problems, and it's always worth thinking about haemochromatosis as a potential explainer for that patient.
[00:15:03] Speaker A: And how commonly are liver related problems, I.e. abnormal liver enzymes a presenting feature of hereditary haemochromatosis?
[00:15:12] Speaker B: I don't think we've done a recent survey that would actually reveal that information just yet. I mean, there may be opportunities to look into that in the not too distant future.
Clearly, as a hepatologist myself, it was always drummed into me at an early stage that if you see someone in clinic who's got a raised alt, you take a good history from them, you understand about their alcohol use, you need to understand their family history, you need to think about their morphology and whether they might have fatty liver disease. But one of the fundamental components of a liver screen, as we used to call it, would be to measure the ferritin, the transfer and saturation, along with autoimmune markers. Because if you don't test for it in those patients with an isolated raised alt, then you might never make the diagnosis.
[00:15:58] Speaker A: Can we talk a bit about next steps now? So if we've tested the ferritin level and it's come back high, and that could be because of symptoms, it could be as part of a fatigue screen, for example. What would our next step be? What test should we be considering at this point?
[00:16:16] Speaker B: If the ferritin is elevated and you think the symptoms would be consistent with a diagnosing chromatosis, it's always useful to have done the transfer and saturation.
If you've got a high ferritin and a high transfer in saturation, the next step would be to request HFE mutation analysis. Now, I know from conversations with GP colleagues across the country that a there's sometimes drags people slightly outside their comfort zone and furthermore, I think there is quite variation in terms of the barriers that they perceive with accessing tests of that nature with their local laboratory.
So I wouldn't be too prescriptive and say, you must do this, but I think the logical next step, from the patient's point of view is to have their genotype clarified. And the genotype that's associated with a high risk of iron loading and the morbidity associated with haemochromatosis is unequivocally the C282Y homozygosity. So that's the C282Y mutation on both chromosomes.
We can talk later, if you wish, about some of the other genotypes, which often cause confusion. But in terms of making a positive diagnosis of hemochromatosis, it's C282Y homozygosity that you really need to be looking for.
[00:17:37] Speaker A: Could we look at some of these other genotypes now, Jeremy? Just have a discussion around those?
[00:17:42] Speaker B: Yes.
And it's quite a difficult subject. And it's quite a difficult subject. So, in the original report of the HFE Gene Back in 1996, the paper published two mutations. The dominant one was C2H2Y.
And because of the input of the geneticists in that study and the fact they were looking at a population of American patients with hemochromatosis, the prevalence of the C282Y in their patients wasn't sufficient to explain all the cases.
So they looked for other mutations and they identified the second mutation, called 863D.
Now, in terms of the impact on the secondary and tertiary structure of the protein, 863D is not thought to be very disruptive.
And to cut a long story short, H63D has been tested by laboratories for many years, but we now have pretty compelling evidence from UK Biobank that the genotypes associated with H63D do not infer the risks of hemochromatosis, I.e. the bad outcomes, the cancer risks, the joint disease risks, the liver disease risks and things of that nature.
So to this day, laboratories, when you request HFE mutation analysis, will report both C282I and 863D.
But for a primary care audience, I would strongly recommend that everyone focus primarily and personally almost exclusively on C282Y.
[00:19:19] Speaker A: That's really helpful and useful to know and will help me to understand the reports I get back from the genetic labs. Now, can we now look at cascade testing and maybe talk through a scenario that is quite common in primary care. Something I see, not infrequently, whereby a patient may say to me that a family member has been diagnosed with haemochromatosis and they'd like to be tested, or the patient comes in with a letter saying that a family member has been diagnosed how would we approach that situation?
[00:19:51] Speaker B: Yeah, so this is a really important topic and I think it's worth stressing for the listeners that the concept of cascade screening in haemochromatosis predates the identification of the HFE gene. So back when I was a trainee physician, whenever making a diagnosis of hemochromatosis, you would test first degree family members. And what we would do in those days is we would measure their ferritin and transfer in saturation.
If they were normal, you might recommend that those tests be repeated at two or five yearly intervals. The identification of the HFE mutations and particularly the association of C282Y homozygosity has made cascade screening much more accurate.
So nowadays, if I see a patient who has haemochromatosis and is a C2 8 2R homozygote, I'll give my patient a letter for each of his first degree relatives and I'd advise the patient to give those to the relatives. And once they've given it to their relative, they've exercised their responsibility regarding cascade screening. The yield in terms of new cases obviously much higher in siblings, but a lot of patients are more concerned or as concerned about their children.
And interestingly, we are living in an era where patients may be diagnosed relatively young. And therefore offering screening to parents is not always necessarily inappropriate either. Obviously you've got to take the parents age and their state of health into consideration when doing that. But the screening can be done with a combination of ferritin transfer, saturation and HFE mutation analysis.
[00:21:37] Speaker A: Something that I've noticed is that there can sometimes be pushback from labs in terms of testing for HFE gene analysis in someone who hasn't got overt iron overload, that is a family member of someone who is homozygous. Should we be doing all of the tests together? So, for example, a ferritin transfer and saturation and a HFA gene analysis, or should we doing just two of them? What's your advice around that?
[00:22:05] Speaker B: Yes, I would do. And I think the key, I think sometimes to unlocking that is that if you put on the request form family history of haemochromatosis, I think it'd be very difficult for any laboratory to actually then refuse that referral.
Now that then generates this other interesting topic, which is if you identify someone who's a C2 8 2R homozygote, but no evidence of iron loading and nobody's quite known how to manage or even what term to use for that group of patients. I've been Quite keen on popularizing the use of the word latent hemochromatosis, because we know they're genetically at risk, but even if they're not iron loaded at the time, we know that they'll be at risk of iron loading later in life, and therefore to convey the risk to the individual so that they do get monitored is quite important.
[00:23:00] Speaker A: So we talked about how to detect and how to assess for haemochromatosis and iron overload. Can we now talk about referral? Now, this might sound very obvious because I'm speaking to you, Jeremy, a hepatologist, but who do we actually refer these patients to? Because some people might be thinking that this is a referral to haematology, whereas others might be thinking gastroenterology and haematology.
Can you clarify for us?
[00:23:25] Speaker B: Yeah. So it will vary from region to region.
And I think that the position I've always taken on this is it doesn't really matter if someone sees a hepatologist, a gastroenterologist or a haematologist, provided the person they see does have an interest and provided a certain amount of basic assessment of the patient goes on.
So in hepatology, we've naturally always been concerned about the development of liver disease and the risk that these patients have of developing hepatocellular cancer.
So, as a hepatologist, if we see someone who's iron loaded, we'll evaluate their iron load, get them treated, but we would also undertake an assessment of their liver fibrosis. So we do a fibrous scan or an ELF test, and patients who are harbouring significant liver fibrosis at the time of diagnosis should be offered HCC surveillance by way of six monthly ultrasounds.
Now, that's something that is perhaps, probably more in the consciousness of hepatologists than it is haematologists, but it's something that we're trying to work through the special interest group, to ensure that there is a standard approach to patients assessment. Because, as you are probably aware that we've had historically, we've become very siloed in terms of our secondary care mentality.
There's quite good templates for what these patients need. We just need to make sure that the patients get the right tests, but it will vary. And the special interest group, we've got hematologists, gastroenterologists and hepatologists involved in that. It's really a case of finding who in your locality has that interest. And sometimes you find that out through the day case unit, because in many instances, when people are going through the induction treatment, that is the intensive venous section. They'll be well known to the lead nurse in the daycase unit and they'll often tell you which of the consultants actually has the particular interest and will provide that clinical oversight of the patient's care.
[00:25:30] Speaker A: You've nicely brought us onto the topic of management there and treatment of haemochromatosis, Jeremy. So do you think you could expand on that and tell us about how we manage patients with hereditary haemochromatosis?
[00:25:42] Speaker B: Yeah. So hemochromatosis is still treated by venous action and it's quite an interesting treatment. It's one of the most fundamental therapies that humans have exercised on other humans since the dawn of time.
And there aren't many remaining indications for therapeutic venous section or bloodletting, but hemochromatosis in the UK is probably the commonest. And the principle behind venussection is that if a patient is heavily iron loaded, we remove blood from the patient on a weekly basis.
The removal of the erythrocytes stimulates erythropoiesis, which in turn uses up the existing iron stores.
And so we will venousect the patient intensively, monitoring the ferritin, usually on a monthly basis, and whatever their ferritin started at will go through that induction period. And until the ferritin is down to below 100, preferably between 50 and 100, the duration of that induction period will vary from patient to patient.
And it's been well demonstrated over recent decades that due to earlier diagnosis, the time that people need in induction treatment is less now than it used to be. But certainly when I was a junior, some patients would face the prospect of weekly venous section for 12 or 18 months to be deioned.
Once that excess iron has been removed by venous section, the patients then enter what we call maintenance phase treatment. And for most patients, that would constitute a venous section between two and six times a year, depending on the individual. And that's really intended just to keep them in iron balance and to prevent them from further reaccumulating iron.
[00:27:29] Speaker A: And how could we in primary care support these patients who are going through treatment for iron overload and hereditary haemochromatosis?
[00:27:39] Speaker B: One would be to support the process of cascade screening.
And I say that for a couple of reasons. One is because the patients themselves sometimes feel uncomfortable that their family members may be affected. So an open arms and a progressive approach to cascade screening is very useful, but also because by cascade screening, we are going to identify more patients who would benefit from assessment, monitoring and possibly treatment.
The patients who are being treated, like all patients, they do vary. Many patients, once they're established, they've been de ironed, they're on treatment. A lot of patients actually are quite able to look after themselves and actually, you know, can get on with their lives.
But sometimes there will be challenges, there'll be challenges in terms of access to Healthcare.
Since 2020, the NHSBT blood Transfusion Donor Service have been prepared to accept haemochromatosis donors, which makes life easier for some patients. But I think we shouldn't underestimate that patients having to visit hospitals in order to have treatment constitutes quite a burden on their time and sometimes cost.
So the more that we can displace treatments into patients own localities and fit in with times that suits the patient, the better. But I think that is really behoven on us in secondary care to provide outreach treatment services and signpost patients to the blood transfusion service where we can.
[00:29:15] Speaker A: I suspect, Jeremy, that these patients will need some monitoring of their bloods once they've been diagnosed. So I was just wondering, how frequently in primary care should we be checking the bloods of a patient with hereditary haemochromatosis?
[00:29:29] Speaker B: I think that's a good question, but I think, with respect, Charlie, I think at the moment, I think the responsibility for oversight and monitoring of treatment probably should sit in secondary care.
And I say should sit in secondary care because my sense is that there are some parts of the country where a lot of the treatment gets overseen and monitored largely by very capable and senior nursing staff in the day case units.
And one of the standards that I think we're trying to encourage is that every patient with haemochromatosis should have some clarity as to who their responsible clinician is, in that each time they attend for venous section, they will have blood tests monitored. So typically when patients attend for their venous section, they'll have a haemoglobin checked, but they'll also have a ferritin and a transfer and saturation checked. And that's how within secondary care we then monitor the frequency of maintenance venosection.
Alongside that, as said earlier, in patients who are cirrhotic, they probably or they should remain under six monthly ultrasound. And again, that really should be the responsibility of the local secondary care provider. So if you have patients who are uncertain as to who's providing oversight to their treatment, I think your responsibility in primary care is probably to dig a little bit deeper and, and find out who in the hospital should be providing the patient the oversight.
It's not complicated work, but I just think it naturally fits currently within secondary care.
[00:30:58] Speaker A: This is clearly a lifelong condition and it will have a significant impact on patients once they're diagnosed, even just to the point of having to go to the hospital on a regular basis.
So do you have any resources, Jeremy, that you often signpost patients to, to allow them to have some support and advice following their diagnosis?
[00:31:19] Speaker B: So we're working quite closely at the moment with the British Liver Trust and the British Liver Trust, as you might know, is a large, well resourced charity that provides great patient information for all liver conditions.
We've found a patient group who are working with the British Liver Trust and we're looking to update some of the data on the British Liver Trust website to facilitate that. I sit on the scientific committee of epaf, which is the European Federation of Association of Patients with Haemochromatosis, which links together all the European patient associations and also has close links with Haemochromatosis International and Haemochromatosis Australia.
So there is a lot of information out there. One of the things we're trying to do through the EPAF Scientific committee is actually harmonize some of that advice. And in fact, we're just finalizing the wording of a document that we're hoping will be hosted by the British Liver Trust that will help address some of the common questions that patients ask about the condition.
[00:32:27] Speaker A: We're coming to the end of the episode now, Jeremy, and before I ask you for your key take home messages, I'd just like to ask you a question that I have asked on a few episodes recently and I think is quite a helpful question and gives you the opportunity to really show us your enthusiasm for the topic and why we should be here. But the question is, why should our gps be listening to this episode about hereditary haemochromatosis and iron overload?
[00:32:53] Speaker B: The key answer to that question, Charlie, is it's a very common condition and yet as a common condition, it's commonly missed and commonly misdiagnosed.
So I think Paul Adams, in his Lancet article from last year, I think came up with the phrase that it is, you know, we're concerned with missed diagnosis, that is patients who are at risk who haven't been identified. But we're also interested in misdiagnosis, I.e. people who've been inappropriately attached the label on the basis of a high ferritin.
So this is the sort of stuff that is quite common in UK practice and it doesn't take a lot to really get this right. If you get it wrong, it can be very uncomfortable, it can very costly and very consuming. But getting it right just involves adhering to a few basic concepts and principles. But this is a condition that is very common. So in South Warwickshire, we serve a population of 300,000. We would expect there to be something like 2000C, 282Y homozygotes in our community.
So it is, you know, it's more prevalent than hepatitis C, it's more prevalent than hepatitis B, it's certainly more prevalent than all the autoimmune liver conditions added together.
And it's there in the community waiting to be diagnosed. And if you make the diagnosis and you make it confidently and accurately, patients thank you for being there. They thank you for the clarity that you bring to this issue.
And it's something that is eminently suitable for, you know, good, robust primary care management.
[00:34:28] Speaker A: Thank you, Jeremy. I'm feeling more energised and keen to go and find those patients with hereditary haemochromatosis. It feels slightly complex to begin with, but actually, when you break it down and discuss it as we have, it doesn't seem that difficult to test for and diagnose the condition. But clearly we need to just keep our radars open. So we're listening out for patients who might have this condition and just being really confident about knowing how to make that diagnosis.
We're now moving on to the final part of the episode, Jeremy, where I just ask you, what are your key take home messages for our audience?
[00:35:05] Speaker B: Well, I had a medical student with me in clinic yesterday and I said to her genuinely that, you know, most of us would recognize that the practice of medicine is actually quite easy. It's medical schools and hospitals that make things complicated.
So I think I would suggest that every clinician colleague enjoys the precious time they have with patients, but on the patient's behalf, listen to the concerns of the patient. And I think with regard to haemochromatosis, you know, be on, look for the opportunities to make an early but make an accurate diagnosis. And that's about using the laboratory evidence in a informed and careful way, because there is still a rosy glow to be gained from actually making a diagnosis. Whether you're in primary care, secondary care, you know, when it all comes together like you see in a textbook, there is still a certain joy to be had when actually the penny drops and you can say to a patient, I know what you've got. And this is all straightforward and we can manage this for you. And I don't think there's much more inducement I could really offer to other clinicians than doing the job and doing it well. And if as a special interest group we can help people do that and get it right more often than not, then we're very keen to work together.
[00:36:23] Speaker A: Well, thank you so much for speaking to me today, Jeremy. I found that a really interesting discussion. I'm sure that our audience will have learned an awful lot and hopefully will be feeling more enthusiastic and energised around this topic and keen to get out there and find patients with hereditary haemochromatosis. It's been an absolute pleasure, Jeremy, thank you for giving your time to the podcast.
[00:36:46] Speaker B: Well, Charlie, thank you for the opportunity and it's been a pleasure speaking to you.
[00:36:51] Speaker A: Well, that was a really comprehensive episode looking at iron overload. So much to take from that episode, looking at iron metabolism, the diagnosis of hereditary haemochromatosis and the treatment of it.
My key take homes were firstly iron testing, so understanding what a high ferritin level is. Jeremy was telling us that it was 250 to 350 or more and also understanding where transfer and saturation sits in all of this, because actually that can feel quite complicated and confusing. But actually transfer and saturation really is just telling us how much iron is circulating within the body and a level above 50% would be considered high.
Secondly, thinking about the common causes of raised ferritin, it was really interesting with Jeremy discussing that about 10% are caused by iron overload, I.e. hereditary haemochromatosis, whereas actually about 90% are caused by conditions that we commonly see in primary care, such as masld, otherwise previously known as non alcoholic fatty liver disease and alcohol related liver disease. So these are really common causes of raised ferritins, but not necessarily iron overload. So that's where we really have to understand where those tests come in, where we check the ferritin, where we check the transfer in saturation.
And then finally, it was really helpful and interesting talking about the treatment of hereditary haemochromatosis with venussection being the primary modality by which it's managed with that initiation period, that is multiple episodes of venesection to get that ferritin down to a safe level, which as Jeremy said, was between 50 and 100, and then after that, regular monitoring of the full blood count and periodic venous section longer term.
So thank you so much for listening. I hope you've enjoyed this episode. If you have click follow and you'll get every update whenever we bring out a new episode. We've got a large number of episodes available on the podcast and we always benefit from and really enjoy hearing your feedback. So please do feel free to leave some feedback on the podcast we or make contact with the Primary Care Society for Gastroenterology. Thank you very much.
