#380 Hemochromatosis with Elliot Tapper

Paul I want to tell you a story about uh back when I was in high school uh you know my dad said to me Matt I think you have iron deficiency and I was like shut up Dad you're not a doctor and then he was like well Matt your shirt's wrinkled I feel like I don't really have to be here for these that was the end my delivery is terrible that was it the curb Snyder's podcast is for entertainment education and information purposes only and the Topic's discussed should not be used indices or conditions expressed on this podcast and affiliate Outreach programs if indeed there are any in fact there are none pretty much we aren't responsible you should always do your own homework foreign [Music] ERS I'm Dr Matthew watto here with my great friend and America's primary care doctor Dr Paul Nelson Williams Hi how are you doing today Paul I'm great Matt thanks for asking I felt very sincere I appreciate that well Paul I'm I'm doing very well because on tonight's show we have a fantastic returning guest Dr Elliot Tapper we're going to be talking about hemochromatosis a condition which Paul I thought I was going to diagnose it many times but I think uh I have yet to diagnose a case of hereditary hemochromatosis that was you know convincingly causing any significant disease but maybe maybe someday now that I know a little bit more what to look for uh Paul can you tell the audience what is it that we do on this show and then when you please introduce our wonderful co-host happy to uh on both counts Matt we are the internal medicine podcast we use expert interviews to bring you clinical pearls and practice changing knowledge as you mentioned we talked to the amazing Dr Elliot Tapper and we are lucky to be joined by Dr Elena Gibson uh producer co-host extraordinaire Asylum for much of this episode uh due to technical difficulties but there with this in spirit Elena how are you I'm Leslie I'm back returned wait I agree with both of those yeah so happy to be here we had a great conversation well mainly Paul and Matt but I was listening with Dr ellia Tapper he is a highly educational Twitter hepatologist if you want to check him out there who loves caring for people with livers studying people with livers and talking about the liver with whomever will listen so today that is us he lives in Michigan where he has a dream job and spends his free time shuttling his children between activities he is thrilled to be back on the curbsiders and we're happy to have him here and so tonight he teaches us all about hemochromatosis uh some good pearls to take away and that you'll learn more about include some potential mimics of hemochromatosis and the most common etiologies of an elevated ferritin and those include dismetabolic iron overload syndrome so that was a new term for us and then inflammation as well so tune in and a reminder that this and most episodes will be available for free CME credit for all health professionals through VCU Health at curbsideers.vcuhealth.org uh Elliot welcome back to the show so good to have you back your your last episode I don't want to embarrass you too much but it was one of the all-time uh top curbsiders episodes uh not surprisingly so welcome back a privilege to be back yeah I mean liver liver tests definitely one of the Banes of the primary care doctor having abnormal liver tests so people can go back and listen to that episode this one's going to build because we're now we're talking to be talking about you know one of the potential causes here so let's jump right into a case from cash lack Elena can you start us off yeah let's do this all right so we are seeing a 53 year old gentleman uh at Cash slack Memorial he has a history of diabetes obesity and prior alcohol use disorder who was recently hospitalized for abdominal pain he was ultimately diagnosed with ascites and received a new diagnosis of cirrhosis during his hospitalization a workup for the etiology of his cirrhosis occluded an iron panel to evaluate for hemochromatosis so thinking about hemochromatosis as a possible etiology of liver disease what is hemochromatosis and how common is it yeah it's a great thought because definitely hemochromatosis is is on the list of things that we know can cause cirrhosis so in general hemochromatosis is iron overload and it's hereditary hemochromatosis when the person has two copies of a mutated Gene that interfere with the normal cycle of iron absorption and feedback typically related to a mutation in hepsidin it essentially they have a disorder where they're never telling their body to stop absorbing dietary iron the iron is absorbed and where does it go it will go to the liver it will go to the joints to the heart to the pancreas to the skin but in this world where we have a lot of blood tests it's very rare to start seeing those classic things that we learned about in medical school like bronze diabetes typically people are going to show up with the most common manifestation of hereditary hemochromatosis which is liver disease can you remind people just a little bit about hepsidin why it's important with the I guess a little bit about iron absorption it might be might be useful to just talk briefly about how that happens in the body yeah so what what we know about iron absorption is that the it's happening in the proximal small intestine it's mainly because of a portal that will open up uh by way of ferroportin now the thing that controls ferroportin is hepsidin which is a hepatically synthesized protein and when your body when your bank of iron is is completely full then you have a very strong negative feedback loop that turns that hip side and activity off the difference in hemochromatosis is that there is nothing there to tell it to stop now you had earlier asked a question about how common this is and I think it's worth explaining that this mutation in hepsiden the most common one that we're seeing is the c2a2y these mutations are so common that about 1 in 240 Americans carry two copies of this autosomal recessive condition and it's it's geographically variable where actually the greatest density of mutations is in Ireland where eleven percent of the population is carrying at least one of these uh defective uh genes but you need two copies to have the genetic condition of hereditary hemochromatosis so Elliot for this patient in particular I feel like we have a lot of things to suspect about underlying liver disease already like we give you a history of underlying diabetes and this is a patient with obesity and then even some prior alcohol use thrown into the mix like I feel like we'd have some fairly good explanations for underlying cirrhosis I guess yeah but I do see that we test these patients fairly frequently so I'm wondering should all patients with chronic liver disease be screened for hemochromatosis even if we have some suspicion that something else might be going on or what what should be our general approach um in scenarios like this so I'm going to answer this by giving you a my Approach and and show you a little bit about how I think I would differ a little bit from some guidelines so I think in typically when you read a liver guideline from America or Europe they'll say once you've identified somebody with severe liver disease like cirrhosis you should screen for hemochromatosis but there's a variety of reasons why that's not a good idea in this case first this is a hospitalized patient who is ill for some reason and we know that iron indices are acute phase reactants and we're not going to get the most reliable tests for many patients in the hospital this is not the right time for this number two is that that is just a guideline and it's not based on any hard data and what we do know is that this man is presenting with two things that change the pre-test probability of hemochromatosis in incredibly important ways one he has obesity and diabetes raising the possibility of metabolism syndrome and Nash and two he has prior alcohol use disorder which is a much more common cause of liver disease than hemochromatosis and so I tend to want to use what the patient tells me and be guided by the history to have the best use of additional Laboratory Testing and for people like this who have given me a diagnosis in many ways I'm not going to reach for ferritins and iron and tibc in the first pass of my labs I like that because we we were talking ahead of time where some you know sometimes you see all the iron studies going in a certain direction and you start to think could this be hemochromatosis and it it's I think you could go down the the wrong path if you do that so it's it's good to know the setting of where we should do that like if you're so you're saying someone who's stable in the primary care clinic that would be a totally different mental calculus uh than the person that's acutely ill and hospitalized yeah definitely so if they're acutely ill I think most people would agree that this isn't the right time to go check in ferritons but even in the Outpatient Clinic it's important to spend the limited time that we have with patients focusing on the on the most impact that we can have on their lives at that time while we're diagnosing liver disease we're talking about the alcohol or the Obesity the diabetes the metabolic syndrome that is most likely triggering these things because bound up in all this discussion is really that there's a differential diagnosis for an elevated ferritin an elevated transference saturation and perhaps we can get to that yeah I think let's do it so what are you thinking about in the in the hospital in a patient like let's just say in the hospital what are you thinking about when you see an elevated ferritin and you can qualify that if you want to put certain cutoffs that make you think different ways okay so after 10 000 then we're not even thinking about the liver we're thinking about zebras we're thinking about severe sepsis severe inflammation hemophegocytic lymphohistiocytosis uh adult Stills things that uh are the stuff of morning report after a uh if someone comes in with a with like over 300 500 that's just a hospitalized patient as far as far as I can tell when you're over a thousand that's still telling me that they have a severe uh inflammatory condition I'm still not thinking about hemochromatosis it's just that the in this case if you're several logs above uh normal then you're thinking that this person could have a special set of severe illnesses just none of them are liver diseases so so basically in the hospital again this just tells us that most a lot of the patients coming in the hospital acutely ill they're inflamed ferritin's in acute phase reactant so it's going to be up and you know and then I think to add complexity to that I always think a lot of our hospitalized patients are sick and inflamed but they're also bleeding so then it's like how do you interpret the ferritin is it like does it look kind of normal because they're bleeding but it's really it would be high if they weren't bleeding all those all those sort of things anything else you're looking at in the um in the in the panel like the in the liver tests or in the CBC when you're when you're considering a diagnosis of hemochromatosis so when considering a diagnosis of hemochromatosis the two critical indices are one ferritin which is going to be elevated and two transferrin saturation and the cutoff here and this is this is based on iron divided by tibc sometimes the lab will give you transferrent saturation but once you get those numbers if it's greater than 45 percent you start to worry about hemochromatosis you'll see greater than 50 percent for men but if you can only remember one number let's go with 45 percent when I look at the CBC and the liver enzymes I'm mainly using this to start calculating in my mind the probability of cirrhosis is the AST greater than the alt has the platelet count drop below 150 below 100 I'm starting to think is the game afoot in terms of severe liver disease for this patient it helps me prioritize how important it is to come up with a firm diagnosis for them as well and one other thing I wanted to ask you about because I hadn't been trained to look at this the I think it was the RBC volume is that what it was the that they were talking about above a certain cut off might might tip you in one direction do you pay much attention to that so I think that this is one of these things that has stuck around for a while where you will see changes in MCV that are are that were classically associated with hemochromatosis but red cell indices are neither sensitive nor specific for the kind of thing that we're hunting for particularly in the outpatient clinic setting okay so stick to ferritin and transparent saturation and then when we're looking at the CBC and the liver tests we're just sort of keying in could this person have cirrhosis I like I like it Paul I see you you look very pensive I know you have something to say yeah I don't I feel like I just I I I feel kind of at Sea here the opposite of uwato where you're like you're it seems like you're always wondering could this be hemochromatosis I'm reading through the pre-reading I'm like oh God have I missed hemochromatosis 37 000 times then these indices are often kind of muddled and often so many of our patients have predisposing factors that could sort of be other causes of abnormal liver enzymes and they'll be different and that kind of stuff I guess I what I'm wondering I guess is there any particular patient or phenotype like that is like slam dunk home run where you think well this is someone I need to test for humanchromatosis or like what before you even get Labs is there something that raises your clinical suspicion for it or is it just one of those things that you do for completion's sake yeah so I am more likely in the first visit to check iron indices in somebody who lacks classic risk factors for what is best described as dismetabolic iron overload syndrome so people who I know are not drinking I have biomarkers that prove they're not drinking alcohol to excess I know that this person doesn't have diabetes or severe metabolic syndrome but if I have mildly elevated liver enzymes I'm going to focus on global Liver Health and lifestyle changes in hopes that I can improve those liver enzymes and I use time to be the greatest Arbiter of the diagnosis where if that person stops drinking or Cuts back or if they lose weight and they still do not drop their alt or Do not drop their ferritin then I start to look into it a little more closely but I have seen over the course of six 12 months people take ferritins in the low thousands to the low hundreds simply with lifestyle change validating this approach because common things being common the mo it's much more likely that their elevated ferritin is going to be caused by the dismetabolic iron overload syndrome do we understand why that happens why the person with chronic liver disease or metabolic syndrome has might have elevated ferritin levels is that I I don't that doesn't doesn't quite make sense to me or is it just inflammation yeah I will I will accept that one word answer okay so one in three people with non-alcoholic stiato hepatitis Nash are going to have iron overload if you stain their liver biopsies you will find iron there and there's probably two reasons for this in Nash one is chronic inflammation will influence the way that hepsidin behaves in the liver and then two inflammation of the hepatocyte is bursting open these cells spilling their contents into the blood uh and among them ferritin so you will see Iron and ferritin as a function of liver cell death but two out of every three people with alcohol-related liver disease will have elevated ferritin and there are at least three reasons there there's the inflammation there's the hepatocyte cell death and then there's the fact that alcohol is itself a influence on hepsiden it will increase hepatitin activity almost like it's been mutated so you can see in people with alcohol use disorder not only elevated uh ferritin but also transparent saturation now you're not going to see transference saturation elevated in every single person with alcohol-related liver disease but you're going to see it a lot more commonly in people with ald than those with Nash so back to our case here we have this 53 year old as we said diabetes obesity she has alcohol use disorder and uh we're we're doing our basic Labs on her so the iron studies come back uh her ferritin is 1667. her iron level is 170. the tibc is 203 and that makes a transfer in saturation of 84 percent what do you what do you think about these results for this patient and again this is a patient who's hospitalized right now for abdominal pain and she's got new ascites and cirrhosis well obviously we've addressed the idea that these these these Labs can be affected in the acute setting but if we come back to the basics about diagnosing hemochromatosis if you have an elevated ferritin and by that I mean a ferritin greater than 200 for women 300 for men and you have this transparent saturation that's greater than 45 50 then the probability that this person has hemochromatosis is much higher so if I was handed these Labs I would say yeah hemochromatosis is on the list but there's two problems one is that there are things that can influence transference saturation like alcohol or genetic hemochromatosis and then there are things that can influence the ferritin the acute phase of things so you can have the genetic condition but it might not be penetrant so in people with genetic hemochromatosis you will always see this elevated transference saturation but you don't necessarily ever develop the iron overload and this is probably a good time to mention you had um I guess on Twitter posted I can't remember how long ago this was but there was this Jama Internal Medicine article in 2017 by odafalu and this was a case uh similar it was a it was a patient who drank alcohol they didn't really clarify how much they had elevated ferritin and transfer and saturation they ended up testing the patient for hemochromatosis and do you want to talk a little bit about what the Miss what the pitfall was in that case because it kind of relates to what we're getting at here yeah it was a great case that's a shout out to gem internal medicine and the teachable moments series a lot of great stuff in there so what happened here is that by by focusing on the stuff that we can diagnose by the by the orders that we can check off in Epic we focused on the positive hfe gene mutations that you could find in in the blood and so because we had a positive diagnosis from Labs we anchored on the probability that it was the hemochromatosis that was driving the elevated ferritin and when you see that you're going to respond if you you'll respond to it by ordering phlebotomy in this case the patient actually had elevated ferritin and probably anemia caused by alcohol use disorder which was hinted at in the history but forgotten when the blood test came back they proceeded to get phlebotomies syncopized and then were lost to follow-up because of their reactions with their interactions with the healthcare setting so the the key lesson here is that although hemochromatosis mutations are so common they're actual penetrance is very low it can be as low as one in a hundred so about one in every 200 people have the copies of the genes but one in every hundred of those people will actually have penetrant disease now it could be higher than one in a hundred so in some series it's about 14 and 100 women 24 and 100 men but what we're talking about for penetrance there is that a doctor gave them the ICD-10 code for hemochromatosis so it could just be that they were responding to it but in terms of actual iron overload it's not a guarantee that these genes will result in that so you still have to deal with the common problem of alcohol use disorder which was missed here yeah and this case was I think particularly because they could have addressed the alcohol to use disorder a couple years sooner and I think the way they eventually figured it out was she that she eventually presented with like cirrhosis and they realized that the the alcohol was causing the high ferritin so yeah so sad case so hopefully the audience won't won't miss that now that we're we're highlighting on on this episode and I think we've we've talked a little bit about like some of the mimics of hemochromatosis here so if we what would be a good way to approach a patient like this would we would you let them kind of cool off for a while see them back in clinic maybe if they'd stop drinking how long would you wait before you would repeat the labs in someone yeah when you're a hepatologist like me who says things that are a little bit against the grain of guidelines that means that you're on the hook to follow people longitudinally to make sure that you are uh you're you're taking care to follow your diagnoses through so this is super common for me we we have a meeting we talk about a plan and then depending on how ill they are the severity of their Baseline disease will craft how frequently we have to follow things but I'll be checking the labs every three to six months there's no urgency to uh to uh to immediately phlebotomize the patient if they stop drinking if they lose weight their ferritin will come down phlebotomy or not um Paul any other specific questions about this case I know we I know we have another one to go to get get more into the into the primary care Realm um not about this case in particular I yeah I just I wonder if it's not worth reviewing some of the other manifestations I know that we're focusing on the liver which is probably the appropriate thing but just in terms of we are talking sort of offline about how often do you see like arthritis I just don't even know what to do with I think I saw the numbers like 24 of patients with the diagnosis have arthritis but I'm not even sure how much that differs from just the population without so I guess I'm wondering you know are there any other sort of characteristics other than sort of the liver dysfunction that you you typically see or is there a fairly wide spectrum of disease it's quite complicated because I really do think that the availability of blood testing has changed the presentation of this condition in such a dramatic way that we're now diagnosing it way before it would have been in the days of your so you're never going to see somebody with bronze diabetes and then arthritis is so common right I I it is definitely more common in people with hfe gene mutations but I I I I don't know how much more whether that changes things I think that you tend to see more in the in the form of uh cardiomyopathy diastolic CHF at least in my clinic I I'm not sure how true that Association has so if I were to paint a a general picture that is roughly accurate it's basically turbo metabolic syndrome all of the complications all of the various comorbidities just slightly worse in people with hemochromatosis yeah I'd buy that because it just it seems like you could see it everywhere if you were because like what are the manifestations you know elevated liver enzymes arthritis I was in clinic today almost everybody had metabolic syndrome that I saw right yeah or it was or drank heavy alcohol so I probably could have seen it everywhere today let's say this person wasn't going to practice your style and they the the people get these Labs back they're like tsat above 45 percent and uh you know the ferritin is 1600 I'm gonna just order the gene testing What gene testing would they look for and you told us a little bit about how you'd interpret it what what specific um mutations are there and I know there's some like off-brand mutations that's how I'll call them that that we might think about as well okay very good question when you order this test commercially it will be sent to a lab that will use probes for the c28 watt 2y and h36d genes um and and then you'll hear this story about header compound heterozygosity where one person will have one of the copies of one of the one of their hfe genes will be mutated c2a2 Y and the other H 360. and those people may be that may tend toward liver disease but it's it's always milder and the data is so much more conflicting so the mutations that really matter is that c2a2y then if you have a patient who has super high iron their liver is full of iron It Shines on an MRI but they don't have these genes and they have a low or normal transferrin saturation then very rare early those people can have mutations in ferroportin I have never diagnosed that okay probably so so probably probably Paul and I won't be diagnosing that more than enough we're lucky you mentioned the imaging test what so if this if this patient bill that we were talking about if if he had um heterozyg if he was heterozygous for the c2a2y um in just heterozygous would you sort of stop there and say okay this is probably just your the alcohol the metabolic syndrome the liver disease we don't need to do any further testing we don't need to get an MRI and look for iron in your liver well it's I love that you brought this up but let's just say that is where I would stop but let's just say that he comes back a year because you repeat his labs and the ferritin is worse the liver enzymes are worse and in this case I need to try to sort out does this man actually have iron overload and in in the olden times we would have to stab him in the liver and then burn the tissue to look for how much iron was there and nobody wants to have a diagnostic liver biopsy if they can avoid it and now the non-invasive method is to use an MRI an MRI will basically have a very hard time seeing the liver because of its paramagnetic properties and even though iron would would mess up the MRI generally in this case we're using it to make the diagnosis if you have a very bright liver looking for iron then you have proven that your patient has iron overload if there is iron in both the liver and the spleen you know that it's a secondary cause of overload because the iron is being deposited in endothelial cells because of excess transfusions and so forth or if there's no iron at all you know that this person doesn't have deposition of the iron it's not hemochromatosis primary hereditary or secondary right so hemochromatosis meaning hemochromatosis as you said to start this off is just iron overload we were talking about the hereditary version that's the kind that we were talking about with the genetic testing but even if someone doesn't have the home isn't homozygous for hereditary hemochromatosis just from chronic alcohol other from chronic alcohol use they could potentially build up enough iron that you could see it in their liver on an MRI yeah uh you you might be able to uh typically what what you'll see is fine amounts of iron that are can be stained on the liver biopsy if if you're getting very scientific about it yeah but severe amounts of uh of iron in the liver you're typically going to see from hereditary hemochromatosis or other secondary sources of iron overload okay so that would be like your transfusion for somebody okay yeah and that so it the it's and in those States it's more likely to be pathologic and you would worry about that iron causing liver failure if they didn't have it already and with these do these piece do people with transfusion Associated hemochromatosis also get like the arthritis and some of those other complications too or is that more which is the hereditary type you know I don't know the answer to that but I assume that they they they could I mean the secondary hemochromatosis can mess up a liver just as badly if not worse than uh primary hemochromatosis and they can also get significant heart heart injury so uh the management is usually more complicated owing to the uh comorbidities associated with those with uh with the the reasons for the iron overload in that setting uh but um I I I'm not sure about the whole spectrum of uh presentations okay so I guess to to conclude this first case we decided that this patient didn't have hereditary hemochromatosis patient uh went to see America's primary care doctor Dr Paul Williams and uh we got him we got him treated for alcohol use disorder stop drinking iron levels got better and uh the serosis stabilized so um as happy of an ending as it could be maybe and then Paul got him listed for transplant too didn't you Paul I mean sure why wouldn't I all right let's let's go on to the second case Paul would you do the honors sure we're moving on to Francesca who is a 51 year old female with a history of celiac disease who's presenting for her annual visit She was recently tested for hemochromatosis due to a positive family history and her brother and was found to have a p c 282 Y homozygosity and I'm sorry if I said those numbers in a weird way but that's what we're stuck with your labs are notable for a ferritin of 278 a tsat of 59 and an LED hemoglobin of 15.1 um and so I I guess the the follow-up question is we're sort of in different territory now so how is this case markedly different and sort of what what are the potential complications here as as opposed um yeah so let's actually let's just stop right there one of the potential complications we might be on the lookout for yeah so this is a a a a person who now is starting to fit the bill of someone where if these were the only numbers that I got I would be worried about uh genetic and partially penetrant uh hemochromatosis she has a ferritin greater than 200 she's also coming at me as a woman with a history of a disease that is associated with iron deficiency so I have a feeling that you know that she uh has this ferritin has fought against Great odds uh so uh so I I I'm a little bit nervous already but the ferritin although it couldn't be diagnostic of hemochromatosis it's typically the case that when it is less than a thousand there's a higher likelihood that they have not developed cirrhosis so back when we were trying to be very sparing with whom we would biopsy we would actually wait until the ferritin was greater than a thousand before deciding to biopsy to rule out sir Rosas and it is true that if you present with hemochromatosis in a ferritin of a thousand you're much more likely to have underlying cirrhosis so my gut sense is that this is somebody who is about to get diagnosed with hemochromatosis but we're going to have a a much more laid-back discussion about it what would your Spiel be like for this for this patient um how would you how would you explain it and what what she might expect going forward if if we were to find that yeah the first thing I would do is start drawing out the Cascade from hip side into Fair report and in the gym but I mean at the end of the day I I think this person would be able to understand that their body is very hungry uh for iron and that it's dumping it in the liver and that when you start to dump extra toxins into the liver it has the capacity to cause uh inflammation which I like into something like burning your skin and if you burn your skin it can cause damage the redness or inflammation will eventually go away and can be left with a scar and that same process can be occurring in the liver and so the two main objectives that I have in clinic today are to talk about one how I can reduce the odds that she'll develop inflammation or scar formation and two be able to tell her perhaps even today how much Scar Tissue she has in her liver so that she can know about her overall Liver Health and the need to do other things like screening for liver cancer and so forth so what testing might you order as a follow-up to this because we have these we have these basic Baseline Labs from from Paul Paul is referring her over to you because he had the same Gestalt so exactly how this would go down yeah so this feels great foreign so I mean this is a good set of labs I mean if I was seeing somebody like this and I didn't know their liver enzymes I would go get their liver enzymes if I had their liver enzymes and they were elevated you know I would ask about alcohol I would consider checking a phosphatidyl ethanol or pep level which is a test that is really revolutionized my practice I always tell people that I am going to be looking for a biomarker that tells me how much alcohol that they've been consuming over the last three weeks I don't try to do this as a gotcha and anyone who walks into my clinic who hasn't been checked for hip C or have B is going to but that's just to to round things out beyond that diagnostic part the prognostic information that I'll get you can get in clinic by calculating something like the fib4 which is based on the platelets the AST and the alt but in my clinic I'll be using fibroscan which has functionally replaced liver biopsy in this setting so I don't need a liver biopsy to tell me if there's iron in this person I've got hfvg mutations in a positive transference saturation and elevated ferritin you don't even need an MRI you know that they have a risk for hemochromatosis and then I use my fiber scan to tell me about how what the risk of cirrhosis is in this clinic today so you mentioned no MRI why wouldn't you want an MRI in this case or what what sort of case would you find the MRI helpful is it important to quantify like how much iron is in the liver if if you're testing like if you do the FIB four or you do the elastography and you're worried okay this person has advanced fibrosis um do you even need to do any further testing yeah so in this case if we don't have any other competing diagnoses that could be manifesting in part as this dismetabolic iron overload syndrome then I would feel comfortable and guidelines would allow me the privilege of providing this diagnosis face to face without any additional testing like MRI but where the diagnosis is in question or there are competing probabilities and you need to know if the if there is iron in the liver to to provide this person with the Positive diagnosis of hemochromatosis then you will go to that MRI and the once I know that they have advanced fibrosis or cirrhosis based on the fibroscan and after my limited laboratory evaluation I'm done I can tell them everything that they need to know about how Clinic with me is going to go on a semi-annual basis people with hemochromatosis Who present like this who who is otherwise asymptomatic if they have cirrhosis they're at increased risk of developing liver cancer that that risk will decline if we can remove the iron from their blood and get them down to a ferritin of like 50 but it will never go away that leads into some nice question about concretely sort of what does management look like from here and obviously you know the broader answer is it depends but it sounds like it's mostly kind of I'm not sure this is the right term like liver preservation that protection from viruses minimization of sort of toxic exposure that kind of thing but when when are you pulling the trigone phlebotomy and is there anything else that you're sort of in your momentarium to like I guess when you're making these decisions and what what guides sort of what happens next yeah so this is the key Branch point is cirrhosis or no cirrhosis once you're in cirrhosis you get that whole package where we start to think about liver cancer screening screening for varices like you said General liver care make sure that they're vaccinated against hepatitis A Hepatitis B and then we'll and then we'll talk about phlebotomy but the sort of general practice that anybody has for someone with hemochromatosis is to tell them to if they're taking a multivitamin make sure there's no iron in it to try to to try to keep cut back on things like red meat and then three because people with high transference saturations are at high risk of getting serious invasive infections from uh bacteria that require transferrin to get the iron for their own metabolism like vibrio vulnificus we tell all people like this to avoid the coastal Waters in the spring and summer as well as to avoid eating uncooked or raw shellfish-like oysters so when it comes to phlebotomy the goal is to get that ferritin to 50 to 100 that's our goal and typically I'll make a decision about how fast I want to get there based on how robust the patient is so if they come to me with a ferritin of a thousand and they're 36 years old and I I'll just we'll do phlebotomy once every week or two weeks until we get down to a that that low ferritin if I'm a little bit worried about them I'll space it out and sometimes what I'll find when I'm doing phlebotomy is that the ferritin will plummet very quickly and in that case I've actually learned that the person probably didn't have penetrant hemochromatosis in the first place I was probably phlebotomizing Nash which is something that a lot of people will have done so if you can if you can normalize a very high ferritin very quickly uh you're you're probably putting that person at risk of iron deficiency anemia even with a high ferritin and you can start to see that as the iron the transference saturation will start to plummet and the iron will be very low so it there's no hard and fast rule about how many units of blood need to come out before that person will normalize but if you watch the kinetics for your given patient you can get a better sense of what their total iron stores are and what the underlying biology that drove their presentation in the first place was I'm curious I I met a patient with uh hemochromatosis once that told me that they when they drank alcohol they felt bad and that when they donated blood they felt very good and they weren't in a formal they didn't have someone like yourself like following them they were kind of uh just kind of on their own going for phlebotomy the self titrating their ferritin I was trying yeah I I tried to convince uh them to go to see hematology to get some official you know someone someone actually doing this in a systematic way okay so I have heard this story several times myself and um I have learned the hard way to never take a placebo effect away from a patient you don't like you so um some people get kind of hooked on the uh phlebotomy even the people who don't have penetrant hemochromatosis will still like to go give blood and if they are giving the blood to the Red Cross then that is phenomenal it's very hard when I will like somebody will retire and then they'll they'll come to see me and then I'll say I'm not sure that you need phlebotomy because you went six months and your ferritin went from 50 to 45 so I'm not sure I'm not sure and then they'll get upset but like I need my phlebotomy I feel so much better so in in this case I've definitely seen that I cannot fully explain it um but we also pump it up for the patient that it's good for them so um I don't know where it starts for anybody but I am not one to question that all right okay so this this I it the person was very convincing and I was like I look if it feels good good you know then I I would just have someone check your levels make sure you're not like gonna become anemic from from this so it's always great Primary Care Counseling so it feels good you should be doing it just keep it up I really like it when people are in maintenance phase to if that if they can give their blood there's something profoundly sad about doing it in the uh farisa Center and we just throw the blood away and there was for a time a kind of stigma from the Red Cross about whether or not it was okay to donate blood if you had hemochromatosis I'm not sure why they were saying that I know that they don't want to be serving as like providing a medical service but for patients who are in the maintenance phase where they might only need to do a phlebotomy a few times a year uh this is the perfect opportunity to make a count twice love that that's great all right Elliot and uh we're we're running down to the wire here but I did want to ask about because I I had seen this our first case bill was a was a man that we gave you and in this case Francesca this is a female what what are the sex differences if any or in patients uh hemochromatosis can you speak to that a little bit well I think there's two ways of looking at this and the first is epidemiologically and it is that men are more likely to present with severe uh iron overload that the penetrance of this condition is higher in men and then the other thing is that they're going to present at an earlier age because their cumulative exposure to iron is higher because in contrast women uh uh are uh more likely to have menstruation through a large part of their life which is a effectively preventing that that iron overload this is modified by a variety of things Behavior environmental exposures that may have led to men being more classically Associated iron overload alcohol or obesity in those studies from from times in the past and nowadays I'm more likely to make a diagnosis of penetrant hemochromatosis in a younger woman even in her 20s because patterns of birth control have changed such that there's now continuous forms like iuds or oral contraceptives without interruption that result in a cessation of menstruation for many many years and so you're much more likely to pick up an elevated ferritin and younger woman now so a lot of these sex differences might be rooted in just differing Trends secular Trends it is probably more likely that there's differences in cancer risk that you might pick up but I'm not sure how solid those associations are so probably two more questions here and I I think anytime anyone gets a genetic test it's it can always be a little scary or if somebody's family member got a genetic test and you you're operating for incomplete information you know someone says oh my my family member has it maybe the family member was heterozygous or maybe the patient was heterozygous and they just see that they have the gene so now they're telling people they have hemochromatosis how do you sort that out or how do you talk to the patient about about that so the issue here is that we rarely have perfect information about what our patient has heard about their loved ones uh genetic history and responding to that I think our society guidelines tend to say if you have diagnosed hemochromatosis then recommend that first degree relatives be tested but we know that this is an autosomal recessive condition and that it is variably penetrant so our responsibility to is to tell people that that not everyone in their family is going to end up with this disease it does not affect it should not affect anything like Family Planning and that people with one copy of this genetic condition are not likely to present with any uh any disease I like it Elliot last last question here is in primary care I find that I I tend to get the person and you told us this great term dismetabolic Iron overload so now that I know that I feel like I have a better handle of what's probably going on but I tend to get these people who have either a high ferritin let's say 500 or above or or they have a high just randomly transferring saturation in the 40 to 50 percent range and I'm just like is this hemochromatosis how should I follow this up how would you handle that if you were Us in Primary Care so I think there's at least a couple of considerations the first is whether you think that this is a touchstone for you to help counsel your patient if they can see that this ferritin reflects inflammation and that what's happening with that iron is that it is effectively kindling for the fire that is going on in their liver or their heart or their joints and that if they improve their underlying health they can cool that fire off then that's great but not everybody responds to blood tests in that kind of productive way so you might be stuck thinking about when is the threshold where you're no longer comfortable just watching or forgetting about it and you have to consult hepatology and if you watch it for a couple of years and you watch it go up to 600 700 800 then I'm not going to be mad at you give me a call right and here at Cash like hospital we are we we we we are there for each other and um if you've watched someone's ferritin go up this is probably somebody with severely inflammatory liver disease more more often than not so it actually brings up a sidebar here which is that if Nash is the most common thing that is driving this and the ferritin is a sign of the inflammation and that there's actual iron being deposited in the liver it might be the case that if we lowered that ferritin if we lowered that iron there'd be less kindling for the liver fire there's actually been a randomized trial of Phlebotomy in just this patient by atoms at all and we're talking about people with ferritins of like 400 or so not the greater than a thousand and drum roll it made no difference to the patient's liver enzymes or or their or their liver histology so it would have been awesome but uh unfortunately I'm super glad they did that study because we see this all of the time but the ferritin will come down if they lose weight or stop drinking and so forth so it is still a reliable biomarker of Liver Health in this case okay so I can add this to my my metabolic syndrome checklist when I tell patients they're you know because I I do think it's helpful to say to patients you know they're saying am I am I sick from my obesity and I'm like well let's let's go through the checklist and now this is going to be on there with diabetes and blood pressure and sleep apnea all the all the other ones I I take off on there so great well I think at some point we have to let you go uh certainly it's a it's a what is it a Wednesday night Paul it's Wednesday night I'm sure you have better things to do so thank you so much for your time uh well let's let's get some take-home points here well if if people had to remember just like two or three things about this discussion what what would they be well for me the most common causes of an elevated ferritin are still going to be alcohol use disorder and metabolic syndrome slash Nash and then if you want to diagnose hemochromatosis you're looking for significantly elevated ferritin and the elevated transference saturation greater than 45 for women greater than 50 percent for men and finally that although this is a super common genetic condition perhaps the most common autosomal recessive genetic condition its penetrance is low somewhere between somewhere around 10 percent beautiful yeah thank you that's helpful always great to hang out with you a big fan of your Twitter even though I'm not on Twitter that much anymore uh I do I always enjoy reading your tutorials whenever whenever I'm on there and uh that's it we'll let you get on with the rest of your evening thank you so much thanks for having me guys this has been another episode of the curbside is bringing you a little knowledge food for your brain hole yummy we know it was you you get your show notes at the curbside.com and while you're there side for our mailing list to get our weekly show notes in your inbox plus twice each month you'll get our curbside's digest which Recaps the latest practice changing articles guidelines and news in Internal Medicine and we're committed to high value practice changing knowledge and to do that we want your feedback so please subscribe rate and review the show on Apple podcasts or on Spotify you can also send an email to ask curbsideers gmail.com reminder that this and most episodes are available through VCU Health at curbsides.vcuhealth.org for free CME and a special thanks to our writer and producer for this episode Dr Elena Gibson and to our whole team uh technical production is done by pod paste uh Elizabeth Proto and Jen watto run our social media and Stuart Brigham composed our theme music and so with all that until next time I've been Dr Matthew Frank watto Elena Gibson here good night and as always our main Dr Paul Nelson Williams thank you and goodbye [Music] [Applause]

Channel: The Curbsiders Internal Medicine Podcast

Views: 2,832

Keywords: Internal Medicine, Education, Curbsiders, Hemochromatosis, iron, liver disease, genetic, hereditary, iron overload, transferrin saturation, ferritin, primary care, assistant, care, doctor, education, family, FOAM, FOAMim, FOAMed, health, hospitalist, hospital, internal, internist, meded, medical, medicine, nurse, practitioner, professional, primary, physician, resident, student

Id: Szjiwd4LXYg

Length: 54min 15sec (3255 seconds)

Published: Mon Feb 06 2023