Alpha-1 Antitrypsin Deficiency: Bridging Care
Transcript: Gastroenterology in AATD
Debbie Shawcross, BSc, MB.BS, PhD, FRCP
All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
- We most commonly see patients with alpha-1 antitrypsin deficiency in our chronic liver disease clinics or our hepatology clinics. And to give you a little bit of context around that, it's important to say that the alpha-1 antitrypsin deficiency, particularly in individuals who are carriers, so that means that they have one copy of the defective gene, it makes them more vulnerable to developing chronic liver disease. So, for example, if you are overweight and you have steatosis or fat in your liver, if you were to carry an alpha-1 antitrypsin gene, if you were a heterozygote, you are more likely to go on to develop a liver fibrosis or liver cirrhosis. Similarly, if you drink more alcohol than is advised, again, the alpha-1 antitrypsin will act as a co-factor, and that also applies to other more rarer types of liver disease.
So, what is a really, really important message for gastroenterologists and hepatologists is to be aware that it's often missed as a co-factor for driving liver disease. And it's important to think about it when you are seeing new patients in the clinic with chronic liver disease. In expert centers. So in expert liver centers, it's done routinely in new patients who present with new presentations of liver disease or chronic liver disease. But I think in centers where there's perhaps less experience when new patients present with chronic liver disease, sometimes it can be overlooked as something that's done in a routine liver screen. And I think, you know, it can be missed quite often. So in populations where you have a high proportion of individuals who have Celtic or Scandinavian backgrounds, so in the UK, for example, in Northern Europe, that's very common.
So one in 1,500 to 3,000 individuals can have the homozygous form of alpha-1 antitrypsin, and many more will carry the heterozygous form. And therefore, it's really, really important that in those populations, you think about alpha-1 antitrypsin routinely in your practice. In populations that have less dominance of Celtic or Scandinavian heritage, and particularly in Asian populations, it's much rarer. So it's possibly not the thing that people need to necessarily jump to, but what it's really, really important. It gets forgotten a lot, and it's really important to be aware. And it's important to be aware because, actually, if you know it's there, you can sort of more aggressively manage these patients because what you want to do at the end of the day is to prevent the development of liver disease, and you want to slow down the progression of liver disease. I think it's important to say that the majority of patients with alpha-1 antitrypsin deficiency are actually asymptomatic, largely. So they don't know that they have it. And so they may not have any symptoms at all. And that's really, really important. But also, you've got to think about the type, or the phenotype, of the alpha-1 antitrypsin because that's important in determining what symptoms might be. So if you carry the S gene, that's the gene that will lead to the development of lung disease and emphysema. And therefore, it's the most important thing there is about diagnosing individuals that may be breathless, may have asthma-type symptoms, may have early-onset emphysema, and having a recognition that perhaps this could be important, but also in individuals who are smoking, who may get accelerated lung disease.
So lung symptoms are important. So chronic cough, wheeze, shortness of breath are important. But also in the clinic from a more gastroenterology standpoint, individuals that carry the Z gene, the Z phenotype, they are at increased risk of developing chronic liver disease. And in many of those individuals, they may not have any symptoms at all. So they could be developing liver disease without even knowing about it, or if they have other co-factors, as I mentioned previously. So if they are overweight, if they are drinking or consuming too much alcohol, if they had hepatitis B or hepatitis C, or maybe an autoimmune liver disease, then having even one of the defective alpha-1 antitrypsin genes that can increase the likelihood of them going on to develop liver fibrosis and liver cirrhosis. So it's really, really important to pick these factors up. But I think an important message here is that actually, many patients may not have any symptoms at all, and that's why sometimes, as a diagnosis, it can be missed. What would normally prompt investigation is any presentation that may suggest an individual might be at risk or have underlying chronic liver disease. So it could be that when they see their primary care physicians or other physicians, that they may have risk factors for liver disease. So, as I've mentioned, viral hepatitis, alcohol, being overweight, and that should be a prompt to do a full liver assessment. But it could also be that a patient may present with deranged liver enzymes or actually more advanced liver disease. And in terms of a diagnostic pathway, we would always recommend that you do a non-invasive liver screen.
So what is a non-invasive liver screen? A non-invasive liver screen is basically doing a screen for all of the potential causes for chronic liver disease. So, apart from doing liver biochemistry, an assessment of liver synthetic function. So that might be clotting, albumin, bilirubin. You would also want to look to rule out other causes of liver disease. So you would want to rule out autoimmune liver disease. So, you want to do auto-antibodies or immunoglobulins. You would want to exclude hepatitis B and hepatitis C, and that's important that you screen patients for that and potentially some of the other rarer types of liver disease. And that would include measuring alpha-1 antitrypsin levels or, if possible, doing phenotyping, which means that you actually look for one of the alpha-1 antitrypsin defective genes. There are also a number of other quite rare liver diseases that are also common in the sort of Scandinavian and Celtic populations. And that would include conditions like hemochromatosis, which is basically a condition that causes iron overload, or even something like Wilson's disease, which is even rarer and associated with an inability to excrete copper from the gut and the liver. So you'd want to do that full non-invasive liver screen. You'd then want to go on and actually do more of an assessment to see if there's any evidence of liver damage. And one of the first things that we do in a liver clinic is to do an assessment, a non-invasive assessment of liver stiffness, and elastography is by far the most common way to do that. And you would use something like a FibroScan, where you would do an assessment not only of the amount of fat in the liver, but also the stiffness in the liver. And if you have an increased level of liver stiffness, that really raises awareness that there may be some underlying chronic liver disease that needs investigating further. We generally also perform a liver ultrasound in the clinic. And that's useful, particularly if you're looking for individuals who may have progressed to develop advanced liver disease, cirrhosis, or portal hypertension. But also, you can do an assessment, a relative assessment of steatosis on the ultrasound. And with those initial tests, you then make a reasonable assessment of the likelihood of whether that individual has significant liver disease. I'm also going to just raise that sometimes the question comes up as to whether a liver biopsy is relevant, and generally, for alpha-1 antitrypsin deficiency, we don't routinely do liver biopsies as a diagnosis. We do genotyping, and we do those kind of non-invasive assessments in the first instance. Communication between teams is absolutely imperative. So it's really, really important that you discuss patients. But it's interesting because generally patients will either have more of the respiratory phenotype, the S phenotype, or the Z, which is the liver.
So it may be that patients are predominantly cared for in a gastroenterology or a liver setting, or primarily managed in more of a respiratory clinic. And it's rare, actually, that the two overlap. However, you do sometimes find families, and actually, I'm gonna give you an example. I look after a family of parents and five siblings who have a combination of the M, the S, and the Z phenotypes. And for those individuals affected by the S phenotype, obviously, there are more concerns around respiratory symptoms and monitoring lung function, whereas those with more of the Z phenotype, it's more of a liver assessment. But it is not uncommon to have an individual who might have one S and one Z gene, which might mean that they can have a mixture of both respiratory and liver involvement. And therefore, it's really important that the respiratory, and the gastroenterology, and the hepatology doctors talk together. But there are, of course, more than 70 different types of defective alpha-1 antitrypsin genes. So often, you'll find that no one patient is the same in terms of how they present or the symptoms that they have. I think you always have to put the patient at the center of the care plan. They are the most important individual. And I think for me, it's about communicating the importance of preventing ongoing liver disease and slowing down any liver disease progression.
I've mentioned this already, but it's such an important point. So what it's really, really important to do is to communicate to the patients that they need to really modify things in their life that could expedite or speed up liver damage. So, for example, if you are a carrier of the Z gene, you know, you really need to watch how much alcohol you are drinking. So you would advise that you need to either abstain from alcohol completely in an ideal world or to limit the amount of alcohol that you drink. And that's a really, really important message to relay to patients in the clinic. Also, about managing weight as well. I think it's really underestimated the damage that being overweight and storing fat in your liver does; it causes inflammation and scarring over a number of years. And if you have alpha-1 antitrypsin deficiency and you have liver inflammation because you have excess fat stored in your liver, that again is something that can be modified. So it's awareness about managing the co-factors. You can't change what you're born with in terms of genes, but you can carefully manage the additional co-factors that put you at more risk of developing liver disease.
My top message is it has to be about increasing awareness. You know, so in European population, Scandinavian populations, alpha-1 antitrypsin deficiency is really common. And therefore, you have to really make sure that when you are seeing new patients in the clinic that you think about could they have alpha-1 antitrypsin disease or certainly be a carrier for it, and are they at increased risk of developing liver damage? So my number one message here is awareness to gastroenterologists and hepatologists, and clinicians as a whole, that it's important that you think about this. What could I change? Well, as I mentioned before, you can't change the genes that you're born with, not easily anyway. And therefore, what you need to do is work in a way that you prevent as much as you can disease. And I'm talking specifically about liver disease. So it goes back to making individuals aware that they need to look after themselves, they need to look after their livers. And that's also important, even if they don't have alpha-1 antitrypsin deficiency, they need to look after their livers. But specifically for individuals who are carriers or have the disease, they need to look after their livers, they need to abstain from alcohol, they need to watch their weight. And also, you know, think about other things that might put them at increased risk of getting liver disease. And this is really the most important take-home message. Please don't forget about it and how important it is.
This content has been developed independently by Medthority who previously received educational funding from Takeda in order to help provide its healthcare professional members with access to the highest quality medical and scientific information, education and associated relevant content.
Updates in your area
of interest
of interest
Articles your peers
are looking at
are looking at
Bookmarks
saved
saved
Days to your
next event
next event