Alpha-1 Antitrypsin Deficiency: Bridging Care
Transcript: Hepatic manifestations in AATD
Carolin Schneider, MD
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- This is a finding that is also driving also my whole career trajectory actually, because I was a doctoral student with Professor Strnad, who's one of the leading experts in AATD, and I wanted to participate as part of the control cohort, but suddenly it turned out that I'm also an MZ carrier. And this led to a screening also in my family and also about me thinking what actually genetic screening means for a person. And yeah, I think this also shaped my career actually, because then I was also motivated from a personal standpoint to go deep into liver disease and how we can shift also the risk if you have a genetic mutation. I think of MZ mostly as a risk modifier. It's a genetic mutation that you have, but it's not as severe as a ZZ mutation. But obviously, I also advise patients to be very mindful with metabolic risk factors, particularly alcohol or obesity. So I see it more as a, risk modifier.
I think prevention is one of the main topics also for the years to come. And I think AATD and especially the MZ carriage is one of the building blocks of preventing liver disease. So to know what genetic risk you have and then how to modify it and hopefully to prevent the onset and also progression of liver diseases. I think this is where we are going. So I think this is one of the question that, also drives a lot of our current research because I think mostly of unexplained elevations of AST, ALT, or gamma GT that show no other signs of other liver diseases or if we see evidence of steatosis or also more advanced liver disease. I think it's always AATD is something that is underdiagnosed, but we should also work towards, and this is also something where this video is going to really increase the awareness that you should also test for AATD so that it's not overlooked. I think early interventions to reduce the progression before fibrosis or cirrhosis onset is also, again, part of this risk-modifying behavior. And I think we have two parts here.
One is the risk modification and the second one is really the surveillance to check regularly if liver disease has developed and if someone is a high-risk person, to then also increase the surveillance of the liver, particularly also with FibroScan, which is one of the assessments that is also recommended by current guidelines. And on the other hand, to really counsel on risk factors like alcohol, obesity, but also diabetes if it is present. We can reduce the risk of progression before it even starts. So this is also an answer of someone who works with the liver a lot. It is alcohol consumption that is one of the most important risk factors, and the second one is metabolic dysfunction. So I think these are the two that also in, counseling we prioritize most, and I'm especially involved in, also counseling on steatosis, but also giving advice on alcohol reduction, diabetes control, and also avoidance of any additional type of liver injury.
During my time in the research group of Professor Strnad, I was also involved in a population-based study with two cohorts, one that I was also in, and in that we collected in Aachen and one of the population-based cohort. And what we actually could find is that especially there's an interaction or an interplay between genotype, age, sex, and also co-factors, because we could show that, for example, male patients were more likely to develop liver disease, patients over the age of 50, and with obesity or diabetes.
So there is this interplay of these different factors to drive then also liver disease that we can use to counsel and also to prevent the onset and progression of liver disease. The barriers are mostly to find these patients, because if you start counseling on genetic risk, many people are afraid of passing a genetic condition on to their family, what this means for their offspring, for their children, for their grandchildren. So I think really being mindful when communicating about a genetic risk and what this means for liver disease is something I'm very passionate about. And the second thing is really to find those patients, especially those with MZ, and to also increase the awareness for liver disease, and especially those that are also partly driven by genetics. I think that's a really good question because early identification is such a big part of what could prevent the onset of liver disease.
And some people already did this, right? Developing guidelines on when to measure also AATD levels and also making it a core part of testing unexplained chronic liver disease or chronic elevations of ALT to really increase broader family testing if we identified a case and to also provide a lower threshold for genotyping, especially in steatotic or alcohol-related liver disease, I think that's a really good start. And then the second step is to really then get those patients towards a screening of liver disease, and the FibroScan is one of the main tools that should be used to also get a baseline of where this patient stands, and then also to include them into surveillance.
So the behavioral and cultural barriers that especially exist towards genetic testing make it hard to reach those patients which would also need it, because the risk of a genetic mutation might also feel invisible, and liver diseases can take a long time to develop. So to really explain the risk, how we can modify the risk today and what it means to detect it early, I think this is also where we should start.
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