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24 - Noninvasive biomarkers for MASLD: FIB4 and ELF (16 min)
00:16:32
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- [00:00]
A
Foreign welcome to Healthier World with Quest Diagnostics. Our goal is to prompt action from insight as we keep you up to date on current clinical and diagnostic topics in cardiovascular, metabolic, endocrine and wellness medicine. When we talk about insulin resistance, most people think about blood sugar and diabetes. But what's less commonly recognized is that insulin resistance can manifest in the liver. That's the reality of masld, or Metabolic Dysfunction Associated Steatotic liver disease, a condition that is increasingly understood as the liver's response to systemic metabolic dysfunction. It's more than just fat in the liver. MASLD reflects deep metabolic imbalances tied to obesity, type 2 diabetes, hypertension, and cardiovascular disease. And the recognition for MAZLD is growing. Approximately 1/3 of the population has MASLD. With liver disease on the rise and early stages often going undetected, it's time we drill down into the disease to better understand it. I have here with me today Andy Hunt, product manager for the cardiometabolic, endocrine and wellness segment with Quest Diagnostics. And today we're going to start by asking the fundamental questions. First, what exactly does the liver do and why should we care about it?
- [01:23]
B
Yeah, well, we should care about the liver quite a bit. The liver, quite frankly, is really the workhorse of our body and it just doesn't really get enough love. Unfortunately, one in three adults worldwide are affected by fatty liver disease and most are unaware that they even have it. The liver plays really key roles in blood filtration, detoxifying, even plays roles in nutrient and hormone metabolism and is a key organ for energy storage. It holds on to all of our glycogen. And when we're in a case of low blood sugar, it metabolizes that glycogen into glucose and sends it out to the cells to be able to properly function. It also plays a role in our digestive system, in the world of bile production, and helps metabolize our fats in our GI tract. In reality, it has a role in all things metabolism. And as a society, myself included, we're kind of mean to our liver. I could say I was pretty mean to the liver most of my 20s. And if you partner some of our lifestyle decisions of adding diets full of sugars and processed fats, and you partner that with even what's out of our control, with this big world of environmental toxins creating this really backlog in our liver and again, overworking one of these organs that's already one of our workhorses. But luckily, we're starting to see the liver get a little Bit more love. There have been advancements in treatment therapies that really can help treat some of these severe patients with advanced fibrosis, as well as medical organizations like the American association of Clinical Endocrinology, the American association on the Study of Liver Disease, as well as the American Diabetes association all have different guidelines and have been really focused on driving awareness of this key disease and how we can look at treating the liver better.
- [03:08]
A
So true. Actually, I love that point. Historically, we have been pretty hard on our liver and we expect it to handle everything, right, from poor diet to medications to metabolic stress to the alcohol we might consume. But that's all starting to change, right? As you mentioned, in the past several years, we're starting to see a growing recognition from medical societies not just about the importance of liver health, but also about its role as a metabolic organ. And one of the biggest shifts that we've seen in recent years is a shift in terminology from non alcoholic fatty liver disease to masold or metabolic dysfunction associated steatotic liver disease. This change goes well beyond just renaming the condition, but it reframes how we understand it. It places the focus squarely on metabolic dysfunction as the root cause of the disease. Can you speak a little bit about why this change matters and what it tells us about how medical communities are rethinking liver disease?
- [04:05]
B
Yeah, absolutely. And luckily the medical organization saw the need for that, as historically it was known as non alcoholic fatty liver disease. And I felt like when you didn't get it, there was an excitement because maybe the alcohol didn't affect it. As we all know, unfortunately, that has its own role in driving inflammation and creating that stress on the liver with some of those detoxification pathways. But recently it's been changed to metabolic dysfunction associated steatotic liver disease. And that's really important. And why I want to highlight the metabolic dysfunction piece of that is because it's really some of our malfunctioning metabolic processes due to insulin resistance due to other cardiometabolic comorbidities that are really driving some of the fibrosis we're starting to see in the liver. And the truth is, we see metabolic dysfunction present itself in a lot of different diseases, unfortunately. But the one thing they have in common is the earlier we can catch it, the better we have a chance of making a difference in fighting some of these diseases.
- [05:08]
A
Yeah, and I think we speak to that a lot in the different podcasts that we cover here on Healthier World when we talk about cardiometabolic conditions and the importance of capturing Risk early when behavioral change can actually reverse the disease state. Now, in a patient with mass old, the fat and inflammation that accumulate in the liver eventually cause scarring or fibrosis and that impacts the ability for the liver to function properly. So when you're screening for liver disease risk, the first step is the Fib 4 Score or the Fibrosis 4 Score, which evaluates the risk for having advanced fibrosis. So let's first talk about the Fib 4 and how we can utilize it as a screening tool for masld.
- [05:49]
B
Yeah, absolutely. And there's really no easier and cheaper tool than Fib4. It is really created from analyze commonly being ordered in every healthcare visit from a CMP and a cbc. And so those include AST and ALT that we commonly get in a CMP as well as our platelets that you would get in a cbc. You partner those three analytes in your aids. And these medical organizations and research studies have created this calculation to utilize all four of those different analytes to predict a patient's risk for fibrosis. But you are right that it's really a screening tool. And a lot of these guidelines are recommending a Fib 4 to be ordered on patients that hey are experiencing pre diabetes or type 2 diabetes, have obesity and 2 or greater cardiometabolic risk factors, or have elevated liver enzymes as a need to see if there's additional screening that is needed. Unfortunately, when we look at our own internal data here at Quest Diagnostics, we do a ton of CMPs and CBCs as a main reference lab. But unfortunately, the utilization of the FIB4 test code is still so underutilized when we understand the severity and quantity of patients that could be experiencing fatty liver disease in the United States. And so unfortunately, guideline recommendations take some time to be implemented into that standard care. But what I can say is, even if you're listening, you can go get a fib4 calculator on Google right now yourself. If you go to fib4 calculator on Google, it's important to maybe take a CMP and a CBC that was ordered on the same day, but if you have any of those previous blood results accessible, it's a calculator that you can just use for free online yourself. And so there's some proactive steps you can do in the meantime to be able to do it on your own.
- [07:34]
A
So those are some great points. I wanted to pause here and define rule out tests when we're talking about using the FIB4 score as a first step in liver disease assessment, we essentially mean that it helps identify people who are unlikely to have advanced fibrosis, so they don't need more invasive or expensive follow up testing. So let's walk through this step by step. Let's first start with the patients who get a fib four score that is considered low, and in that case that's a fib 4 of less than 1.3 in those individuals. What should providers be doing?
- [08:07]
B
So in those patients that are lower than 1.3, the guidelines are currently recommending that that patient still gets managed by a primary care team. And really it's a focus on managing any of those obesity or cardiometabolic comorbidities that could be long term driving the risk of fatty liver disease.
- [08:25]
A
Great. So since the Fib 4 is a rule out test and we can do a great job at identifying who doesn't have risk for progression, if a patient receives a fib 4 score that is higher than 1.3, so that would be an indeterminate or high risk range, this means that that patient could be at risk for advanced liver fibrosis and that's a signal to move them to the next step. And the guidelines specifically state that in these individuals they need a liver stiffness measurement by elastography or an ELF blood test. And our offering is the ELF blood test. So can you talk a little bit about the utility of the ELF score, how it works and when providers should be utilizing it?
- [09:04]
B
Yeah. So currently the guidelines are recommending additional follow up testing to confirm the risk of advanced fibrosis or even in cases diagnose those patients of advanced fibrosis. So in a case of indeterminate and or high risk, they're recommending patients to get additional testing through what's known as a liver stiffness measurement and elastography and, and, or the enhanced liver fibrosis score. And both of these are being driven first. Historically it was really popular to get a liver biopsy, but the accessibility and cost we see of that being a single approach, it just minimized access to patients in rural communities as well as it was a huge cost spend for the health care system. And I think we're all at a place where we know the United states spends over $4 trillion on healthcare as a country annually. And so there's a need to find really better and cost effective ways to help diagnose and predict diseases earlier. And so that's why there's been a really big push on a need for non invasive testing options. And the ELF score specifically is the Only FDA indicated serum test being viewed as a prognostic marker for MASTOLD and mash. It's really simply a proteomic marker, which means it's just a test that looks at simple proteins to be able to predict the risk of advanced fibrosis. What we're finding now from a research perspective is about 20 to 25% of a patient population that got a fib 4 would need additional testing like the ELF blood score. So if you think about, again, the quantity of CMPs that are being done annually in the country that could be done on that high risk population of diabetic obesity or, or other cardiometabolic comorbidities, that's 1 in 4 of those patients needing additional testing to see if they have advanced risk of fibrosis. So there's a huge patient population that would benefit from having increased accessibility to this specific test.
- [11:06]
A
Yeah, good point. That's a huge number actually. Right. If we think about 1/3 of patients being at risk for Masold, 25% of those patients that are screened for Fib4 then are recommended to go on to secondary testing. And keep in mind that early fibrosis detection can help guide treatment and prevent irreversible liver damage. So a huge proportion of the population that will benefit from getting this testing. So we've talked a little bit about the idea that if a patient has risk markers that put them into the equation for fib 4, into the follow up test for elf, there are likely patients that have higher risk for cardiometabolic conditions. And we've also talked a little bit about the idea that mass hold is an underlying red flag for cardiometabolic disease. So let's say a patient gets fed into the algorithm, maybe they go on to get that ELF test and then they receive a low risk ELF test back. What should providers be thinking about outside liver disease to help them better understand their patients underlying cardiometabolic risk?
- [12:09]
B
Yeah, metabolic dysfunction associated steatotic liver disease may start quietly in the liver. You know, I want to drive it back to why they made that name change and highlight the importance of looking at what's driving that metabolic dysfunction. Is it insulin resistance in a diet full of sugar? Is it cardiovascular risk? And maybe they have untreated APOB and LP and you can even see more significant risk. When we talk about inflammatory markers, um, we're even unfortunately seeing that it could be kidney disease causing some of that inflammatory metabolic dysfunction risk. As I mentioned, we look at the liver and it plays such a role in our nutrient and hormone Metabolism, but it's also the main organ in charge of detoxification. And if we look at our lifestyle as a whole, some that we maybe make in our own decisions with alcohol and poor diets, but then we also look at things out of our control and the rise of environmental toxins that could be absorbed into our bloodstream and wreaking havoc on our liver. There's so many different factors, unfortunately, that can be causing this metabolic dysfunction that ultimately can cause a rise of liver enzymes that ultimately could be picked up by Fib4. And so even in those patients that maybe are indeterminate or high risk of Fib4, that don't test positive or high risk for Elf, there's obviously a gap there where some sort of metabolic dysfunction is, is putting that patient population at risk for more advanced fibrosis. So it's looking upstream of what could be driving some of that metabolic dysfunction.
- [13:41]
A
Absolutely. Well said. And like you mentioned, patients with MAST do have a two to three times higher risk of cardiovascular events and a twofold increased risk for ckd. And of course, mastle goes well beyond the liver. The shared pathophysiological mechanisms include insulin resistance, chronic inflammation, oxidative stress, endothelial dysfunction, and atherogenic dyslipidemia, which collectively contribute to both hepatic fibrogenesis and vascular injury. And biomarkers to assess risk in these areas often have been labeled as wellness markers. Can you speak a little bit about some of the wellness biomarkers that might help identify risk even before chronic disease develops?
- [14:23]
B
Yeah, you know, I don't think it has to be as complicated, as expensive, as I think the wellness reputation is, because I think there is cost prohibitive factors for a lot of patients to get access into the wellness community. And there's all these kind of fancy tests. And I think what we're, we're trying to drive, it's not always what you're testing for, but it's how and when. And in reality, when we look at a lot of these diseases, there's simple tests like a lipid or APOB that I mentioned earlier, hscrp, looking at an insulin resistance panel with scoring just understanding insulin outside of hemoglobin A1C, you know, there's a, I think a blend of eight to 10 tests that can look at your cardiometabolic risk factors. Because I think there is one thing all diseases have in common. It's the earlier you catch it, the better you have a chance to do something about it. And so I think a lot of times we wait too long. We wait till the heart attack. We wait till we present with steatotic liver disease. And really what we're trying to drive in wellness is how do we have these conversations of ordering some of these simple biomarkers just earlier, you know, and. And I think we're even talking in your mid-20s to upper-30s, because it's really the lifestyle you live in your 20s and 30s that can create some of these diseases in the 40s. And so the earlier we look, the better we have a chance to treat some of these key cardiometabolic diseases.
- [15:46]
A
Absolutely. Well put. I completely agree with you here that wellness doesn't necessarily have to mean complicating testing. It just means proactively identifying risk before it becomes disease. Well, Andy, thank you so much for joining me.
- [16:01]
B
Absolutely. Ton of fun. And I guess we'll close with here's to taking better care of our liver.
- [16:10]
A
That's a wrap on this episode of Healthier World with Quest Diagnostics. Please follow us on your favorite podcast app and be sure to check out Quest Diagnostics Clinical Education center for more resources, including educational webinars and research publications. Thank you for joining us today as we work to create a healthier world one life at a time.