Dr. Mike Smith (Host): This is Pediatric Insights, advances and innovations with Children's Health, where we explore the latest in pediatric care and research. I'm Dr. Mike. And with me is Dr. Sara Hassan from Children's Health. Today, we'll discuss the rise of pediatric metabolic dysfunction-associated steatotic liver disease and explore its current challenges and solutions.

Dr. Hassan, welcome to the podcast. Let's start off real simple here. What exactly are we talking about? What is this kind of liver disease, and why is it on the rise in kids?

Dr. Sara Hassan: Well, thank you so much for having me and thank you for letting me talk about a topic that's very dear and near to my heart. What is going on is that we're having a lot of symptoms and findings of metabolic dysfunction. This is where the metabolism isn't really working well, and it ends up hoarding or storing extra fat inside of the liver.

We used to call this disease fatty liver or to be more precise or maybe more difficult to ascertain, non-alcoholic fatty liver disease, which is somewhat absurd with our patient population to define something by the absence of alcohol. But what it truly is, is that the nomenclature changed and it changed it to something that's a little bit more accurate. And it's linked to metabolic dysfunction that is associated with steatosis or the abnormal presence of fat inside of the liver causing disease.

And so, the easy term right now that we say is MASLD, and we reserve the term MASH or steatohepatitis to those folks who have elevated liver enzymes on top of the finding of abnormal fat inside of their liver.

Host: This abnormal fat that's building up in the kid's liver, why is that happening in the first place? Is it medication-related? Is it lifestyle? What's going on? And why now? Like, why today are we seeing the rise?

Dr. Sara Hassan: It is essentially mirroring the rise of obesity, and it's paralleling that significant sharp increase in kids and teenagers, young adults who are having a lot of changes to their lifestyles. We are definitely pivoting to a fast food culture. We have been in this culture for a really long time. But even if you look at, like, certain recesses in schools, the kids are supposed to go in, eat really quickly, and then leave to go play. We're not really eating well, we're not really eating right. And I think that's causing a lot of issues. it's leading our metabolism to be a little bit slow. It's leading to chronic conditions like obesity, insulin resistance, prediabetes. And most often, what ends up happening is that it leads to this abnormal accumulation of fat inside of the liver, which ultimately can lead to a lot of diseases later on.

 It's alarming because it's starting to happen earlier and earlier. I'm seeing kids younger and younger who have this condition inside of their liver, and it really worries me for their future. Because what does it mean if you have 20 years of abnormal fat accumulating in your liver? And we are pediatricians at heart. We want to make sure that the kids that we see have the best future, and that they're healthy and that they achieve everything that they put their minds to. And it really burdens me to think about what's going to happen to their liver in 20 years or in even 30 years when they're 35 or 37. You know, maybe they're becoming first time parents or they have two kids. And now, they're dealing with sequela of long-term chronic liver disease. And that can include fibrosis, cirrhosis, certain types of cancer. We're talking the need for a liver transplant. So, it could start with a little bit of fat. But if we really don't address it, and this is where it falls on us as pediatricians, if we really don't look at this and fix it, we're setting that child for a not-healthy adulthood.

Host: Yeah. And I think we've learned that through so many adults having this as well, right, what the sequelae are of this disease. It's not benign by any means when we look at the pediatric population, right, and we know it's rising in that population, what are we talking about though? Are we talking about less than 5% of kids, 10% of kids? Can you give us a little bit of a number?

Dr. Sara Hassan: I can tell you 10% of youth in the US have this disease, 10%. And for children who have obesity or whose BMI is more than 95 percentile, those kids are even higher risk. We're talking up to 40, sometimes anywhere between 30-50% who may have this hepatic manifestation, this disease inside of their liver. And it's starting younger. This is what really alarms me. We used to think of this as maybe 15, 16 years old, you know, like adolescents, but we're starting to see this earlier and earlier. NASPGHAN and the American Academy of Pediatrics and then North American Pediatric Society for gastroenterology, hepatology and nutrition are recommending checking liver enzymes anywhere between nine to 11 years old if risk factors are present. So, it tells you, it's creeping in. The clock is somehow moving backwards and our kids need us.

Host: You know, I was in medical school in the early 1990s, and Dr. Hassan, we were not talking about this in a pediatric population, and now we are. That's very worrisome. What are some of the common misconceptions you hear?

Dr. Sara Hassan: That the kids will outgrow this. They're going to hit puberty and it's going to go away, or kids are resilient and it's going to disappear with time. And unfortunately, what we see day in, day out is actually it worsens and it accumulates. And instead of having a disease when you're 20, 30, even 40, now you're having a disease when you're 10.

And it really worries me for what that means for later on. I've had the privilege of sitting on selection conferences, on transplant selection conferences for both pediatrics and adults as a transplant hepatologist, and a lot of the candidates that were being presented were younger and younger and younger, that was incredibly alarming to me. It just makes me feel really worried about what's happening.

Host: In the primary care setting, should we be doing something different here when it comes to screening for this type of liver disease? Is there something we could be doing that we're not?

Dr. Sara Hassan: I think the primary care physicians are doing a fantastic job being the home for the entire family. I know that the recommendations are to really screen, really talk to the family about healthy habits, specific dietary interventions, you know, being outside a lot more. the screening is there, but I think the other issue is access. How do we get these people seen and how do we get it really addressed and how can we nip this in the bud rather than letting it accumulate and grow and sit on it, essentially?

Host: So, I want to talk a little bit, we started to touch on this, and the comorbidities that are associated with this. And, you know, we're specifically talking about, maybe 10 years down the line, 20, 30 years down the line, but what are some of those comorbidities that concern you the most?

Dr. Sara Hassan: I think about MASLD as metabolic dysfunction. So, anything that hits the metabolism and thinking about specifically metabolic syndrome, right? And so, insulin resistance, diabetes, lipid abnormalities, high triglycerides, high cholesterol, low HDL, high LDL, high blood pressure, sleep apnea, we're seeing a lot more sleep apnea.

And in certain teenage girls, I really look for PCOS or polycystic ovary syndrome, and it's becoming more prevalent that we are screening for all of these comorbidities. When those are present, the risk goes up significantly, especially for fibrosis. I'm terrified when I see a kid who has type two diabetes right now, and he's done, because I know his liver disease is going to skyrocket from there. Those kids really need closer monitoring.

Host: It worries me too, because in adulthood, diabetes, insulin issues, you know, we always think of these as a pathology of acceleration, you know, heart disease accelerates, cognition issues accelerates, and all that kind of stuff. And we're talking about this kind of thing in preteens.

Dr. Sara Hassan: In preteens, exactly. In preteens and in early adolescence, and in early teenagers, and in less than 18 years old, those 15 to 18 years old kids. And to be honest, we don't really know what the state of inflammation is really doing to their brains, to their development, to their heart, to their arteries, to their vessels, to their eye vessels, to their kidneys.

But what we can tell you is that from what we can see from population data and just seeing those patients, you know, in and out is that it continues. These accelerating factors continue, fibrosis even develops in these kids, which we used to think that that was not really possible, right?

And now, we know that there are a lot of kids who have fibrosis on their liver biopsy, fibrosis of the liver, righ? So, it's definitely been more prevalent and more there. And thinking about those comorbidities is what's telling us, "Okay, this kid is at a high risk of developing fibrosis. This kid is at a higher risk of developing cirrhosis in the next 10 years, and maybe we should be screening him a little bit differently."

Host: And developing these things when they should be at a time in life when they're in college and they have all kinds of energy and they're starting families, and yet they're going to be dealing with diseases of age. That's very alarming to me to hear that, you know?

Dr. Sara Hassan: It is, and that's why we really need all hands-on-deck for this. Everybody needs to really talk about this and address it, and think about it as truly what it is. The metabolism, when it's problematic, it becomes a disease. It's a chronic disease. And if we don't fix it, then it's going to be an issue.

One of the biggest things that I face in clinic is that people think it's a failure of willpower. And it's not. And that's one thing that I really stress on my family, is that I think about the metabolism as this from zero to 180. You have folks who eat whatever their heart desires and their metabolism is incredibly quick, and you can tell, right? It's hard for them to put on weight, et cetera.

Most people live in that beautiful world where their metabolism is balanced, and you eat right, and you exercise, and you don't have any of these other issues, and maybe you indulge and you eat a little bit more, and then you're like, "Oh, let me just go work out," and your metabolism responds to you nicely.

But there is a good category of folks whose metabolism is just really not working well, and not working for them well and causing them disease. They try their best, they're exercising, they're eating right, they're doing everything that they're supposed to. And it's not just the weight that they can't come down, they can't melt that hepatic fat, they are still hypertensive, even though they're really, really, really trying their best.

And those folks are the folks that we really should be focusing on to help them, because we know that if you're starting to have evidence of metabolic dysfunction at this age, what is going to happen to you later on? And what does it mean for your childhood, and what does it mean for your teenage years?

Host: And it's just not helpful to put it on them even more. They're trying hard, like you said, right? There's a metabolic issue, they're trying their best, they're trying to be active, they're trying to follow those diets, and then to tell them, "Well, you're not doing enough." That's just not helpful.

And a matter of fact, it's harmful, I think, in probably the long run. Well, what do we do? So interventional-wise, what are our strategies? Let's first talk about lifestyle. We touched on some of them. Is there anything specific about lifestyle that we need to get started immediately on these kids?

Dr. Sara Hassan: One of the two things that I think are really helpful, and I think the kids are able to understand when we're talking about them in clinic, is how do we hack our own system? How do we help ourselves to feel better? And one of them is to just get moving, just move as much as possible. Sometimes this advice is really hard for a patient who has had—I'm going to give you an example—if they had a brain tumor and that tumor was removed, and now they have a certain type of obesity that we call hypothalamic obesity, which lead to significant weight gain, but it can also lead to liver disease. Those patients, it's really hard for them to say, "Okay, you know what? Let's go run a marathon." No, we're not going to run a marathon. We should really tailor those expectations to the patients that we're seeing and be very specific about that.

So, movement like walking around the block, if it's safe, if they have an adult with them, and if they live in a safe neighborhood, just trying to move around, just parking the car a little bit further when we're going to Target or Walmart or wherever we shop at. Thinking about those little alternatives where we are moving instead of being sedentary is going to be great.

If we are able to exercise, and if we are health enough, and if our heart is healthy enough and we are able to exercise, please, let's be outside as much as possible, outside in the sense of, "Let's join the Y, let's do more activities," if it's possible. And some families, it is physically possible, but parents work two jobs. It's really hard.

Host: It is, and that puts a lot on the child and tuff. I like the way you say it though, Dr. Hassan. the idea of movement, activity. It's a better message than just get out there and do formal exercise.

Dr. Sara Hassan: I think, you know, not everybody has the luxury to do formal exercise. And if you can, absolutely, please do. But if you don't, just move.

Host: I want to move on to pharmaceuticals that we may be using. What's going on there for treatment?

Dr. Sara Hassan: Well, you know, again, we have to be very selective for our patient population. There's a lot of social misrepresentation of who's taking these medications, versus who actually needs to take these medications. So, when we're talking about these patients who have multiple comorbidities, you know, they have high blood pressure, they are 12 years old or 13 years old, they have liver disease, they have an elevated BMI, they may or may not have sleep apnea, they have all of these things going on. These are the candidates that we think, "Okay, yes, you are a candidate for these medications."

And it all goes back to metabolism. We think there is a problem with a certain molecule or a certain hormone that we call GLP-1 or glucagon-like peptide 1. And we are not really sure yet if the body is resistant to it or not making it well enough or if we degrade it too fast, but something happens with people whose metabolism is really low and not working well and hoarding all of this fat inside of their liver, and it's causing them to have a lot more food noise, to have a lot more things going on.

And those are the patients who will be very good candidate for certain pharmaceuticals like GLP-1s that they're hearing about. And those ones are FDA-approved 12 and above for obesity or metabolic dysfunction. They are approved 18 and above, specifically for the liver condition that we treat in our clinic for MASLD and MASH or steatohepatitis.

Host: With the GLP-1s, what's the outcomes? Are you seeing some good results from this?

Dr. Sara Hassan: I will tell you that two weeks ago, I had a, child that I've been taking care of. Well, he's more like a young adult. And none of my patients, which is really an anecdotal thing, but none of my patients come back and say, "Oh my God, I lost weight." They say, "Oh my God, I participated in a school play." And the mom is crying because she's like, "I have my kid back." "Oh my god, I starred in this and my voice is back and I can focus better because I'm not hungry all the time." One of the kids told me that he didn't realize this until the food noise stopped, but he would eat breakfast and immediately think, "Okay, I'm going to eat breakfast now. And then, in two hours, I'm a take a snack. And then two hours later, I'm going to eat this." And he was so stunned to say, "So, like, people live like this without having to think about whether they're going to eat in two hours?" I'm like, "Oh my gosh, that is a really good observation."

Host: ... and, you know, there's some people with that food noise. I'm glad you're bringing this up because I think it's one of the big things that the GLP-1 agonists help with is reducing that noise. But a lot of people with food noise, you know, they have favorite foods and they get excited for those foods. And if they can't have them, they get depressed, they get anxious about it. That ruins their day.

Dr. Sara Hassan: It does ruin their day. But there are a lot of behaviors behind that. There's a lot of binging behaviors that we see. And it's not a one-size-fit-all, right? So, we are just talking about GLP-1s, but there are so many other anti-obesity medications that are available that we can think about. And I'm so glad that you bring up this point, because we really have to think about who will benefit best from which intervention. Not everybody is the same. And it's incredible to me to see those kids who are no longer hypertensive, who their liver a labs went from 300, 200. Mind you, normal is 22 to 26, all the way down to, like, 60. So, we're almost there, right?

And we're seeing these benefits. And I can tell you when I scan their livers, and previously they had elevation and some findings of fibrosis, and now it's going away, it brings me joy because I see that the liver is regenerating. And that's one of the beautiful things about the liver is that it can regenerate.

Host: Let me ask you, Dr. Hassan, about specifically, you're the expert in the field, you're the specialist, when should a pediatrician, general pediatrician, refer patients to you in the SHINE Clinic, because you have many people you're working with, it's multidisciplinary care, when should they refer to you?

Dr. Sara Hassan: I think if the patient has any findings of liver disease, including just random evidence of fat inside of the liver, or elevated liver enzymes, and they have obesity, it's worthwhile to send to SHINE Clinic. And what SHINE stands for is Steatohepatitis—so fat inside of the liver causing inflammation—Intervention, Nutrition, and Exercise. So, we work in a multidisciplinary fashion to really look at the whole patient, to figure out what's going on. We do focus a lot on the liver, of course, to make sure that, there's no progression of the fibrosis, to stage the fibrosis, to see if there's anything else, because we have diagnosed a lot of folks with not just MASLD and MASH, the fat was just a symptom of something a litle bit bigger, and were able to get them therapies immediately.

But also, we take this chance to really look at the whole patient, "Hey, what's your blood pressure? What's your triglyceride? How can we help there? What are the things that we will be able to do so that we can reduce this?" And then, we have this wonderful dietician, Emily Kelley, who works with me. And then, together, we really tackle what are the things that we can improve in the diet? What are the things that we can prove in exercise? What are the things that we can do? And so, it's multidisciplinary. And so, any patient who has elevation in their liver labs, and they have obesity or elevated BMI, I think they are a candidate for SHINE.

Host: That's probably when they need to see the expert like you. This has been fantastic information. In summary, is there any last word you have for the listening audience?

Dr. Sara Hassan: I would say, we are in a great new era. We finally understand that the metabolism is not a failure of willpower, it is actually a chronic disease. And we are finally in an era where we can actually have therapies. If caught early enough, exercise and nutrition and lifestyle changes can be enough, not in all kids, but in most kids, they can be enough. And so, let's really, really push to take care of all of our kids and give them the best life ahead.

Host: Fantastic information. Thank you so much for coming on the show today. For more information, you can go to childrens.com/liver. If you enjoyed this podcast, please share it and check out the entire podcast library for topics of interest to you. This is Pediatric Insights: Advances and Innovations with Children's Health. I'm Dr. Mike. Thanks for listening.