Chapters Transcript Metabolic Dysfunction Associated Steatotic Liver Disease: What You Need to Know Sarah Henkel, MD, defines metabolic dysfunction associated steatotic liver disease and presents on how to diagnose it in children. All right, we'll go ahead and get started. Welcome to Early bird rounds and thank you all for joining us this morning. Today, we have Doctor Sarah Hinkle and she specialized in pediatric um GI and today she'll be speaking on metabolic dysfunction associated with liver disease and what you need to know. Uh, will you please ask that your cameras, uh, stay turned off and that you are muted during the session. There will be time at the end for questions and you're welcome to unmute at that time, or you're welcome to type your questions in the chat, and Doctor Hinkle will see them at the end. Um, I will also put the QR code up at the end for everyone to scan for credit, and with that said, we'll uh give our attention to Doctor Hinkle. Thank you very much and thank you for having me. Um, good morning, everybody. My name is Sarah Hinkle. I am, uh, one of the pediatric hepatologists here at Washington Saint Louis Children's. Um, and I'm very excited this morning to talk about, um, one of my favorite topics, which is metabolic dysfunction associated steatic liver disease or massled, um, what you need to know. Masled, um, Just so that everybody starts on the same page is the uh new nomenclature for naffold or non-alcoholic fatty liver disease that was changed by the um ASLD um last year, um, and we will get into that just a little bit today. I do not have any financial disclosures. I hope by the end of our discussion today, you're able to define metabolic dysfunction associated static liver disease, learn how to diagnose it in children, and be able to identify two contributing factors to massel, and start to plan the initial treatment of massel in children. First, I think it's helpful to discuss why massled is important. It is so prevalent that I think um sometimes it's um become so commonplace that we, we don't fully take it um as seriously as it perhaps should be. So massel is the most prevalent liver disease worldwide. It is the number one cause of chronic liver disease. It's prevalence ranges you can see um on this world map of adult data from about 13% in Africa um to 25% to almost. A third of adult patients in some populations in parts of the world. Actually, the new data in the US um puts the overall prevalence of massled um or of steatonic liver disease rather, which is a whole spectrum of diseases, um, at 37.8%. Um, in 2017 to 2020, um, and Haynes data, um, and the majority of that 32.4% overall is massled, so that is, um, A very significant number of adults with steatonic liver disease. But in children, of course, the population that we care for, um, the prevalence of masal is still quite, quite significant. It's about 10% worldwide, depending on the criteria that you're using, um, to evaluate for massels, um, and that prevalence is rising. Um I think it's important to note that the prevalence of massel is rising precipitously um in the last 3 decades, and this is actually faster than the rise of obesity alone, which is, um, Remained a little bit more static. So I think um that raises the question that Massel is not directly related to obesity, and not, is not a direct consequence of obesity, but that there are additional modifying factors that it's important that we're aware of. And I think You probably know from your own practice that not all children with obesity develop massels, and there's a range of um BMI children's um BMIs that do develop massels, and so it's not, it's certainly not a direct correlation. I think that's important to notice. Massel is associated with many other diseases within the metabolic spectrum, um, and actually makes these diseases worse. It's a modifying factor for other diseases. It, um, although it's a liver disease, it exists within the context of all, all of these other um diseases and metabolic dysfunction, and is not in fact isolated to the liver. Um, we know that children with massled, um, adolescents in particular, have increased morbidity and mortality compared to age mates without masalt. In adults, um, and this is a figure from an adult paper, but I thought it was a nice illustration. Um, in adults, coronary artery disease is actually the leading cause of death, um, not liver disease or end-stage liver disease or cirrhosis, um, but coronary artery disease, because we know that massels, um, and the metabolic disarrange derangements that take place within the liver make, uh, Uh, coronary artery disease worse worse control of diabetes, more difficult. Um, so if you have diabetes or pre-diabetes and massalt, it is more difficult to control blood sugars, um, than if you did not have mass salt. Um, so that's, I think an important thing to recognize as well. Um, we know from the COVID-19 pandemic that it made, uh, COVID more severe in many patients, uh. And uh there's newer data out that in pediatric mass chronic kidney disease, um, is, is more prevalent and is independently associated with uh increased liver fibrosis, which, um, I think can be something that's quite significant to see in children. And again, masel is not uh isolated steatosis in the liver, um. Without causing any, you know, irritation or other effects in other organs. Um, it can be a progressive disease. So, um, a few histology slides because I, I like a visual, um, illustration that, um, you can start with a normal liver here on your left, on the left side of the screen. Um, it progresses, it can progress to massal, which is steatosis, um, with elevated liver enzymes, but on histology, you don't see evidence of hepatocellular injury, but this can progress to mash, which is steatosis, along with hepatocellular injury, um, on histology. Um, so you may see ballooning of hepatocytes, um, you may see, uh, inflammation. Around the hepatocytes, and you may see the development of fibrosis as well. And then this can also progress in some patients, and again, there are modifying factors here, not all of which we have identified. Um, that can progress to mash cirrhosis, and that is actually, again the number one reason that adults are added to the liver transplant list in the United States is mash cirrhosis. Um, of course, in the setting of cirrhosis, you are, um, at risk of developing hepatocellular carcinoma, particularly over time. Um And sometimes in adults, in particular, um, and in older children, since this disease is often asymptomatic, they may be at a very advanced stage of disease when it um is even initially diagnosed, and it's hard to, um, To kind of walk back from there. So, um, important to be aware of the prevalence of this disease and diagnose it early, um, if possible. So now that we understand why Masel is so important, how do we diagnose it? Um, Masled is Again, the presence of steatosis in the liver without any other cause for um steatosis and with elevated liver enzymes, persistently elevated liver enzymes. So we'll go through this in a little bit more detail. Um, persistently elevated liver enzymes, primarily we're looking at the ALT, um, the ALT, of course, is more liver specific than the AST. Um, generally, um, our NAS began our, uh, our professional society guidelines, um, stipulate that the liver enzymes, the ALT, has to be, um, 2 times the upper limit of normal, twice in a 1 to 6 month period. Where the upper limit of normal, again, this is according to Ehain's data, that's the criteria that we use typically, is 22 in adolescent female patients, and 26 in adolescent male patients. And so, um, although, as I'm sure you have seen, many of our, uh, labs have different, um, Uh, different parameters for the upper limit of normal. Typically, if it's if it's an ALT of above 44, um, twice in a 1 to 6 month period in a female patient, or, um, what is that 52 in a male patient, that um would count as persistently elevated liver enzymes twice in a 1 to 6 month period. Um, often when we see elevated liver enzymes, um, one of the next things that we're going to do is get a liver ultrasound, um, or perhaps they've had an ultrasound or a CT, um, for another reason, perhaps for abdominal pain that, that happens, um, in the reverse order as well. Um, and so the next part of the criteria are supportive imaging findings. So you will often see a liver ultrasound, um, that says there's uh diffusely increased ecogenicity consistent with hepatic steatosis, um, and so that would, that would be supportive imaging findings. The next part of the um criteria that I think are really important are no secondary cause for fat accumulation or liver enzyme elevation. So, massled is a diagnosis of exclusion. We do not at this point have um one simple blood test that if it's positive, that is massled. If it is not, then it's not massled. We have this conglomeration of criteria. And that we have to put all together um in order to diagnose massled, and I think it's really important that we are looking for other diseases and other causes of liver enzyme elevation, because if we don't, we could miss something that's really important and needs to be treated. So, for example, when we are um evaluating for massal, oh sorry. Um, when we're evaluating for masalt, we are, um, you know, observing that the child has persistently elevated liver enzymes, and then we are screening for other liver diseases or ever other causes, um. of liver enzyme elevation, um, or fat accumulation. So one of the things that, um, you know, we always ask when kids come in with liver enzyme elevation is, you know, why, why were the labs done? Were they symptomatic in some way or We, um, were they sick at the time? Was this, you know, screening before starting a medication or had they just started a medication? Were they perhaps on an antibiotic that's known to known to cause drug-induced liver injury, um, at the time that the liver enzymes were checked and so that context in which the liver enzymes were obtained and the ultrasound were obtained. Um, are really important for us, um, to understand the kind of the full context of, uh, where the liver injury might be and might be coming from. The other important um thing to do is screening for other chronic liver diseases, and so when we see a child with elevated liver enzymes, we also Um, that are screening for not only infectious hepatitis, um, like hepatitis B and C because those are your chronic, uh, hepatiss, but also autoimmune liver diseases, including celiac disease can cause hepaticstatosis and elevated liver enzymes, um, autoimmune hepatitis, um, And PSC primary sclerosis cholangitis, we screen for um a couple of genetic diseases in particular, like alpha one antitrypsin deficiency, um, and, uh, Wilson disease, which can also cause um the appearance of steatosis on an ultrasound and on a biopsy, um, and elevated liver enzymes, and these are things you do not want to miss because the um consequences of that can be catastrophic. Um, and so again, I think it's important to, you know, approach elevated liver enzymes within a full context and with curiosity rather than, you know, looking at a BMI, looking at liver enzyme elevation, and making a presumption, but each child that we care for certainly deserves, you know, that full evaluation. We're also evaluating whether these children have at least one cardio metabolic risk factor, um, which we will, um, get to in the next slide. And I did just want to mention, sometimes children, um, end up having a liver biopsy, um, if the diagnosis is unclear or, um, we are evaluating for something else. And so the presence of more than 5% teatosis is excessive steatosis in a liver biopsy, but Um, we do try to avoid those if possible. So the cardio metabolic criteria, and this is actually um new from the uh change in the ASLD nomenclature last year, um, in the kind of overarching steatatic liver disease um umbrella term, um. In distinguishing massled from other causes of steatoic liver disease, the um adult criteria are there on the left, just for comparison and the pediatric criteria, um, on the right, and we'll walk through them quickly. Um, so first, I think most of us, um, are aware of the BMI criteria uh greater than the eighty-fifth percentile. This also um factors in uh the possibility of a, of an elevated waist circumference. Um, I think most of us are not doing waist circumferences routinely in clinic, um, for many reasons, but that is, um, a, a criteria that's available. Um, an elevated fasting serum, glucose or hemoglobin A1C. So, Your prediabetes, um, or development of type 2 diabetes, um, elevated blood pressure, um, greater than the 95th percentile or um greater than 130/80, um, hypertriglyceridemia, or perhaps they're already on a lipid lowering treatment, um, or a low plasma HDL or again on a lipid lowering treatment. So now that we understand why massel is important and how to diagnose it. I think it's helpful to understand why kids get massled in the first place, and it's very much a multifactorial disease. It is the combination of genetic and environmental factors, and again it's part of a spectrum of metabolic diseases, rather than a simple, um, you know, combination of a genetic background or an an unhealthy diet, quote unquote, um, alone. There are many, many physiologic changes that contribute to how the liver processes and utilizes the energy that we consume. Um, I think this figure is a nice demonstration from a nature review a few years ago, um, about characteristics that are common in pediatric and adult muscle both, and I think many of them are quite interesting. Um, they're quite wide ranging and um affect many different body systems, and I think we, we wouldn't automatically think of all of these. And so some of the things that I think we do think of, um, just to walk through the figure briefly, are, you know, the commonalities of overnutrition, particularly high ratio of fructose in the diet, um, a lack of physical activity. Macronutrient deficiencies, um, particularly vitamin D, and but other fat soluble vitamins as well are particularly common in massel. The, uh, children with massalt actually process vitamin D a little bit differently and not as efficiently. So vitamin D deficiency is incredibly common in in all of us, but, uh, in particular in masalt. Um, we've already touched briefly on Uh, the presence of, uh, hypertension, um, kind of coincidence with mascle, um, vascular injury. And again, there, um, I think one that we don't always see and don't always appreciate is, um, increased carotid intimate media sickness. And again, this has been found even in adolescence, um, compared to children with similar BMIs and without massal. Um, we, of course, have been discussing the, uh, hepatic statosis and portal and lobular inflammation or fibrosis in the liver. Um, but I think again, it's helpful to think of it as a more global disease, um, and as an overall pro-inflammatory state, um, where there's mitochondrial dysfunction, oxidative stress, um. And other physiologic changes in the liver rather than simple teatosis alone. Um, and I think that's an important consideration when you're thinking about how the, how the body overall is working. Um, some other things here on the right side, and we'll dive a little bit um deeper into some of these, um, people who have a Hispanic background are um at a particularly high risk of massled. Um, people who have a visceral adiposity phenotype, um, who have a greater proportion of insulin resistance, dyslipidemia, leptin resistance, um, there have actually been some studies about intestinal dysbiosis and bacterial overgrowth in muscle that it's more prevalent, um, some hormonal changes, and then there are some known, uh, polymorphisms and genetic changes that seem to make, um, Massled more prevalent as well. Um, or put you at a higher risk for massled rather. Um, one other thing, well, many other things I think are interesting. There are risk factors that contribute to massel that, um, take place over the course of an entire lifetime. Um, these are not, uh, things that appear in adolescence alone, but it's really, um, this kind of global milieu of many different risk factors, many of which the child does not have any control over all of, all of us don't have control over, so. Some of these are starting even when the child is in utero, um, with the presence of gestational diabetes, um, carrying a higher risk for massled, an elevated maternal BMI carrying a higher risk for massels, and both high and low birth weight infants are at a higher risk for developing masled um in the future. In childhood, of course, is where you're, we often start to see the first signs of metabolic syndrome, um, including in, you know, hypertension and insulin resistance, um, as we discussed with the cardio metabolic risk factors that are now, um, part of the criteria, um, in adolescence, there's a physiologic um increase in insulin resistance that is transient but can also contribute to the, um, Development of massel, um, because it happens around the same time that that some other dietary changes and um And uh children choosing their own activity levels may happen. This is often when we um may start to see the onset of Nash, um I'm sorry, MASH, particularly on those biopsies. Um, this, again, can sometimes go underdiagnosed or um has it been able to be sufficiently treated for lots of different reasons that we'll also discuss further. Um, but in adulthood, cirrhosis, hepatocellular carcinoma, um, and further, um, manifestations of the metabolic syndrome can develop. So this really is a childhood illness that, you know, starts in childhood, but continues throughout the lifetime and so important to recognize and intervene early if we're able to. Um, another, uh, thing, as I mentioned, uh, a moment ago that contributes to massled is, uh, the phenotype of visceral adiposity, and I wanted to dive into this, um, just a little bit. So, um, visceral adiposity. Um, and central adiposity or something that I think we, um, appreciate on uh exam, but I think don't always, um, or may not always think about how that may be, uh, manifesting within the body. So, there are two different obesity phenotypes, visceral adiposity and subcutaneous adiposity. Visceral adipose tissue is metabolically active, and so those patients um who have a greater proportion of um visceral adipose tissue are going to be at a higher uh risk for developing massels and overall dis metabolism. So this slide, I think, um, is a really interesting. Uh, illustration of how um people with entirely the same measurements can have very different, um, things going on under the surface. So these are, um, transverse uh images from a CT, um, you can see that the, these are in adult patients with the same um the same data holds in children. Um, you can see that in the top figure, these two patients have the same body fat percentage or the same age, sex, and have the same BMI of 24. And yet the um Patient on the. Right has um much more visceral fat, much more um subcutaneous fat in this particular cross section, um, and again their measurements are the same. So I think this also starts to tell the story um that Weight and BMI and uh And all of our, you know, other measurements exist all in the context of each other and are each single data points rather than, you know, the entire story. Um, on the bottom figure, these or the bottom, uh, CT cuts in this figure, these two patients have the same body fat percentage, or the same age, sex, and have the same waist circumference. And again, you can see that um the patient on the right seems to have a greater proportion of um subcutaneous fat and a visceral fats, um, and the patient on the left does not display in the same waist circumference, um. And so we do not always know what's going on, you know, just from, um, what's going on metabolically for a patient, just from, you know, measurements alone or a couple of data points alone. But really, this is a whole um spectrum of disease that's important to, um, be thoughtful about and put into context. Uh, one, additional modifying factor that has had a lot of research into it that I think is interesting to think about, um, and be aware of is perhaps the most well studied polymorphism, um, in massel, that's, um, a polymorphism in a gene called PNPLA 3, which codes for um a protein that is important in lipid metabolism called adipoutrin. Um, this PNPLA 3, variant, you can see I'll, um, step through this chart a little bit is the um light colored piece of the pie. Um, and it's so is the minor allele, um, in this map of the world, and you can see it, it appears to be the minor allele in most places, but the proportion is very different, um, and in particular the places that the minor allele, um, actually becomes the major allele in uh Mexico and um is about half and half in the Hispanic American population, but you can see is more prevalent even in Um, some places in Asia. Um, Uh, is important because these are the um ethnic groups where we do see a higher proportion of massled. We know that they're at higher risk um for developing massels unfortunately. Um, we know that that um particular polymorphism, um, results, it results in a miss sense mutation, and it has been associated with um many different Um, things that seem to worsen metabolic derangements, including, um, a higher proportion of adiposity, a greater risk of, um, developing fibrosis, um, because it has this kind of synergistic effect with adiposity. Um, and then additionally, which I think clouds this picture, many of the places where this, where the PMPLA 3 polymorphism is more prevalent, um, overlap with places in the world where rice makes up a large proportion of the diet, um, rice because of the way that it's grown, um. And processed, um. Holds a lot of arsenic and um therefore increases the consumption of arsenic in um many parts of the world, and arsenic is also um has also been found to increase the risk for developing massals. And so there's all of these things, again, that compound and like little risk factors that put together, many of which we don't have control over that increase the risk for massalt. So now that we can understand why it's important, what it is, and kind of where it exists in the context of other metabolic diseases. I hope that we are feeling motivated to start to treat masel and so how do we start to treat it? This also unfortunately is not as straightforward as we might hope. Um, the mainstay of treatment for massel, as I think, and many of us know, is dietary and lifestyle counseling. However, um, this ranges widely across, you know, providers that are giving these recommendations. So, um, this data I think is really interesting. Uh, there was a survey done. A few years ago, um, among gastroenterologists, um, in the United States and Canada, and, um, To understand what recommendations specifically they are um giving to patients with massels. And I think um my takeaway from this, and we'll walk through it a little bit, is that the guidelines that we're giving and the recommendations that we're giving. are relatively heterogeneous. They're not always clear, not always measurable, and frankly, not always root rooted in data. Some of them are, you know, seem to be quite biased, um, and so here, um, some of the things that were recommended. Are, you know, most people, about 75% of um gastroenterologists, um, made a recommendation regarding sugar intake. Most of those were about avoiding sugar-sweetened beverages, um. But almost half of gastroenterologists also felt comfortable making recommendations regarding um macronutrients overall, decreasing carbohydrate intake, decreasing fat intake, um, even increasing protein intake. And, um, about the same proportion, a little bit more, um, a gastroenterologist made overall eating style recommendations. So regarding eating out, clean eating, which is my favorite, um, setting a specific calorie goal, um, paying attention to a smaller portion size, um, eating things with a low glycaemic index, um, a few recommendations were also made about increasing fruits and veggies, increasing water, um, increasing fiber. And um a small proportion, only 2%, um said that they made individualized recommendations for each patient. And I think, again, from the, you know, this relatively long list, I think we can appreciate that even discussing a few of these in a brief visit with the family who, you know, may be overwhelmed by, you know, coming to the city, coming to the doctor, um, in general, and who may not be familiar with a lot of these concepts, may be overwhelming and may not lead to success. I think it's um important to think of all of our recommendations, um. For massled as not only existing within the the individual, because these, you know, are pediatric patients, and we may not see all of these, um, all of these bubbles. Um, this is a figure from the same paper that are also contributing to this patient's success. We may only see the Barriers to treatment, um, the results of the barriers to treatment rather than the success of the treatment, and we may not be aware of a lot of these things. And so just to kind of highlight some of the barriers that um are available, many, many families see this as a personal problem of the patient because that's, you know, who we're focusing on. At the visit that it, it is somehow, you know, a 9 year old or a 12 year old's, um, specific food choices or specific, you know, inactivity choices that they need to manage and they need to control by themselves rather than something um that would be beneficial for the whole family to modify, you know, they, um, May not want to make changes as a family, particularly, you know, older members of the family, um, may not have that insight to understand the kind of the things that are good for the liver and the things that are good for massled treatment, um, are often good for all of us, including, um, getting enough sleep, um, not being on the screen all the time, um, you know, eating more fruits and veggies and some of the other um things that we discussed routinely. Um, routinely and repeatedly to kind of reinforce those ideas and discuss why they're important. Um Sometimes, uh, you know, patients often don't have access to an intensive, um, obesity management program like we have at Saint Louis Children's in our Healthy Start clinic. Um, it may be very time consuming, um, and very difficult for them to get there, um, you know, which is why we try to do virtual visits as well, um, and incorporate some virtual visits as well, um. Even if, you know, children themselves feel motivated, again, they may not feel that support from their family, they may not, you know, feel that support from their friends, the families. May still have a language barrier even if we use an interpreter and not understand, um, you know, fully what we're describing. They may have, you know, a lack of nutrition knowledge. So if we fail to give them the tools and fail to give them, you know, really specific recommendations, um, that are tailored to them and limited in scope. We may then see a, you know, a failure of treatment where in fact they, they don't have the tools to employ those treatments. And I think, again, while we're treating pediatric patients in in lots of diseases, um, but important here in this context that social determinants of health have a major impact on our family's ability to follow these recommendations. So many of the families that we treat um live in food deserts, have limited food budgets, um, and don't have the time or feasibility to prepare, you know, healthy, fresh meals, um, or Many of the things that we're recommending, often, you know, families, um, particularly if there's a one parent household, are, you know, going between caregivers, or, you know, working after school and the kids are kind of on their own. They, and so the kids are then left to, you know, figure out their own food, what they're going to eat for snack, what they're gonna eat for dinner. Um, Employ their own, you know, activities and, and increased activity levels and exercise regimens that we've discussed. Um, they may have not have a safe place to play, um, or if they're, you know, in an apartment or it's cold outside, they may not, um, feel like they can, you know, jump around and get, get their heart rate up to be active. Um, there's some newer data that, um, That finds that air pollution is associated with increased liver fat and stiffness um in Latino youth, and um that PMPLA 3 polymorphism that we were talking about um a few moments ago, um, also has a synergistic effect um or a more pronounced effect um with the air pollution. And so these are again all things that are out of our um control, um. And that we You know, try to overcome in some ways, but I think it's important to understandASL within all of these contexts, um, so that we approach it kind of as a team, and how are we going to overcome these things, um, rather than, uh, rather than looking only at the patient alone. Uh, one thing that we do focus on, um, because this is rooted in data and is a very specific intervention, is limiting free sugars in the diet. So, um, this is a paper from, um, a few years ago, um, in 2019, where they took um 40 adolescent boys and randomized 20 to a usual diet, and 20 to a low uh free sugar diet of less than 3%. And so what that means is, um, this dietary intervention was, was quite intensive. They had steady staff, um, go to the homes of the 20 folks who were randomized to the low sugar diet, um, throw out things that were, um, higher in free sugars, including like You know, processed snacks and condiments like honey and ketchup. Um, the study staff went grocery shopping with the family so that they could, you know, check labels together and improve, you know, health literacy, um, in that way. Um, so certainly not feasible on a broader scale, um, but this is kind of how intense this intervention was to Demonstrate actually a really considerable effect in a short amount of time. So what they found was there was a 7, about a 7.5% decrease in satosis, hepatic statosis, in only 8 weeks in this low sugar diet, um, intervention with no other changes. Um, and in the patients who followed the usual diet, um, there was a less than 1% decrease, so it was significant. They also found um They also found uh decreases in uh secondary outcomes. So I'll explain this chart a little bit because I think it's um really neat, but we may not be used to looking at these. Um, so each um line on here represents a patient, um, randomized in the trial. Um, the patients in light blue, like this light blue gray color. Are, are the ones randomized to the free sugar diet, um, and the ones in this yellow orange color are those on the usual diet. Um, so the, the outcomes that we're looking at here are um the MRI fat fraction in the uh top left figure. Um, the ALT next to it here, the AST in the bottom left of the figure, and then the GGT, um, in the bottom right of the figure. So the top line is the starting point, and then again, each individual is um one line and the dot is the ending point. So in the MRI. um, fat fraction, you can see almost every patient, um, in the low free sugar group, um, decrease their MRI fat fraction. Similarly, in the ALT measurement, the AST measurement, and the GDT measurement, some of them quite considerably. Um, and in the usual diet group, um, in the MRI fat fraction, you can see, um, many of them did decrease their fat fraction. Um, but to a lesser degree, um, and kind of the same story in the laboratory parameters with the ALT, the AST, um, and the GGT. So I think it's nice to see the individual data points there. Um, and so this study nicely illustrates that if nothing else, um, decrease the decreasing the amount of free sugars in the diet, of which the largest source in most of our diets is um sugar sweetened beverages, that that can um have a big effect on hepatic statatosis and laboratory parameters overall. We do so um. Uh, make some kind of non-nutrition guidance, um, in our healthy start clinic. Um, I think, you know, my personal practice is to, um, kind of open up our first clinic visit discussing, um, metabolic health in general rather than weight alone as weight is, you know, only one data point, and you can still improve, you know, your fat fraction and laboratory parameters, um, without significant weight changes. Some of that is, um, With encouraging strength, um, and cardiovascular exercise as well, you know, there may be some, um, change in muscle mass that doesn't um lend itself to as much weight loss as you might otherwise expect because we are not, you know, only focusing on adipose tissue. Um, we discussed limiting screen time. And we really do like to set specific limited goals, so those um smart goals that are specific, measurable, um, attainable, so that kind of goes in the context of all of the social determinants of health that we were talking about before, um. And time limited. Um, but we also really encourage family participation and sleep as a lot of your metabolic health is also um improved with um better sleep habits. That is, you know, a larger, a larger lecture than we're discussing today, but all of these things are important and we try to impress that upon our patients um in our Healthy start clinic. Many, uh, families and, and I think many folks are, since some of the lifestyle modifications can be, um, can be tedious, and we do not always see, you know, quick results with these things, you know, are looking at medication options to augment, um, augment our success with uh lifestyle interventions as well. Um, unfortunately, we Classically have had kind of limited medication options, but there's actually a lot of new stuff happening um in the world of um massals, um, and particularly mash, so, um, metabolic dysfunction associated statal hepatitis, um, in the last couple of years. So, Um, we do sometimes do vitamin E. Um, this is shown in the tonic trial to improve the ballooning of hepatocyte, so it improves the histology, it supports the cell membrane, um, but it doesn't improve laboratory parameters or, you know, perhaps change the course of disease. So I'll use, I'll, I personally will use it if they're, um, histopathologic changes, but, um, you know, otherwise it Sometimes it's just one more thing for folks to take, but it's a very low risk of an intervention if they want to take something, um. You know, it's classically, we've used um metformin if there's insulin resistance, though this, you know, has some mixed uh data on success. Um, a lot of people, um, including ourselves, are very interested and in and excited about, um, the newer medications for obesity, including, um, GOP1 receptor agonists. Um, there's not tons of data, um, about them in improving, um, Mazzled, but there um was an adult study that came out uh just recently about improving um The adiposity, um, and not progressing to cirrhosis, um, for patients with massel who were on GLC GLP one, receptor agonist. So I think that's potentially very promising, um, in the future. Um, Jenny Sprague of endocrinology had an excellent, excellent, um, early bird rounds on, uh, that involved, you know, discussing GLP1 receptor agonists a few weeks ago. If you wanna Um, learn more about them. That was um super helpful as well as other obesity medications. And then, um, just this year, um, a medication called resmero, or resifra, um was approved for um For MAS for um adults. So we can use it in patients that are greater than 18. Um, so resmidoro is a thyroid hormone receptor, um. Partial agonist in the beta subunit that works by um decreasing lipogenesis, increasing fatty acid oxidation. Um, it was shown to improve sayatal hepatitis and improve or stabilize liver fibrosis. So you can't use it in decompensated cirrhosis, um, but it may stabilize or improve, um, fibrosis, which of course is really exciting as this is, again, Um, the number one reason that adults are added to the liver transplant list in, in the United States currently. Although part of that, as a side note, is because, um, we have new very effective, uh, hepatitis C treatments. And so that's um hepatitis C and hepatos cellar carcinoma due to um cirrhosis associated with hepatitis C out of that, uh, top spot. So all good things. Um, in the future, um, just briefly, there's lots of research into massL again, it's so prevalent, um, there are new therapeutic options, um, that are under investigation, including, you know, some of those, um, GLP1 receptor agonists and, um, hopefully resi and younger age groups will be available um in the future as well. Um. There are some imaging modalities that are, um, helpful, which we're able to use with increasing frequency. Um, if you ever see a fibro scan on one of your patients, that's what this, um, picture on the right is. Um, this is a, uh, one of the portable fibro scan devices, which is an ultrasound, um, technology, which measures the amount of fat and liver stiffness in the liver. So it can be a really helpful, um, Way to measure progress over time again, especially if you're not getting, you know, linear improvement or linear changes in your um laboratory parameters, and because, you know, an ultrasound can demonstrate the presence of what appears to be hepatic satosis but can actually measure changes over time. And so this is a really helpful. Um, imaging modality to use for us, and that, um, we have ongoing studies with. Um, and then again, there's lots of work into genetic markers, um, signaling molecules, um, that might help us understand in the future why, you know, some kids get more severe disease and others do not and say it, you know, relatively mild, um, simple steatosis with some mild liver enzyme elevation. So, in conclusion, Massled is multifactorial. Um, I hope you remember to maintain curiosity to make an accurate diagnosis and evaluate for those other diseases or other causes of liver enzymes, rather than, you know, related to obesity alone. Um, nobody really needs a sugar sweetened beverage with great regularity. Um, when we are setting goals for our patients, it is helpful to take it within the entire context of, you know, their home life and use specific evidence-based goals and keep them really limited. Um, and then we want to be monitoring for comorbid conditions as well, um, including hypertension, dyslipidemia, um, vitamin D deficiency because all of these are really important, um, to kids' long-term health. So, Um, with that, if anybody has any questions, very helpful to discuss. I really appreciate your attention. Um, and if there's anything I can help with in the future, please feel free to email me. Thank you so much for speaking for us this morning. Um, we do have one question in the chat, and then I will also pull up the QR code for everyone. Oh, that's a great question about when we should start screening for mastel. So, um, the AAP recommendations are to um obtain liver enzymes, so including an ALT, um, for children with an elevated BMI, so greater than the 85th percentile, um. At age 11 to 12, although, you know, a lot of folks will end up doing it um earlier if clinically appropriate. Thank you, Doctor Hill, for that question. Um, if anyone else has questions, you're welcome to unmute if you'd rather do that. Looks like we got one more in the chat. Um, any evidence in diet sodas can have similar effects. I'm guessing like similar effects as to like regular sugar sodas. So I think diet sodas are a little bit of a um Complicated question and part of like part of this is my personal opinion from from lots of different reasons. So if a child like really, really, really, you know, needs to drink soda, you know, we, you know, certainly have some kids with some sensory issues too, um, are like that. A diet drink is preferable. Um, I do caution against it sometimes because we and I'm seeing a lot of children who, um, also have, you know, belly pain, um, sometimes they have constipation, diarrhea, and there's some data from, um, a couple of years ago about artificial sweeteners being, um, IBS triggers, irritable bowel, um, syndrome triggers. And so I do, you know, just speak about that when we're, when we're talking, um. And recommend favoring water is kind of the major thing that you drink overall, um. So kind of with that caveat, they're not known to have the same effect, but they also may not be great overall. Um, if liver enzymes are normal at age 11 or 12, how often do you repeat? Um, I would not necessarily repeat them every year. I don't, I don't remember the official recommendations on that. I think, um, Just kind of like as indicated, so you're you're seeing a lot of like weight change from year to year or you would get them for for another reason, um. I think that's fine to repeat liver enzymes, but somebody please correct me if I'm wrong about frequency. Um, so if they have an elevated ALT, this is a great question. If they have an elevated ALT, how often should we be rechecking their level? I think it's a little bit of a complicated answer. So if you check an ALT because, you know, perhaps you have a child with a BMI and then, you know, 95th percentile and their at their 12 year well child check. Um, their ELT is like 55-ish. I would probably recheck it in about a month. If you're checking for like somewhere between a 1 and 6 month period, or is that kind of appropriate time frame, um, or most helpful time frame. Um, if you are, um, checking an ALT and you find that it's like 455, um, please recheck it sooner or give us a call, um, and see how we can help. So it depends a little bit on the degree of elevation, um, that would kind of dictate how, how fast I repeat it. Um, If one of the family members hassled, should we scan the rest of the family? Um, and we do we make the recommendation of the treatment plan to all family members? Um, that's a great question. I think whether you're screening the rest of the family depends on, you know, whether these are pediatric patients and um whether you're their PCP and kind of what's going on with them individually. Probably because this many of the same genetic and environmental factors would that pertain to one patient would also affect um You know, there there are other family members, and I think um You know, what I often say is clinic in clinic, um, as I said this morning is the things that are good for our liver, so, you know, staying active, drinking mostly water, um, staying away from sugar sweetened beverages, um, these things are, are good for all of us, like they're not really like massled specific things that are only good for one specific disease. Like these are good things for all of us to kind of, you know, keep our bodies healthy and strong in the future. So I think it's helpful to get the whole family on board. Lots of great questions. So thank you all for your participation. Um, before we get going, I did want to let you all know of next week's early bird rounds and what we can expect. I'm gonna put that in the chat so you can see it, um, but our, uh, speaker will be from a pediatric adolescent, and adolescent gynecology. We'll put that in here. And then I also wanted to let you all know of our last speaker series for 2024, we'll be having a speaker from psychology about understanding and treating pediatric OCD and that'll be on Tuesday next week, the 19th. But thank you so much, Doctor Hinkle. We really appreciate your time and what an enjoyable, uh, presentation this morning. Thank you, everybody. Have a good weekend. Created by Presenters Sarah Henkel, MD Assistant Professor of Pediatrics Gastroenterology, Hepatology, and Nutrition View full profile
