Hello, welcome to today's webinar. I'm Dr. Shelley Keating and will be the moderator for today's session. On behalf of the ADA Exercise Physiology Interest Group Leadership Team, I'm really excited to welcome our presenters to discuss the latest evidence supporting exercise and lifestyle interventions for Maseldy and MASH from both clinical research and patient perspectives. So here is a glance at today's agenda. We'll provide a few announcements and then we'll introduce our speakers in a few moments. They will each present and will be followed by a Q&A panel discussion. The presenters will be taking questions from the audience at the end of the event, but please don't wait till the end of the session to enter your questions. Instead, go ahead and type into the Q&A box into your control panel. Please just be sure to use the Q&A box and not the chat function for questions. We'll be using the chat box to send you important links during this announcement segment. The ADA Exercise Physiology Interest Group Leadership Team coordinated this webinar. I wanted to take a moment to thank all of the members of the leadership team for their work throughout the year to provide opportunities to the interest group members. Learn more about the ADA's interest groups at the link now posted in the chat. The ADA Exercise Physiology Interest Group also has an upcoming hands-on webinar as part of the Helmsley Hands-on Webinar Series titled Optimizing Pediatric and Adolescent Diabetes Through Exercise. This webinar will be exclusive and free to all ADA members and attendance provides an opportunity for one CE credits. This webinar will be held on Tuesday, December 10th from 3 to 4 p.m. Eastern time. So please register using the link that's now pasted in the chat. Now, are you an ADA member who's within 10 years of completing your professional training? If so, you may be eligible for our Exercise Physiology Interest Group's Early Career Abstract Award. They'll be awarded at the 85th ADA Scientific Session in Chicago. For consideration, please submit your abstract no later than January the 6th. And for more information, please visit the link on your screen and now in the chat. Thank you. Finally, it's my great pleasure to introduce today's first speaker. Dr. Jonathan Stein is an Associate Professor of Medicine and Public Health Service at Penn State, specializing in metabolic dysfunction associated steatotic liver disease and exercise. He's authored over 110 peer-reviewed papers and serves on the editorial boards of major hepatology journals. Dr. Stein is also the Maseldee Consultant for the American College of Sports Medicine's Exercises Medicine Initiative. Dr. Stein is also the Director of the American College of Sports Medicine's Exercises Medicine Initiative and serves as the Fatty Liver Program Director and the Research Director for the Penn State Health Liver Center. Today, Dr. Stein will cover the latest clinical evidence on exercise and lifestyle interventions for managing Maseldee and MASH, as well as key strategies for personalizing implementation and practical challenges in translating research into clinical practice. Thank you very much, Dr. Stein. Dr. Keating, thank you so much for the introduction and always a pleasure to be here. I'm gonna go ahead and share my slides, so everybody just let me know when you see them. And we see the big version? All right, I'm seeing Dr. Keating nodding, excellent. Well, first and foremost, a huge thank you to ADA and the organizing committee, Michael, Liz, Annie for having me today. It's an absolute delight to be here. We're gonna talk a little bit about exercise and metabolic dysfunction associated with steatotopic liver disease or Maseldee. And yes, that is an alphabet soup. And we'll talk a little bit about what this is. Here are my disclosures, including research funding from the NIH. And it's always for us as clinicians about the patient. So I'd like to start off today's presentation and share with you somebody that we saw recently in our large multidisciplinary program. So this particular patient was a 62-year-old grandmother. She had diabetes and then newly diagnosed at-risk MASH or metabolic dysfunction associated steatohepatitis, which is the type of fatty liver disease that's going to progress. Shown here are some of the markers that we would see on a fiber scan, which is an ultrasound-based technology we use to stage the degree of liver fibrosis. And like many of our patients here in Central Pennsylvania, she was sedentary, doing 60 minutes per week of light physical activity. And then she consumed a diet high in processed and ultra-processed food, including many fructose-rich beverages. And when I talked to her more during her interview, she said, hey, I'm really here, doc, because my primary care provider wants me to lose weight, but didn't tell me how much. And then they also asked her to start metformin for her newly diagnosed diabetes. But she said, I don't really want to take medications. And I know diet and exercise are good in general, but how can exercise actually help my liver disease? So, to me, this common scenario we see in the clinic brings up several questions that are important for us to consider. And first and foremost, if we're going to get somebody to buy in and to make healthy lifestyle choices, they have to care they have a problem in the first place. So, secondly, once somebody cares they have a chronic disease, they need to know what to expect when they actually do a healthy lifestyle and enact some of the exercise training recommendations we're going to discuss. And then lastly, as healthcare providers in every field, we need to know how exactly we want to deliver this exercise prescription. And for the exercise physiologists on this call, some of this you may already be familiar with based on some of the statements ACSM has released. But let's talk about our first question here and talk about how we get our patients to buy in. And before we do this, we'll talk a little bit about that alphabet soup, if you will. And about a year and a half ago, last summer, the terminology for this chronic condition was changed. And for 20 to 25 years, we called fat in the liver, non-alcoholic fatty liver disease. So this is patients who did not drink alcohol excessively and through abnormal metabolism and genetics and an unfavorable environment ultimately deposited fat in the liver. And the reason this terminology was changed is that one, it was a negative diagnosis, right? It has the word non, the word alcoholic is also stigmatizing, right? People don't feel good about themselves when you label them with this. And same thing with fatty. So we as a liver community wanted to feel more inclusive, more sensitive. So that drove some of this. And then also metabolic dysfunction is a hallmark of this condition. So speaking of metabolic dysfunction, what exactly is mazzled? Well, so it's when you have at least 5% of your liver full of fat, which we call steatosis. And you have to have at least one cardiometabolic criteria, which are shown here. And probably not surprising to the audience here when you're doing screenings as exercise physiologists or getting these routine clinical parameters in the endocrinology clinic. And how common is this? Well, individuals living with mazzled actually have a lot of friends, about one out of three people worldwide actually have this. And that equates to about 2.5 billion individuals. Here closer to home in the United States, it's about 80 million adults. And no, not surprisingly, this costs the healthcare system quite a bit. And if we don't intervene early, people can actually progress to end-stage liver disease where they develop cirrhosis and complications of it and primary liver cancer. And now mazzled is actually a leading reason for life-saving liver transplantation. Now, besides the fact that the disease may progress to end-stage liver disease where people have a liver-related death, why else should your patient care they have this condition? And in general, they don't have a symptom that says, yes, I have fatty liver disease with abnormal metabolism. So shown here is data from my good friend, Tracy Simon at Massachusetts General. In figure A, we can see that compared to population controls in red, individuals living with what was then called naffled, which again, now called mazzled, again, alphabet soup, right, have a lower overall survival, okay? And then greater mortality as the figure shows. In figure B, we see a dose-dependent response whereas people's liver disease gets more severe with simple steatosis, meaning just fat in the liver but no inflammation in yellow. It was then called NASH, without liver fibrosis, so inflammation in the liver but no scarring, in green, followed by more death with folks who had fibrosis in the liver but hadn't progressed to cirrhosis yet, which is end-stage liver disease, and then cirrhosis in purple. So why exactly do individuals living with mazzled pass away more often than the general population? Well, it's not always about the liver, and in fact, the leading cause of death in this population is cancer outside the liver. And this is followed by complications from cirrhosis, or end-stage liver disease, and then cardiovascular disease, and also primary liver cancer or hepatocellular carcinoma. Now, another reason we wanna talk to our patients and convince them to buy in is it's, you know, one thing for us to say, hey, you know, you're gonna die early, but it's gonna take some time, right? So on a day-to-day basis, you know, what is another way to get buy-in? And, you know, I said there's not one specific symptom which will clue us into the diagnosis, but, you know, when you look at how people actually feel, individuals living with mazzled actually have the worst health-related quality of life when you compare them to other chronic liver diseases, including viral hepatitis B and hepatitis C, shown here by the dark blue and the gray boxes. And, you know, the FDA recently approved, conditionally approved a medication called resmediram. For the endocrinologists here, you may be aware of this. It works through thyroid hormone receptor beta. But, you know, even though we have a medication now for the first time, you know, lifestyle intervention, including exercise training, is really still gonna be our foundation. And in fact, many payers require patients to be enrolled in a lifestyle program prior to starting this medication. And speaking of lifestyle and exercise, right, you know, we're gonna talk a little bit about the benefits. So hopefully I gave you some things to take back to, you know, people you're interacting with, with mazzled to convince them that they really should care about their abnormal metabolism and their liver disease. But let's move forward and let's talk a little bit about some of the benefits of exercise. If we're gonna, you know, help people to do it, we need to tell them why they're gonna get better. And shown here is a very nice schematic. Exercise really has a wide range of benefits, both within the liver and outside the liver. The good news is most of these are actually a weight neutral intervention. So meaning you can achieve these, you know, with a 3% body weight loss or less. And we're gonna go through each one of these in terms of how it relates to the liver and mazzled. And, you know, shown here is perhaps one of my most favorite slides in our presentation. And this is data from our published Nashville study from several years ago, at which we enrolled 28 individuals. They went through a 20 week moderate intensity aerobic exercise training program. And shown here is the corresponding improvement in cardiorespiratory fitness in figure A. But in figure B, we can see that, you know, nearly one out of two people actually achieved clinically significant improvement in aerobic fitness. And, you know, we define this as a gain of 10% or greater, because this correlates to a reduction in overall mortality of 15%. So I'll say that again, just by getting 10% more fit, people reduce their chance of dying 15%. And I tell my patients this all the time, it's very motivating for them. But what about the liver itself? Well, we published a systematic review and meta-analysis several years ago in the American Journal of Gastroenterology. For those of you who don't routinely, you know, look at these, you know, each individual study here shows the magnitude of effect. We can see it's all favoring exercise because it's over on this side. And then we have the diamond at the bottom with the pooled measure effect and the summative measure here. We can see that exercise training leads to clinically meaningful reduction in liver fat three and a half times more often, and at thresholds that would be expected to improve the liver under the microscope, which is important because this is what drives outcomes. Now, speaking of the liver under the microscope, you know, when we lose fat in the liver, the next thing is that the mash, the inflammation becomes less active. So can exercise do this? So shown here again is data from our NASHVT study. And we can see in figure A that exercise reduces a liver enzyme called ALT at the threshold that would be expected to reduce mash activity. In figure B, we can see that there's a corresponding reduction in cytokeratin 18, also a marker of mash activity and a paradoxical increase with standard of care where the patients just met with us in clinic throughout the study once a month. And then in figure C, we can see a composite of multiple different tests called the mash resolution index. And looking at this, you know, predictive summative biomarker, we can see that exercise training is three times more likely to resolve the inflammation in the liver. And when we look at the cascade of benefit, you know, the first thing we want to do is lose fat and then improve inflammation. The next thing is the scar tissue that fibrosis should get better. And at least at this point in time, you know, we think that you have to lose weight to get fibrosis reversal, but our group is challenging this dogma. We have some translational data here, you know, qualitatively and quantitatively on the screen showing markers of stellate cell activation are improved with exercise. And the stellate cells are the ones responsible for fibrosis or scarring in the liver. So, you know, hopefully more to come on this story as we explore this more, but, you know, for now we know exercise reduces liver fat and improves the inflammatory activity. And then it even can resolve that inflammation and, you know, over time, hopefully we'll be able to show data about liver fibrosis. All right, so what else happens when you exercise outside the liver? Well, it turns out your body composition gets better. Many on this conversation today probably know this with changes in visceral adipose tissue. And, you know, the reason this matters is because when you look at population data, we actually see lower oncologic risk across many cancers that are common in masle. And we think that changes in body composition actually mediate this. And if you're more physically active, your cancer risk is much lower. And, you know, if you're more physically active, you know, people tend to have less adipose tissue, which is in itself, you know, oncogenic. Other benefits are a reduction in cardiovascular and metabolic risk. I'm going to move a little quicker for time here. And then, again, we talked that patients feel poorly with this disease and with exercise training, again, showing data from the Nashville study, I hope you can appreciate that exercise improves every domain of health and people are going to feel better, you know, with sleep disturbance, pain, fatigue, depression, social roles, function support, and cognitive function. So really it is the magical treatment in my opinion, but, you know, of course I'm biased. All right, so, you know, in the remainder of our time together, we're going to go over how we best prescribe exercise. You know, now that we've talked to our patients, convinced them to care they have this, we've told them the benefits, now we got to tell them what to do. And whenever we do this with a behavioral intervention, you know, we want to have a framework. And, you know, this is to make sure we deliver the intervention the same way every time. So one that is very common in behavioral research is called the SBIRT framework, where S is screening, BI is brief intervention, and RT is referral for treatment. And this is all summarized in the recent round table report and guidance from the American College of Sports Medicine, but ACSM makes it very easy. And they say all patients with measles should be screened for physical activity, and they should be screened every time they touch the healthcare system with an interaction with a provider. And if we're going to recommend universal screening, right, you have to have a tool that is going to be easy to do and cost effective. So ACSM published the exercise vital, physical activity vital sign, excuse me, several years ago with work from Bob Salas. It's a simple, you know, two question questionnaire. And when you multiply the values here, you get the total minutes per week. For those of you who want to download this there's a QR code accompanying on the slide. And the nice thing is this is actually incorporated into the electronic medical record. So we can use this really as the six or seven vital sign if you consider paying a vital sign on the clinic. Now, once you screen your patient and you know what they're actually doing, which typically is not the amount we want them to do, the next question is, you know, why are they not doing more activity? Remember, you know, only 10% of people are going to be meeting guideline based amounts of activity with measles. So, you know, we have an internal survey that was developed several years ago and asked patients, you know, barriers to exercise. And not surprisingly, it's similar to other, you know, research where patients tell us they don't know how to do it. They don't have the time, exercise hurts, or it costs too much. The other part of screening, once you know what your patient is doing or not doing and what the barriers are in providing them being healthier is what can they actually do? And, you know, not everybody's going to go through formal graded exercise treadmill testing to figure out their VO2 max. You know, we've all seen Liz's workout videos, so she'll probably do it, but, you know, other folks in your clinic are probably not going to have access to those resources. So, you know, luckily researchers at Duke, you know, about 15-ish years ago came out with the Duke Activity Status Index, this simple questionnaire, which is also cheap and cost-effective, approximates VO2 peak just by looking at activities people do, you know, sometimes even on a daily or weekly basis. All right. So we've talked about the behavioral framework, right? We talked about screening for that SBIRT, the next part is brief interventions. So, you know, what do we actually do? Well, again, ACSM reminds us we should tell everybody with MAZLED that physical activity is good, but as a healthcare system, we're not doing a good job. Shown here is data from the UK and Quentin Anstey and his group, and actually only three out of four physicians talk to individuals with MAZLED about leading a healthy lifestyle. We're even more poor at referring people to dieticians. We're only one out of two patients see a dietician for nutritional counseling, and then exercise professionals, only one out of 10 of us actually refer. So if we're not gonna be sending patients for exercise prescription development from professionals, we need to have a tool. So, you know, we've developed a MAZLED exercise prescription form where literally you can just circle what you want them to do and hand it to them. And, you know, this day and age where things are so technological-based, Patients really love having that paper when they leave the clinic. But if we're gonna circle things, right, we need to know what to do. And, you know, we have the five principles of exercise prescription, which folks are probably well-versed on on this call, but ACSM does have mazzled-specific guidance. It's in the recent edition of the, you know, General Exercise Testing and Prescription from ACSM. And it's similar to other metabolic populations, you know, aerobic activity, three to five days a week, coupled with two days of resistance training. Your intensity needs to be at least moderate to vigorous. And then in terms of time, it depends on the activity, 75 minutes per week of aerobic activity if it's vigorous, or 150 minutes per week if it's moderate intensity. And then the corresponding sets and repetitions for resistance training are listed here, depending on what your goal is, whether it's muscle strength or muscular endurance. In terms of type of activity, right, it's fairly self-explanatory. Aerobic or prolonged rhythmic activities and resistance training, you know, it doesn't have to be done at a gym with free weights. Certainly body weight exercises are sufficient. We'll talk a little bit now about why ACSM makes each recommendation. Well, in terms of intensity, moderate is much more effective than low. Shown here is another systematic review and meta-analysis comparing moderate intensity to low-intensity activity in the impact of liver fat. And I hope you can appreciate the diamonds on the left here showing moderate intensity is much better. In terms of exercise type, the best type here is gonna be in the upper right-hand corner. So you can see resistance training plus aerobic training, for which there are very few combination studies, actually wins out, you know, followed by each one of the individual things here. Dr. Keating has done a lot of work in high-intensity interval training, and perhaps we could ask her some questions during the Q&A. So I'm not gonna touch on that too much, but whenever we deliver an exercise prescription and we use these elements of the FIT principles, we're really trying to deliver a dose, right? And you may say, you know, John, what is exercise dose? I know what a drug dose is, you know, where we take the strength of the medicine, such as metformin, 500 milligrams, and then we give it to a patient, how often? So BID, twice a day. And we want them to take it every day, and then we recess response. You have three months where we look at their blood sugar control with a hemoglobin A1c. Now we can do the same thing here with exercise dose. We're looking at intensity. So how hard people do it, you know, frequency, how often, and time. And then we arrive at this magic number that we tell people to do, which is about 150 minutes per week of walking, or the equivalent of 750 minutes per week of activity. And you may say, well, that's great. Where did this number come from? Well, when you look at people who do this amount of activity versus those who don't, I hope you can appreciate in the dark blue bars that people have a much greater reduction in liver fat at clinically meaningful thresholds. And in fact, you're more 60% more likely to achieve the response we want when you do 150 minutes per week of walking. Now, I realize this is a ton of information in a short time period. You're not expected to remember everything. There's no test at the end. But if you want something to hand your patients, ACSM has this from Exercises Medicine. Again, a QR code here. And we give this to every patient in clinic just to reinforce, you know, what we tell them. The other thing is I'd like to encourage everybody to engage exercise specialists, perhaps in preaching to the choir. ACSM says you should recommend, or, you know, consider this raw with mazzles, and especially for those who are not, you know, meeting the recommended amounts of activity. And, you know, the exercise specialist can help the physician quite a bit. I have several preferred providers, even one on my research team, and, you know, rely on them to really augment the clinical care I provide during a 20-minute visit. And if you are looking, you know, for ways to identify exercise professionals, ACSM has a database, Profinder, several folks on this call today may be in there. And we actually direct patients in our clinic to this if they're looking to find somebody, or even sometimes actually help them if they ask nicely. All right, but let's get back to our patient, okay? We've gone over quite a bit. You know, we went over that, you know, mazzled is common, and it costs a lot, and people die early from a lot of different things. We talked about how exercise improves not just the liver, but metabolic risk, and cancer risk, and quality of life. And then we've gone over how we want to prescribe exercise to exert this benefit. But what about our grandmother? What actually happened with her, okay? So, you know, by three months, you know, she was doing well. Like many of our patients, she struggled with consistency in the beginning, but she did get to that guideline-based amount of aerobic activity. And then she was supplementing this with two days a week of resistance training. And, you know, when we saw her back at six months, she had a very modest, you know, weight loss, which was expected. She said, you know, I don't really want to focus on diet right now. I just want to focus on the exercise piece. And when we measured the fat and the stiffness in her liver with that ultrasound technology called FibroScan, we can see that it's much better. The liver fat went from grade three to grade one. The stiffness went from one stage of scarring to an earlier stage. And then you can see the corresponding improvement in her metabolic risk parameters. But, you know, the thing that really warmed my heart is on the way out the door, she was like, look, can you stop talking? Now we have to go home and exercise. The visit with you today is during my exercise sessions. So clearly she bought in and was motivated. And, you know, again, I'm happy to take questions after our second speaker. A lot of the research today is through the volunteerism of hundreds of patients and hundreds of people on the research team here at Penn State and throughout the world that have worked together. So, you know, thank you to everybody from the bottom of my heart and I'll turn it back over to Dr. Keating. Thank you. Thank you so much. So thank you so much, Dr. Stein, for that incredibly comprehensive and really informative presentation. So it's now my pleasure to introduce the second speaker for today. In 2021, Ms. Kerri Sivier was diagnosed with Matildia MASH, autoimmune hepatitis, primary biliary cholangitis and cirrhosis. These diagnoses set her on a journey of learning and adaptation guided by her medical team. Through medication and lifestyle changes, she lost 110 pounds, which helped eliminate fat in her liver. She has faced many challenges and victories throughout her journey. Through the inspiration of her care team, she strives to be a model patient. Kerri's goal is to continually improve patient outcomes through education, advocacy, and telling her story. Today, she'll present on her personal experience, information shared from her hepatologist and the importance of a comprehensive care team. She will address common feelings and questions patients may have after diagnosis, as well as strategies for providing resources and encouraging open communication. Additionally, she'll emphasize the role of realistic lifestyle changes, including nutrition and exercise in achieving successful treatment outcomes and long-term health. Thank you very much, Kerri. Hi, thank you for having me. I'm very pleased to be here today. Again, my name is Kerri Sivier. I was diagnosed with these in 2021. I have Mazelden Mash, which was caused by autoimmune hepatitis and primary biliary cholangitis. And as a result of those things, I also have liver cirrhosis. If you want to go ahead and advance the slide. And so what I've been doing, I am lucky to be part of a multidisciplinary clinic. And this is a fairly new practice from what I understand, but my disciplinary clinic does have my hepatologist. It also has my endocrinologist and my dietician. And I've also committed to making the lifestyle changes, including diet and exercise. And again, I did receive a 100, I'm sorry, I did achieve a 110 pound weight loss and I no longer have fat in my liver. I do still have mash because of the cirrhosis. So that's not going away, but I have slowed the progression of my liver conditions. And if you want to go ahead and advance the slide, but that picture that on that first slide was me at 315 pounds approximately. And then the last picture was taken this past May when I was the Chicago 2024 liver life champion for the American Liver Foundation. And I'm now about 200 pounds. So, and I'm five eight. So for what that's worth, make a difference in my BMI. My core care team does consist of the three professionals that I've already mentioned, my hepatologist, my endocrinologist and my registered dietician. But I also have seven outside professionals or approximately seven. My general gastroenterologist, my psychologist and my primary care physician are just a few, but I also have general care, such as things like dentistry and vision, which also are an important part of the health for a massive patients. And something that I don't have, but I think would be beneficial possibly it would be a physiologist because physiologists can create a safe place where you can make an effective exercise plan that's tailored especially to the patient's needs and to help them stay active, which is really critical for weight loss and overall health. And if you wanna go ahead and advance the slide. So I do wanna also note that we don't know why I have these things specifically. I did have obesity, but with the autoimmune hepatitis and primary biliary cholangitis, which were also contributing factors to my Maslod, there is no finding out why we just can't go back that far in my medical history. There's no way to trace that. I didn't have signs or symptoms. One of the things about liver disease is you often don't have signs or symptoms, except for when I had swollen ankles, which then I found out that I had liver disease. And it's also worth noting that there is a benefit in having a symptom, even though it doesn't seem like it, because a lot of times patients who don't have symptoms also don't find out that they have liver disease until it's far too late. We're talking about when we're in the stages where they've got hepatocellular carcinoma, where a transplant is absolutely necessary at that time and as soon as possible. And I also wanna talk a little bit about resmedarone, which is something Dr. Stein mentioned. I have to say, I'm really excited about that, even though I'm not eligible for that at this time because of my cirrhosis. I know that they are doing clinical trials for that. And it's exciting because it is a marvel of modern medicine and the testament to what we've done so far. But it's also important to know that like any medication, you can out eat it. And it does need to be used in conjunction with lifestyle changes in order to be most effective. It's also like ozempic, which I'm also on because I was on a steroid that put me into diabetes. Rarely, but ozempic does also help with the weight loss component, which also benefits mazel-de-mesh patients. Oftentimes, when patients are on these semi-glutides, it is also in conjunction with healthy lifestyle changes. And my team gives me those tools that I need to make those healthy lifestyle changes. So the reason why my team helps, like I said, is because they give me those tools, but each person brings their expertise, ensuring all of my aspects of my disease and its related conditions are addressed. I have a statistically improved chance of outcome. Studies show that coordinated care like mine leads to better liver disease management, reduced complications, and a better quality of life, which I can speak to directly because my life has improved many times over because of the lifestyle changes that I've made. I have more energy. I just have a much better physical feel overall. And I was able to get a personalized plan from input from my different specialists and a tailored plan that works individual needs and goals. I will say that probably, much as my hepatologist has helped and my endocrinologist has helped, the tool that's given me the most success is having a registered dietician. There's just something about that where when a patient has someone to talk to where you can really personalize your own needs and how your own body works with a professional who understands macronutrients and the different types of foods that are needed for patients, that it really makes all the difference. And they also do overlap a little bit with the physiologist that I was talking about, where they'll say, you know, you probably should do about 30 minutes of exercise per day, or here are some different things that you can do. I prefer walking, but you can also use things like a resistance band. So if you want to go ahead and advance to the next slide. So there are a lot of feelings that patients have, especially at the beginning. And for me, that was being overwhelmed. I wasn't sure if I could do this. There was a lot of information being thrown at me at the same time. And then there was also not enough information for me. I received the advice that I needed to lose 10% of my body weight. And I should state that I have actually seen two different hepatologists, as well as I do have a gastroenterologist for my general needs. The first hepatologist who I saw was one of the best in the world. I have the advantage in Chicago where I live of having three hugely competitive health systems, and many of the best hepatologists are part of that. But the advice that I received was, follow the Mediterranean diet and lose 10% of your body weight. And if I knew how to do that on my own, I wouldn't be in this situation. I would have followed a better diet. Even though I have the autoimmune components and I might still have this disease in the end, I probably would not have been as obese as I was. But there was fear. There was fear of what would happen to me. There's still some degree of fear, but I have a lot better control over that now. There was guilt and shame that somehow I had made the decisions to become as obese as I was. And I realized that now, yes, some of that could have been from my own decisions, but also some of that could have been from metabolic factors that were coming into play that I didn't know about. There was a lot of self-pity, a lot of sadness, a lot of anger. Those are things that occasionally still creep in today, but for today, there's mainly hope. And that's because of the care team that I receive the care from. And I also had a lot of questions. What can I eat? What guidelines should I be following in terms of macros? How much or how little fat? How many carbs I have per meal? How much sodium is okay? How much fat is okay? How much exercise do I need? Where can I find support? What options are available besides going to a gym or a health club? And what if I don't succeed? I wanna talk a little bit more about those things in the next slide. So what can I eat? That was, when you just receive a list of what is acceptable in the Mediterranean diet, first of all, it's really confusing for patients because a lot of times it doesn't include the modified version that's recommended for liver disease patients. It's more like the basic diet. And the original version of the Mediterranean diet actually isn't completely appropriate for liver disease patients because it includes white pasta and it also includes red wine, both of which are things that liver disease patients probably should not have, definitely should not have with regards to the red wine. And so when I got to speak with my dietician, she really gave me a clearer picture of what was specifically included and what types of things are also Mediterranean diet adjacent. So for example, fruits, vegetables, those are the primary basis of the Mediterranean diet. But things like bananas or blueberries or strawberries, those aren't necessarily common in the Mediterranean area. So they're not technically considered part of the Mediterranean diet, but they still are healthy for patients. Blueberries offer a lot of antioxidants and fibers which help keep your immune system healthy. Bananas are more on the complex carb side of things than they are on the simple carb. They still will spike your blood sugar. So I know working with a group, with the American Diet Association, I'd be re-recommended and say that like, use this advice with a little bit of a grain of salt because some of these things, because I'm not diabetic, may not 100% apply, but they are a great place. And what guidelines should I be following? And I try to avoid saturated fat and trans fat. I also try to continue to eat healthy fats such as monounsaturated and polyunsaturated fats, those things are great for you. Things with fatty omega-3 in them, such as avocados, are really heart healthy. They actually are kind of known to promote this barrier between forming that unhealthy fat in the liver and creating a healthy barrier that forces the unhealthy fats to go through the liver instead of staying in there, which is great, especially if you are not yet in the cirrhosis phases where you're scarring is permanent and you're still in the reversible phases. Because once you get rid of that fat in the reversible phases, a lot of times the inflammation goes down and you're pretty much as healthy as you would be prior to having Maslow's or MASH. I also stick to whole grain carbs. I like to eat whole wheat carbs. I like quinoa. I like things that are just healthy overall. And I try to stick to 20 to 30 grams of carbs per meal. That's my guideline from my dietician. Again, that might be different for someone who's diabetic. And I also do try to exercise 30 to 40 minutes per day. I've actually found myself going longer than that. I enjoy going about an hour, but I don't always have time for that. And with that, I will say that I do find exercise opportunities in small places. I look for those micro opportunities that present themselves. For example, parking your car in the farthest spot in the parking lot. Doesn't seem real ideal or fun in the beginning, but when you start moving, an object in motion is not easily stopped. And so you're gonna find probably that you really like that physical activity after a while. I will say for me, that probably took about four months when I started noticing results and started feeling those endorphins kicked in. But again, I look for those opportunities in small places. If you have a half hour for lunch and you can give up 15 minutes of your day in your workday, then go for a walk during your lunch, even if that's just up and down the hallway in your building. Or if you work from home, maybe take a walk around the block if you can. It's those little things really do add up. I am a big believer in taking one small thing and making it just a little bit better. That's what worked for me for the beginning. It's not easy to go about these changes with having to go from one lifestyle to another. A lot of us are not in healthy lifestyles when we start this. So doing things like, maybe you eat breakfast cereal in the morning, but maybe you eat like a sugary cereal when you first start out. And those are not ideal, but can improve that. If you eat less sugar or maybe no sugar at all, that's still not making any changes at all. And I worried what would happen if I didn't succeed. And now I try to focus on what's gonna happen if I do succeed. But I would say for patients who do have that worry, the advice is to show grace and show empathy. And that's not just from their healthcare provider, but to encourage them to do that for themselves. We are human beings. We make mistakes. We crave things that are not good for us sometimes. And it's important to listen to what your body's telling you even from an emotional response. For me, again, I try to show myself grace. I don't succeed at this. But one day I'm like, hey, that's all right. I'm gonna hit it the next day. If I can't do it for a week, and there are times when I can't do it for a week because I'll have had a procedure done or something that will like make me feel really awful. It's focusing on what I can do, what I can do to try to maintain my healthy diet, to get myself to a place where I'm feeling better, and then getting back at it. Because getting down and staying down is one thing, getting down and back up is another. And to me, if I'm not down for long, it's much easier to stand back up. And so that's really what I work on is just, again, self-grace and self-forgiveness. So if you wanna advance to the next slide. So for me, lifestyle changes are all about taking a holistic approach. It's body, mind, and spirit. I started by doing many types of, I try to vegetables, fruits, whole grains, proteins. I also like to experiment with spices, but not seasonings too, because those are sometimes sources of hidden salt and sugar for flavor. Something that I use to help me with that is I use AI sometimes. I was using Pinterest. I still use Pinterest sometimes to find recipe ideas, but I found that plugging things into an AI, like a chat GPT or Google Gemini and saying, I have these ingredients at home and I wanna make something with it that has like less than 30 carbs, for example. You can actually plug that in and it'll come up with something for you. And it will come up with a recipe on how to cook it as well. So those tools, most of them are free. And it does open up doors for patients. I also use the same principle for exercises. I tried a lot of different things, but I like walking the best. It's the most versatile thing for me. It fits the best into my schedule. And I really enjoy actually just having that mental escape from the world, even sometimes my liver disease, where to just turn on my music and walk and for an hour, just maybe out just a little bit, not pay so much attention to the surroundings, but pay a little bit more attention to what's going on inside of my head mentally. Again, I give myself a lot of grace. If I go off my diet for a day, that's okay. I forgive myself and I try again at the next meal or the next day. That's another thing that I like to think about and suggest for patients. You don't have to wait until the next day to start over. These things come, these come every time we have a meal or a snack, you have an opportunity to do a little bit better. So if normally your snack was a candy bar, maybe you go for a low sugar granola bar or something like that. My dietician gave me so many of these suggestions in the beginning and I've just stuck with them throughout because they work and they're versatile. For me, one of the things that I like to do is I like to prepare my meals ahead of time, especially my lunch, because that for some reason is the biggest drag to prepare every day for work, but I can make a salad and I can, the salad dress like having a whole different meal. And I allow myself to enjoy food and rest. It's a huge part of our culture that when we go to parties and things that there is food there. And it's not healthy food usually, it's like the birthday cake or chips and salsa or, and that does get bad rap. Chips and salsa actually can be not that bad if you do it the right way. But I take time to just enjoy those things because that's a really important part of this too. If you don't enjoy what you eat, you're not gonna be able to stick with it. That's why it's so important to find recipes that meet patients. So providing the tools that they need, such as a dietician is absolutely key. And that's not something where you wait for them for it. Gotta be part of your program to start out with. There's just, for me, there's no reason not to suggest that right from the beginning. I would want, I would have wanted that advice as a patient. Instead, I had to go out there and find what I thought would be best for me. And I happened to find out that the doctor who I was working with was part of a health system that if you're willing to go a little farther into the city you could actually meet with the dietician and have a diet that's tailored for liver disease. And there are dieticians out there with endocrinology as well, as you know. So wait for your patients to ask for that. Suggest those things from the beginning. If you have those resources available and you're able to, just give it to them. But if I'm tired, I take a nap if I'm able. I assess my cravings. I force myself to wait for things. That's another trick that I use is like, don't give in to those cravings right away. It's not easy, but it can be done with some mental retraining. And if you find that for patients that you're still craving M&Ms or something three days later have the M&Ms and don't feel guilty about it. Indulge those things. Again, I'm not diabetic. So maybe there are sugar-free options that will also help patients indulge in those cravings but do have it, just do it in moderation. That's really a key factor in maintaining the diet portion of this, which is absolutely key. I'm a firm believer in run or out walk your fork. So it starts with the diet and then the exercise is a huge component that will lead you the rest of the way to success. That said, you also can't do this without exercise. So those cravings will go away and then just do better when you can. Use your software to hold yourself accountable and do it yourself. Thank you. Thank you so much, Kerry, for sharing your really insightful and inspiring journey. We'll use the remaining of our time to ask some of the questions from the Q&A panel. So please do remember to post your question in the QA box rather than the chat function if you are posting. And we've had some great Q&A discussions and there's been some talk around exercise dosing and some, I guess, some sound bites in terms of ways to communicate and motivate exercise prescription to our patients. The first question I'll ask for you, Dr. Stein, this is relating back to the data that you're showing on the mass resolution outcomes. How do these differ in lean individuals and do we know whether these differ in terms of the context of body mass or whether there's change or no change in body mass? Are the benefits you're seeing in mass resolution independent of body weight? Yeah, Dr. Keating, thanks for that question. I actually just gave the presentation on that data several days ago in San Diego at a conference and the question about individuals who have normal BMI and are termed lean, lean mass or lean mass, which I hate that term because even though you are technically considered to be normal weight, you have metabolic inflexibility and more visceral adipose tissue which contributes to insulin resistance. So our data for mass resolution was in individuals all of whom had a BMI above 27. So we don't have any data from that in particular. And in general, the literature with exercise looking at that specific population, as you know, is just not there. But when you look at what the leading societies do recommend in terms of a lifestyle intervention program for somebody who is considered to be of normal weight but still living with metabolic dysfunction associated steatotic liver disease, we do still recommend a modest weight loss, about three to 5% because again, we think that is enough to achieve some histologic benefit including mass resolution. The exercise guidance is exactly the same regardless of your BMI. And then in terms of the body composition data, at least I can speak about our studies. You know, we've done largely aerobic based interventions and we see quite a bit of change in body composition. We see reduction in both visceral and subcutaneous adipose tissue. The visceral adipose tissue again is more metabolically unfavorable. So I'm more excited to see those changes. The data is even more compelling with high intensity interval training in terms of the reduction in that fat mass, which is what drives a lot of the insulin resistance and some of the cancer risk. But our aerobic protocols didn't really change fat-free mass they maintain them, but certainly if you have the right type of resistance training, such as what Kerry was talking about with some of the band-based exercises, people can improve some of their lean body mass. Yeah, thanks very much for that answer. And I guess that extends to, what should we be focusing on, clinicians providing information. So, as Kerry mentioned, some of the key outcomes of Kerry, your journey was increases in energy and just the overall physical feel. So these are often, I guess patient important outcomes that are beyond things like weight, but we often have a very large focus on weight loss in our messaging. Do you think that should change? And how do you think that should change from a clinician perspective? I think it's important to focus on health first and weight loss doesn't always mean health. So focus on doing things like making sure that your patient's blood glucose levels are where they're supposed to be and that their A1C is where it's supposed to be. And I think oftentimes the things that lead you to the good A1C and good blood glucose levels are going to be the same things that lead you probably to a weight loss outcome. And it's a lot easier to do weight loss when your body isn't working against you. So focused on getting health first and then weight loss, but I actually don't think weight loss should be the primary focus. I think it's overall health. Yeah, thanks for sharing that. I think that's probably a message, Dr. Stein, that you would agree with. Yeah, absolutely. I was going to say, I mean, it's so great to have Kerry here to share her journey and congrats on all the success that you've had and everything you've done to take charge of your health. It's so inspiring and want to book you to come talk to my patients. I think if they see what you're doing, they're going to be even more motivated. And it's so great you have access to a multidisciplinary program. But you talked about feeling overwhelmed, right? Overwhelmed with information, but not helpful information. And I think sometimes by the time somebody sees a specialist, they've already heard to lose weight, right? They've already heard to go exercise and the diet and the message has to be different, I think, when you get in that environment and be one that is supportive and provides meaningful information. So it's always good for us to hear, what actually do you want to hear as a patient? What is well-received? How should we be making sure we have sensitive messaging and one that is going to be effective, right? And I think the important thing here is this is not just a one-off visit, right? These are lifetime relationships, at least that's how we approach it in our multidisciplinary program. We want to be your doctors for the rest of your metabolic journey and making sure we have consistent messaging and then information that's helpful over that journey is really important. So again, thank you for sharing and you're speaking all the things that are in my heart. So thank you. Thank you. Well, thanks very much. We're actually almost out of time, unfortunately, because I think we could probably discuss this for a lot longer, but hopefully from today's talks, two excellent presentations, two different perspectives that really I think we can link together to carry forward in both research, but also clinical practice and how we really convey messages and work with patients to encourage them on their healthy lifestyle journey. So I'd like to thank everyone for attending. There's been a lot of great resources that have been mentioned. Hopefully you can take some of those pamphlets and information sheets that Dr. Stein's presented and bring them directly into your clinic. So I guess I wanna leave the last minute to again, thank Dr. Stein and Kerry for your incredible talks. They've been really fantastic and we've learned a lot. So thank you very much. Thank you. Yep, thanks again for having both of us. This was a delight.

MASLD

exercise

lifestyle interventions

liver health

personalized care

multidisciplinary team

health outcomes

patient counseling

metabolic risk