Hello and welcome everyone, on behalf of the NAFLD Special Interest Group, I'd like to thank everyone for attending today. And this is coming from the NAFLD Special Interest Group Steering Committee, and we're hoping that this education will help you in your practices. Also if you have any ideas for webinars in the future, feel free to email us. Today we have a unique format that we have three international speakers that they will answer questions about dietary recommendations. If you have questions, there's a Q&A box, please feel free to send a question there and we'll try to answer it at the end. So the topic is dietary recommendation for NAFLD patients. We all have these patients come to our clinic, we do this every day, so let's see what's the evidence-based medicine and most updated literature. With that, the first question we have asked Professor Manuel Romero-Gomez to answer is how much weight I should lose. So let me introduce Professor Manuel Romero-Gomez. Manuel Romero-Gomez is from Seville, Spain, he's a professor of medicine, he's the head of the Group for Translational Research on Liver Disease, Institute of Maya Medicine of Seville. He coordinates the Spanish Registry of NAFLD and NASH and coordinates the ESIL-supported European Registry for NAFLD. He's principal investigator in the Spanish Network for Research in Digestive and Liver Diseases. Very importantly, he's very widely published in the area of NAFLD and NASH, and one of the landmark paper answering that question, how much weight I should lose, comes from Professor Romero-Gomez's group. Looking forward to hearing you talk, Professor Romero-Gomez. First of all, I would like to thank Dr. Mazen Nureddin for inviting me to participate in this webinar. It's very exciting and fascinating to spend this time together with all of you in this very hot topic. My topic today is trying to discuss the obesity and the metabolic dysfunction in NAFLD, the impact of losing weight in NAFLD, and how to lose weight and how much weight should I lose. Obesity is a major risk factor and is underlying the majority of the metabolic alteration in the Spanish EPAMET registry, including more than a thousand patients with liver biopsy, and you can see when we stratify patients according to different risk factors, how obesity is present in the 50%, at least, to 90%. The majority of the patients with NAFLD show obesity as a risk factor. When we divide patients in obese and non-obese with metabolically healthy or unhealthy, you can see how the majority of the patients, more than half of them, show obesity metabolically unhealthy. The key point is we can have a very big overlap between obesity and the rest of metabolic risk factors. In this study from Eduardo Villar-Gomez in Cuba, they must say that the percentage of weight loss is the key factor predicting response in patients with NASH demonstrated by liver biopsy. Here, including 293 patients, NASH resolution was found in 90% of the patients when weight loss was higher than 10%, fibrosis regression in 45%, and histiodosis in 100%. The main problem was that just 10% of these patients for one year working in a multidisciplinary approach with a psychological approach with a hepatologist, etc., we cannot reach a successful response in more than 10%. This is the main reason by which we need to improve this aspect, and here you can see how the percentage of body weight that you lose is very important, impacting both in NASH resolution and in fibrosis regression. Here you can see when you lose more than 10%, you have no guarantee to regress fibrosis because some patients keep stable, but you did not worsen, you did not impair fibrosis to state that this is a key point. If we promote weight loss, we can resolve NASH, we can resolve histiodosis, and we can regress fibrosis, but in the case we are not achieving that, we can preclude worsening of the liver disease. When we analyze which are the factors predicting NASH resolution, again, weight loss was the major factor together with AD normalization. When we are treating our patients, we need to focus on these two key factors, the percentage of body weight that you are losing and the normalization of AD, taking in mind that normalization means lower than 30 in males and 90 units per liter in females. Of course, we need to take into account that some groups of patients, older patients, type 2 diabetes, more inflamed patients, they are more difficult to achieve NASH resolution. At the end of the day, obesity is extremely linked with the rest of the risk factors and when we treat obesity, we can impact on type 2 diabetes, on arterial hypertension, on dyslipidemia, and insulin resistance. That means we are touching the key point in the pathophysiology of NASO. Therefore, NASH therapy is based on weight loss. We can try to weight loss by diet and by physical activity, but the key point is the diet. Of course, we can modulate the calorie restriction that seems to be crucial in the development of a diet able to promote weight loss. We can use low-calorie or very low-calorie diet, but also we need to keep in mind the role of macro and micronutrients and also the circadian rhythm like the intermittent fasting that could be helpful in some cases. Physical activity is very important. It's a complementary action and as we can discuss later, we need a multidisciplinary approach, but also we need to add to any action promoting weight loss because the beneficial of the physical activity is strongly linked with weight loss. Using Mediterranean diet, you can promote weight loss of minus 3.7%, less than 5%, and the percentage of patients losing 5% is around a third versus 10% in the control, in the non-intervention group, and the weight loss higher than 10% is 7% versus 2.2. 7% is close to our 10% that we have in our study. This Mediterranean diet promoting this weight loss that is not enough to reach a natural solution for fat loss and degradation could impact on cardiovascular factors and also improving glycemic control. Therefore, we need to implement Mediterranean diet because we can improve the liver, but we need to add a calorie restriction and energy restriction to promote improvement in the liver. One possibility is to add exercise, but we have enough information on the literature that exercise by itself is not enough to promote weight change. The majority of the patients keep the same stable weight and in this meta-analysis, you can see how the beneficial effect of physical activity was linked in the group that underwent any other intervention promoting weight loss. In the upper part of this slide, in patients without weight loss, we cannot improve liver disease. At this time, the ASOV recommendation in the guideline is exercise alone in adults may reduce hepatic osteoporosis, but its ability to improve other aspects of the liver is solid and remains unknown, and it seems that we can reach that when adding to weight loss. Therefore, we need to keep in mind that we are not just talking on patients on NASH and NASH significant fibrosis, even in patients with advanced fibrosis and cirrhosis, weight loss together with physical activity improve cardiorespiratory fitness and the quality of life in these studies, and at the end of the day, we can promote weight loss and this weight loss was associated with improving HBPG with 24%, a quarter of the patient showed reduction in HBPG when losing 10% of the body weight. This is very important to keep all this in all the spectrum of patients with liver disease. In summary, in this parameter of weight loss, we need to keep in mind that using diet and physical activity, we can improve the metabolic profile, we can promote weight loss, and putting together this effect, we can improve hepatitis, promote NASH resolution and fibrosis regression. We can need to lose at least 10% to improve fibrosis, losing 7% we can improve NASH resolution, it's much higher when losing 10% but 7% could be enough, losing 5% we can improve ballooning, inflammation, and losing 3% or more we can improve osteoarthritis. The main problem is the percentage of patients achieving these goals, lower than 10% in one year lose 10%, lower than 20% lose 7%, and 30% lose 5% of body weight. That means that when we implement a lifestyle intervention in this patient, we need to keep in mind that if the lifestyle fails, we need to promote drugs and therapy. Here you can see several drugs that are being approved by FDA to treat overweight and obesity. If the drug doesn't work, we need to use endoscopy from the gastric balloon to a sleepless surplus sleep. Recently, the duodenal mucosal resurfacing, it did not promote very large loss of weight, but it could be complementary to the other one to improve liver disease, and if the patient is non-responder to endoscopy, we need to move to surgery by gastric bypass, the most common surgery is the sleep gastroplasty by bicep surgery that promotes very important weight loss that we keep over the time and we can promote resolution of NAS and fibrosis regression. Finally, just to keep in mind that all patients are individual, are different, and we need to study as much as possible to reach as much information as possible to have the data on the omics to promote a precision medicine to use artificial intelligence and computational analysis to design a personalized diet, a personalized physical activity, a personalized intervention in this patient with NAFLD. Just to finish with my comment, yes, obesity is a major risk factor, it's only related with the metabolic dysfunction and was implied on the development and progression of NAFLD. Losing weight did improve liver injury, did not guarantee fibrosis regression, but predicted fibrosis worsening. The target should be losing 10% of body weight, 7% could be enough, but losing less than 7% could not be sufficient to promote NAS resolution and fibrosis regression. If lifestyle fails, we need to implement drugs, endoscopy or surgical bariatric surgery to promote weight loss and supervised exercise and diet in child A and B cirrhosis seems to be safe and can be considered in selected patients to reduce weight and improve cardiorespiratory fitness together with liver function and portal hypertension. Thank you very much for your attention and I would like to thank all people belonging to our group, the Cell Liver Group in Seville, for all the work that we have been doing in the last few years. Thank you. Thank you very much. Thank you so much, Professor Romero-Gómez. That was brilliant. I'll keep the 10% in mind, aim high, and understand my patients cannot achieve it. So 7% should be enough. The next question we have asked Dr. Long is which diet I should follow and which food I should eat. So I'm sure all of you, they have these patients that they come to clinic and they have a list of, I personally have a few patients like, should I eat avocado? Should I eat tomato? Should I drink coffee? Should I do this and that? There is actually evidence-based medicine behind this and Dr. Long is going to walk us through this. So Dr. Michelle Long is a clinical investigator and hepatologist at the Boston University. She is the director of the Boston Medical Center Non-Alcoholic Fatty Liver Disease Research Center. She's also the director of clinical research for the section of gastroenterology and hepatology in the Department of Medicine, widely published on NAFLD and NASH and funded by the National Institute of Health. It's my privilege to present her and I'm looking forward to listen to her talk. Great. Thank you, Dr. Nardin. So which diet should I follow? We're going to go through the different macronutrients and I gave a talk a few years ago and updated this talk today and there have been some updates and some new emerging evidence. So what about fat? Fats are calorically dense and they do not promote satiety. NASH patients consume more saturated fat and less polyunsaturated fat and fiber compared to controls. Recently we've seen that cholesterol intake associates with NAFLD and NAFLD serosis. That leads us to omega-3s. We know that they reduce lipid accumulation, improve insulin sensitivity and have anti-inflammatory effects. There were some really promising meta-analyses that showed possible benefit of omega-3 on liver fat. However, several randomized control studies did not show improvement in NASH histology. What about carbohydrates? As we know, carbohydrates are quickly converted to fat stores and are added to many foods. So this is what I mostly focus when I'm talking with patients. We know that sugar, sweetened beverages are associated with NAFLD and that fructose upregulates hepatic de novo lipogenesis and is associated with fibrosis. So this figure here is from a cross-sectional study in the NASH CRN that looked at people with greater than or equal to seven servings of fructose per week. And they had a much higher adjusted odds ratio of hepatic fibrosis compared to those that consumed less fructose. And finally, protein, high protein diets, they're associated with weight maintenance and promote satiety. They're very much in vogue as well, but we do know that individuals with NAFLD consume more animal protein compared to those without NAFLD. In a study recently published from the Rotterdam Population-Based Study, they had about 3,000 participants with NAFLD and they found that high animal protein intake was associated with NAFLD only in individuals that were also overweight and not in lean individuals. And it seemed like total, you can see from the figure here, the odds ratio, if you were in the highest quartile versus the lowest quartile of protein intake was associated with NAFLD for total protein and animal protein, but it was not technically significant for vegetable protein only in those that were overweight. So which diet is best? We heard about weight loss and that really is the key here. So if you can lose weight, that's really what is going to help with your liver as far as we know. There's really a paucity of well-designed nutrition studies. There are a few longitudinal studies and most are limited by short durations of follow-up, small sample sizes, and lack of objective measures of liver fat. So there's a lot of work to be done and really great opportunities to improve our knowledge in this area. The Mediterranean diet, well, there are several small studies that show reduction in liver fat. It's the diet recommended by EASL, the European Diabetes Association, and so it sort of hits a lot of the high points in terms of high fiber, low in red meat, and low in added sugars. So it's a good place to start. What about low carb, low fat, intermittent fasting? There's some evidence that's limited to small studies that show some possible benefit for liver fat reduction. So stay tuned, but they're not ready for prime time. But if they work for your patients and they're losing weight, go for it as far as I'm concerned. So what food should I eat or avoid? Well, this is from Dr. Nordeen's recent study in hepatology, looking at a case-controlled study design in a multi-ethnic population-based study. And they looked at red meat consumption, poultry, and other different foods. And the odds of knock-folds was increased by the quartile of red meat consumption. So this would be in support of considering a limiting red meat consumption or a more plant-based diet. There were similar trends for poultry consumption, although this was about 3000 participants with NAFLD and about one sixth of those had cirrhosis. And we saw similar trends for those with NAFLD cirrhosis, increasing odds of NAFLD cirrhosis with red meat consumption but not for poultry consumption. Interestingly, dietary fiber was protective against NAFLD. Fiber is good for you in general. And so another reason to recommend fiber. This hasn't been seen in all epidemiologic studies, so we need additional studies to confirm. I spend most of my time talking about sugar. So I always recommend to my patients to follow the dietary guidelines for Americans to consume less than 10% of calories per day from added sugar. The biggest sources of sugar in our diets are sodas, sports drinks, cakes, cookies, candies, ice cream, all the good stuff. But there's also many hidden sources of sugar. You can go to Whole Foods and spend a lot of money on organic this and that, granola bars and yogurts and things like that. And if you read the labels, you'll see that they're full of sugar. So I spend a lot of time talking to my patients about what they're eating in between meals, what's their vice, and then we talk about ways to get around it. And we also spend a lot of time going over how to figure this out. So we can say, okay, you need to have less than 200 calories per day from sugar. What does that mean? So in my lab coat, I have a teaspoon measure, I have a tablespoon measure, and I show them, look, a tablespoon is the serving size for ketchup. In every tablespoon of ketchup, there is one teaspoon of sugar. It's pretty shocking when you put it into that, especially when people eat generally way more than a tablespoon of ketchup at a time. We go through how you look at a nutrition label. You need to understand where the sugars are under the total carbohydrates and how they're broken down. Also, how to read the ingredients. In this example here, we see sugar listed, but then there's also dextrose, and that may not be recognized by your patients. They may not know that that's sugar. So I tell people to look at the ingredient labels and just make sure there's no sugar in the first three ingredient in anything that they eat. And also to kind of keep track of their total sugar intake and make sure they're not having more than 50 grams of sugar a day. And kind of keep those visuals handy, whether you bring sugar cubes into your office or you have the measuring spoons available to show them what these mean. I think it's pretty eye-opening. Other tips that I go over with my patients, you know, we talk about what do you like to eat? If you like to eat ice cream, then we talk about, hey, how about you buy blueberries, put them in the freezer and eat them frozen? Or put yogurt in the freezer and eat it frozen because it's much, much healthier. So you can add fruits, fresh, frozen, dried, canned, instead of adding sugar, syrup, honey, molasses, things like that. Drinking water, getting off of the sodas. I mean, I love it when patients drink soda because it's so easy to miss them not to. But water is much better. Reading those food labels, understanding where sugar is hidden, and making sure that you're not buying quote unquote healthy food that's loaded with sugar. If you like cookies and cakes, I tell my patients that you need to bake your own and not buy store-bought items. And then you can easily just cut out half of the sugar in the recipe or replace it entirely with applesauce and really not change the final product. You can add spices instead of adding sugar or vanilla adds a lot of flavor, you know, to a smoothie, for example. And without adding extra sugar. And then the easiest thing, just piece of advice, go into the grocery store and eat from the perimeter of the grocery store. Do not even enter the center of the grocery store and you'll be off to a good start in terms of how to reduce your sugar intake. Everyone wants to ask me about alcohol. Can I drink alcohol? You know, I think we under, we don't really do a great job of gathering enough history on alcohol. So I want to just stress that it's important to take a really strong alcohol use history as a part of a diet history. I ask my patients, do you drink at least once a month? Do you drink at least once a week? It's a little different when you drink. How many drinks do you have to kind of data the amount that they're having on a drinking day? And then also quantify binge drinking. How often are you drinking more than four or five drinks on a drinking occasion? And you'll find that, and we've seen in some of the work that we've done, that alcohol, even modest consumption, contributes to liver fat. We know alcohol is a risk factor for liver cancer. You know, you can find studies that will show a benefit to modest alcohol drinking in terms of liver fat. But I think that they are generally cross-sectional in design, subject to residual confounding. And the bottom line is that alcohol is contributing. Your patients are definitely drinking more than you think they are. And you probably have not taken an adequate history. So we talk about alcohol and we, I really discourage my patients from drinking alcohol. But what you can do is you can drink coffee. So caffeine, particularly caffeinated coffee, may decrease liver fibrosis. Just make sure you're not getting a pumpkin spice latte with all of the yummy sugar and cream because that may defeat the purpose. So I will pass the controls back to Dr. Nordeen. Michelle, that was absolutely brilliant. Just what we needed. With these two fascinating talks telling us how much weight loss we need, also going through the patient's list of food and the degree that Dr. Long talked to her patients about in terms of the sugar and other component of the food. Now, my pleasure to move to the next kind of chapter of this talk. And I want to present Dr. Zach Henry. Dr. Henry is a transplant hepatologist in Virginia He founded the Weight Management Clinic to provide patients with nephro-access to multidisciplinary approach and lifestyle intervention. His clinic is unique. He works closely with endocrinologists, cardiologists and other specialties. And importantly, Dr. Henry is board certified in obesity medicine. So the next 15, 20 minutes, we'll see what Dr. Henry does in that special clinic. And then we're going to hear from Wayne about the patient's perspective and what do they want us, the hepatologist and pediatrician, and tell them what we're missing, telling them. With that, I'll pass it to Dr. Henry. I'm going to go over essentially what we do in our clinic here, which is a weight management clinic that I was very lucky to be able to put together with a cardiologist and endocrinologist here at UVA so that we could share resources for what I would say is a mutually beneficial goal, even though we're all coming at it from a different perspective. So I think the best place to start is really just to review, in my opinion, what every patient needs. And certainly I understand, and we'll go through this, and some people may have questions. A lot of this is resource intensive and that can be a challenge, but to really achieve weight loss, we have to be able to discuss not only dietary changes and exercise changes with patients, but also behavioral therapy. It's really important for patients who need to lose weight to be able to talk to a counselor, talk about motivation, talk about barriers, and really they're much more successful when they have that as part of their care. And so I think as hepatologists, where we all have to start when we first get that referral for NAFLD, or in many cases, honestly, for elevated liver enzymes that we quickly determine is related to NAFLD, is that we need to be able to give at least some basic guidance in clinic at that first visit to our patients, just basic diet and exercise recommendations. But I also think it's equally important to relate those recommendations back to their diagnosis and then have that discussion about what it means to have NAFLD and NASH, progression of fibrosis to cirrhosis, et cetera, because many patients just don't understand what that means. And I've had patients on all ends of the spectrum, some who come to me and think that they have liver failure because they have a diagnosis of liver disease, and others that think it's no big deal. And so it's really important for us to link those two things together for patients. And I don't think I need to go over this too much because Dr. Long just went through this very well, but I think with nutrition, if nothing else, if we can provide something like this, something like a one or two page document for patients, it's very helpful. And when I first see folks, many of them are in a pre-contemplative phase where they are not quite ready, they're still kind of digesting their diagnosis, and they're not ready to take that leap and really do high intensity lifestyle intervention. And so for most of those folks, giving them something like this, just as a broad overview of healthy diet changes can be good for them. And then when we discuss physical activity, I think it's really important to discuss this spectrum with patients. You know, I think most people, most patients rather kind of confuse exercise and physical activity for the same thing. And it's really more of a spectrum, right? We all know having a sedentary lifestyle is bad for multiple reasons. Getting up and moving every hour, adding just some basic walking throughout the day, those are all things that increase activity levels. But when we talk about exercise from a research perspective, these are dedicated exercise interventions on top of people's daily activities. And I think patients sometimes get confused about what this means. And we certainly don't wanna jump on people to start over here at 300 minutes of exercise per week. Most people are gonna need to start down here and slowly work through this until they're comfortable with that. But having that understanding upfront is very helpful for patients so that they know what to expect. And then, as I said before, behavioral therapy is a key component of this that I know many of us don't have access to from a resource perspective. But when we do, having a mental health professional work with patients is hugely beneficial. So to be a little more specific about diet, one of the keys I have found with weight loss is definitely one size does not fit all. What you will find with many different diet programs is that weight loss and even weight maintenance look very similar to this graph in this study comparing low-fat and low-carbohydrate diets. So meaning they both achieve the same amounts of weight loss and weight maintenance over time. And here, this is actually a more recent study called the Diet Fit Study, where the investigators were actually trying to find genetic predispositions to patients that may do better with a low-fat or a low-carbohydrate diet. And even when trying to manipulate those groups, you can see they're almost the exact same results for each patient. And this doesn't mean that those studies that suggest that certain metabolic parameters get better with specific diets are wrong. Certainly in low-carb diets, we tend to see more improvements in things like blood pressure, triglycerides, hemoglobin A1C, and even liver fat. But in the long run, when it comes to kind of sustaining weight loss, it really comes down to doing what patients can work with. And here, even in this older study, comparing kind of specific diets, Atkins, Weight Watchers, Zone, you can see there's really no statistical difference in weight loss or weight gain. And I think the importance of these slides is really that we have to be able to listen and talk to our patients and figure out where they're starting before we can kind of guide them to what may work for them. Because I've had some patients that do great on a low-carbohydrate diet, but then I've had other patients that don't really want to do that, but doing Weight Watchers and counting points is very easy for them and a good way for them to lose weight. And so a big part of this is really getting to know our patients and understanding what is or isn't gonna work for them. The same can be said for physical activity. Certainly, at the end of the day, something is definitely better than nothing. We know that exercise can improve hepatic steatosis. Maybe a signal that it can improve fibrosis, although that's not as certain. I think another important aspect of this, kind of like the diet, is that different kinds of exercise can be equally effective. So here's a study in patients with fatty liver disease, but there have been multiple studies in patients with diabetes, hypertension, just obesity, that suggest both aerobic training and resistance training, like weight training, are equally effective at weight loss and metabolic improvements. And some people are gonna be more ready to do aerobic exercise. Others may prefer to do resistance training. And I think when we start with folks, it's important to start with what they're comfortable with, get them doing something that they're comfortable with or in an ideal state, something that they enjoy, and then build on that over time. Because in the long run, we may want to include all aspects of exercise, both aerobic and resistance training, but trying to get our feet in the door in the beginning is really just understanding what patients can do and what they're willing to do. This graph is sometimes depressing when I talk to patients about it, but I also think this is equally important from a motivation perspective. So we know exercise can improve metabolic parameters, but to be totally honest, exercise just doesn't really affect weight loss that much. It's very good for weight maintenance, but one of the reasons we have to be upfront with patients about this is because I've had many people, you know, they go home, they get excited, you know, they're going to the gym, they come back, you know, two weeks, four weeks later, and their weight hasn't changed at all. And they just tell me they're gonna stop exercising because it's not making a difference, when in reality, their blood pressure's improved, their blood sugars are improved. You know, they'll even tell me physically, they feel better, they have more energy, but because the scale hasn't changed or they don't feel like the image in the mirror has changed, they wanna stop. And so I think being upfront about the advantages of exercise beyond weight loss is important to get people started down that path. And because it's so important for weight maintenance, it's something we really have to do from the beginning. And then just going back to this, we, you know, we may be starting down here, but I think we can all slowly kind of move our patients through this grid with this ultimate goal. We just don't want people trying to start here because this is also very discouraging. And if people try to start on this end, they're probably gonna end up having a joint or muscle injury. Behavioral therapy, which as I said before, in our country is often overlooked and not supported from a financial perspective, is equally as important. And in this study, they were actually comparing group counseling sessions versus individual. And you can see that actually, whether it was group or individual, pretty similar changes in weight, no matter what. And I put this in here because depending on where patients live, they may not actually have a choice. What's near them might be a group counseling session and not an individual counseling session, but we need to understand that both are effective and kind of whatever we can get our patients into is what's gonna be best for them. And this is a unique finding, at least that I thought, when it comes to counseling and high-intensity lifestyle intervention. Weighing every day is actually beneficial. It helps keep people focused. It helps keep them motivated. And as you can see from this graph, it helps with an increased amount of weight loss. I do wanna point out though, that this is in the setting of kind of ongoing counseling, multiple clinic visits, and high-intensity lifestyle therapy. I do discourage people from weighing every day if they're not actively working towards a weight loss program, because then they can get pretty discouraged by not seeing changes. But once we have people in that process of high-intensity lifestyle intervention, I think this is a good idea and something that we should really encourage our patients to do while we're working with them. And this actually shows that once patients lose weight, patients that do monitor their weight daily and continue to do counseling at least monthly, actually maintain more weight loss going out to one and a half years after reaching their native weight. So again, long-term maintenance therapy is just as important. So to get started with high-intensity lifestyle intervention, patients have to be motivated. From a motivational interviewing perspective, they have to have that change speak where they're sufficiently motivated, they're ready to do this. And in that scenario, seeing a patient every one and a half to two weeks for that first six months is highly effective. And that's what this study showed. Here's 16 sessions compared to 24 sessions in the first six months. They had pretty equivalent weight loss and weight maintenance. And because 16 is more convenient, the ultimate recommendation is actually somewhere between 14 to 16 sessions in the first six months. And for us, for patients with NAFLD, we want them to hit this 10% weight loss mark and you can see that people in this intense lifestyle intervention group almost 40% hit that mark, which is much higher than anything we've seen in any of our specific NAFLD studies. And this is another good reason to really push high-intensity lifestyle intervention when people are ready to make that change. This also shows that over time, kind of shifting that to a once a month or once every six weeks in-person or telephone encounter also helps maintain that weight loss for longer. So out to four years, they still maintain up to 5% of that total body weight loss. It's not as good as the original result, but it's much better than the control group. And so, although that first six months is very intense, continuing some kind of moderate intensity follow-up thereafter seems equally as important. So I think, you know, from where we start that initial clinic visit and the basic guidance, you know, option one and two are where as hepatologists we need to be able to to kind of push patients over the long run. So I think for many of us who maybe aren't in a large academic center where we have these multidisciplinary clinics, you know, option one is really what we have. So, you know, referring to a patient to a dietitian and then separately referring them for counseling or for physical therapy, which is a great way to get over some of those musculoskeletal complaints related to obesity, but also to transition them into, say, a gym program in the long run. You know, and where I, this is what I did for years and to be totally honest, the reason I then subsequently went and sought out and created this multidisciplinary clinic that we have is because I got frustrated from a resource perspective. Now since then, I have educated myself on the state of Virginia. So now even a patient who lives four hours away, I kind of have some maps of where dietitians are located, what counseling services are available, but I honestly can tell you too that took a long time to put together, but that kind of information can be invaluable for patients. And then ultimately, if you're fortunate enough to have your own multidisciplinary clinic or to be at a center where you have a medical bariatrics clinic in conjunction with a bariatric surgery clinic, they're going to be doing a lot of the same interventions of high-intensity lifestyle intervention with those patients, and so that's a good place to refer folks to get started. And so now I would like to turn this over to Wayne Eskridge, who is the founder and CEO of the Fatty Liver Foundation, and the Fatty Liver Foundation was kind of born out of, you know, Wayne's own travels through liver disease, but through that he realized that there was, you know, kind of a severe lack of patient education and educate reliable educational resources, and so he has worked tirelessly as a patient advocate through the Fatty Liver Foundation, and I'm going to let him take over to discuss the patient perspective. Well, I'm really honored to be here. It's unusual that I get to talk to this particular group. We deal in the foundation with the patients after you guys have seen them and sent them on, and so we see the difficulty that patients have in both the information they receive as well as their ability to follow whatever it was that you said to them, but a lot of this depends upon how the patient relates to what you tell them. From what you've heard in this seminar, you know, there's very difficult, it's very difficult to come up with good rules for people because the research is not really exciting to, it says, well, almost anything works and almost nothing works. If you really do this, you'll have some success, but a lot of people don't. You know, the diet industry is a 70 billion dollar a year failure because everybody yo-yos back up. So the thing that we want to stress is that you have, at that moment when you're dealing with people, if they had a diagnosis, you have a very teachable moment, and the things that you pass on to them at that time have a potentially profound effect, but it is often, far too often, not presented in a really persuasive way by many people in the medical profession. This slide that you see there, it says half of liver specialists feel very confident discussing lifestyle modification. I don't think it's that high, really. You know, you guys are all pressed for time. Almost nobody in the country has the kind of resource that Dr. Henry has. You all struggle with time, you struggle with resources. It's most common that people get the advice to lose some weight and a little bit of guidance, and they don't come away understanding the real risks that they have, and I think that's one of the biggest problems of people hearing things like, well, you know, fatty liver's not a big deal. It's everywhere, you know. We talk about fatty liver, but you know, we frequently have this, well, it's not a huge thing. Until you get to cirrhosis, people don't connect, and I've put this bit up here from Paul Angula, did some work on the hazard ratio of this, and something that I think that's important is to understand, for the patient's perspective, that according to this study, for example, a fibrosis stage 1 is more dangerous than diabetes. A stage 2 is more dangerous than smoking, and we care very much about diabetes and smoking, but we don't impart that same kind of concern to patients when we talk to them about NASH. So my counsel is to make sure that people appreciate that the risk of NASH and the possible consequences are real, and they need to take it very seriously. So, Dr. Henry. So, you can read all that, but let me talk about, in general, how we as the Fatty Liver Foundation approach the diet, because when it's all said and done, the research that you have, you know, we say, well, it's inconclusive. We don't have enough good trials. We don't have enough good evidence, but in reality, a person still has to go out in the world and make a real diet out of something, and a very simple idea that we use is don't eat anything white. You know, don't eat sugar, salt, white flour, potatoes, you know, that just is a mental image, because first thing that we want to do is eliminate as much sugar as possible. We want to get off of the salt, the high, very high salt diet that we have in the American food system, because we have a lot of problems, and with liver disease, and with ascites, and all of the complications that go with balancing the salt. You saw some evidence that saturated fats are not as good for you as unsaturated fats, so our approach is to limit saturated fats and increase, deliberately, the unsaturated fats, and we do that through extra virgin olive oil. So, we recommend people use plenty of extra virgin olive oil, and we recommend that they increase their omega-3s and decrease their omega-6s, so we talk to them about fatty fish, and we talk about seed oils, and to, you know, try and balance those things, because those balances are important. We basically talk about not buying anything in a box. It's just, if it's in a box, it's processed, and probably the fiber is broken down, and it's not as good for you, and it's got stuff in it that you don't need. So, those are the kind of simple rules that we talk about, and generally speaking, people need those kind of broad understandings, because what they want to do is to talk about their diet as they live it, and you can't know what their diet really is and how they live, so you need to provide to them a concept of the kinds of things that they need to be increasing in their general food, and the things that they need to be decreasing, and those are, you know, fairly broad. When you talk about saturated fats, we talk about the differences between saturated fats. We point out that the beef fat, tallow, is more inflammatory than chicken fat, just as an example, and so if you're worried about inflammation in your liver, you're better off having chicken than beef. Both provide good protein, but, you know, the chicken is better for you. Plant-based diets are better for you, because, you know, they don't have some of the saturated fat issues, and you get a lot of fiber and a lot of vitamins, so those are the kinds of conversations that we lean to in order to give people a broad construct in terms of thinking about it, because we can't know what their day-to-day diet really is, but if we can get them to think about the structure of the general foods, then they have a chance to build on that over time, and, you know, I can say that your work on the effect of weight loss is really fantastic. I lost 30% of my weight, and I went from a fiber scan of 21.5 to a 9.6 today. Congratulations on your weight loss. This is your role model for our other patients, and thank you for all the speakers for this great talk or great talks. I'm going to go to the Q&A session really quick. There are actually really good questions in the Q&A, so I think Doug Levine, Amy Schneider, they asked a very important question about the fructose, and I get this question also from my patients, the fructose in the fruit, and Michelle, why you don't take that question? Sorry to pick on you. You spoke about this topic. What do you feel about the fructose overall, and when they ask you about the fruit in particular, what do you answer your patients? Yeah, that's a great question. You know, when you eat fructose in a fruit, you're also getting other vitamins. You're getting fiber. It's not going to be this rush of sugar to your liver like it would be if you were to drink it in a form of a beverage, sugar-sweetened beverage, so that part is certainly different. You know, I think that there are numerous studies to show that fruit is associated with weight loss, fruit consumption, but are all fruits the same? Probably not. You know, I think that when I'm trying to talk to my patients who are eating ice creams and other things that are clearly not good and clearly have a lot of added sugar, fruit is a great substitute as a stepping stone. If we're not making headway when they switch to fruit, then we may consider decreasing fruit, but overall, fruit is associated with weight loss in general, and I think because you're getting all that healthy fiber and other things, the dose of fructose is less, so I don't really worry about it. It's very different than eating a Snicker bar. Another very important question about the artificial sweeteners as well as the diet soda. Do you or you do not recommend that to your patients? Maybe Michelle and Zach can take that on. You know, the issue with the diet soda is that you often get that insulin spike as well, so even though it's a diet soda, it still may not be healthy for you, and it may ultimately have a risk for worsening insulin resistance. I know there are some questions about lean Apple D or insulin resistance tends to be a major issue, so I do not recommend diet soda consumption. Zach, do you feel the same? Yeah, I agree. I think when we talk a lot about sugar in the diet, and a lot of our patients have the overlap with diabetes, so they think a lot about blood sugar. They don't usually think about their blood insulin levels, and insulin in these patients really disrupts fat metabolism. It leads to a negative inflammatory cycle that makes just all of metabolic syndrome worse, including Apple D, and so I try to get people to avoid it as much as possible. Right. This is an important question. Let me ask actually Manuel and Zach about the lean patients, and should they lose weight? They should not. Exercise is good for them, because you alluded on that, so let's see what the Spanish people do for people in Spain that they are lean. Professor Manuel Romero-Gomez. Yes, the key point for this question is if it's a true lean patient, and we need to be absolutely confident the patient is lean, because as you know, BMI is not the best manner to know if the patient is overweight or obese, no? We need to exclude visceral fat, and if the patient is in spite of apparently to be lean, could not be. This is the first point. The second one is when we are planning what can we do with this patient, it's completely different if the patient is a true lean or not. If not, we can start with a lifestyle intervention, and if the patient is a true lean, we need to look for the main pathophysiological mechanism we can try to address, mainly looking for secondary cause. Zach. Yeah, yeah I know, the lean patients are always tough for me. I think a lot of times I look more at their body shape or body habitus, you know, it's that central adiposity that is really concerning, and even patients who have, you know, a BMI of 23 or 24, but carry a lot of their weight in the middle, you know, exercise but still healthier diet can lead to, I mean, a more modest amount of weight loss, but they may also preferentially lose weight in that central zone, which metabolically is beneficial for them. And so, you know, I would say I approach exercise pretty much the same with everybody as far as trying to evaluate what they can do, and whether you're lean, overweight, obese, I'm gonna push that pretty hard. I think the dietary changes in patients who are lean are the ones where I may focus a little more on macronutrients and less on just weight loss in general. You know, when I have obese, and unfortunately nowadays, more and more commonly morbidly obese patients, I'm kind of looking for any dietary change just to get some weight loss, but I think that lean population is one where we can really maybe push more of the macronutrient changes for them. Great. So there are a couple of questions on keto diet. I don't think we have enough data yet on keto diet on NAFLD, and there's a question about supplement current at the current team. I think it's a very interesting supplement, but we still need more data. An important question is, and thanks to Wayne pointing out all these difficulties that the patient go through, and how much resources we have in clinics. And the question here is, how many hepatologists they have a nutritionist in their clinic? I can tell you it's low, but Zach maybe has asked around with his extensive work. Zach, how many you think they have a nutritionist, and how can we overcome the obstacle of not having a nutritionist in fatty liver clinics? Yeah, I think so what I've learned over time, so that was kind of my rule number one when I started my clinic. The main thing I wanted, I actually originally just asked for a dietician. That was all I wanted was somebody who could work with me in clinic, and I learned a lot about how dieticians bill when they see patients and how insurance covers it, which is almost not at all. If your patient has type 2 diabetes, they might cover three visits with a dietician and then nothing after that. Unfortunately, what I've learned is for a dietician to be truly effective, they kind of have to be embedded in your clinic or in a clinic where you're paying for their services in a sense, so they're not really billing, but they're an adjunct to your team. I still frequent dietary clinics in other parts of the state where I have patients who are far away, and they work wonderfully well, and most of them will work with patients to try to make it affordable, but seeing a dietician can be as much as a hundred plus dollars out of pocket for a patient, and so that's definitely a very difficult thing, and I'm not to be a pessimist, but I had to petition for a while, you know, my division chief before I was able to kind of work that out. Oh, congratulations on getting your setting done. I was lucky. So Wayne, we need people like you to change that with a disease prevalence of 30% and not covering dietician services in our clinics. Anyone has more questions, please feel free to email any of us. Again, on behalf of the ASLD and the NAFL Special Interest Group Steering Committee, we could not have been happier than these talks, brilliant talks today, went through details. I think it will change a lot of practices, people learned a lot. Thank you very much, and looking forward to the next webinar. Thank you very much. Thanks, everyone.

dietary recommendations

NAFLD

weight loss

liver damage

Mediterranean diet

metabolic dysfunction

exercise

patient education

lifestyle changes