Series Overview
Join our host, Dr. Amreen Dinani, as we discuss an often undetected liver disease affecting up to 25% of the world’s population: nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH). Each episode, Dr. Dinani is joined by hepatologists from across the United States to discuss various components of the NASH care continuum, including early identification, diagnostics, existing and emerging treatments, and the patient care journey. Whether you’re a patient, hepatologist, primary care provider, endocrinologist, or payer, we hope you can join us and learn something new!
Episode 3 - Existing and Emerging Treatments
In Episode #3, Dr. Dinani and Dr. Sussman, an Associate Professor of Surgery at the Baylor College of Medicine and Medical Director of Project ECHO at Baylor St. Luke’s Medical Center, discuss existing and emerging treatments, the importance of patient education, and the role providers play in influencing and encouraging sustainable lifestyle changes. Listeners will learn more about:
Current strategies for managing NAFLD/NASH
Opportunities and challenges associated with emerging treatment options
Key considerations for primary care providers
Listen on Soundcloud, Apple Podcasts, Spotify, or wherever you get your podcasts.
Transcript
DR. DINANI: Hello and welcome back. You are listening to Episode 3 of our podcast miniseries covering an often undetected liver disease affecting nearly a quarter of the world’s population: nonalcoholic fatty liver disease, which we’ll refer to as “NAFLD.” The more aggressive form of the disease is called nonalcoholic steatohepatitis which we’ll refer to as “NASH.” I’m your host Dr. Amreen Dinani. I’m a hepatologist specializing in liver disease at the Icahn School of Medicine at Mount Sinai Hospital in New York City. Today we have the pleasure of speaking with Dr. Norman Sussman, an Associate Professor of Surgery at Baylor College of Medicine and the Medical Director of Project ECHO at Baylor St. Luke’s Medical Center. Dr. Sussman, thanks so much for joining us.
DR. SUSSMAN: Thanks, Dr. Dinani. It’s very nice to be here.
DR. DINANI: So, I thought we’d start off by letting you know that we’ve done two podcast series like this before, where we really just talked about the burden of NAFLD and NASH and the fact that it’s a growing issue and problem, both in the United States and worldwide. We touched on the implications of having NAFLD. We also talked a little bit about simple diagnostic tests and how we can risk stratify someone with NASH, so what we’re really hoping to achieve today from talking to you is — once we diagnose people with NAFLD and NASH, what treatment options do people have? Because as you know this is a big, messy disease, and we really haven’t made much headway in a systematic approach to this disease. So, to start off if you don’t mind, would you tell me a little bit about, for instance, if you have any initiatives that you’ve started already? It would be great to hear what you already do.
DR. SUSSMAN: Thanks. Baylor College of Medicine is in Houston, Texas. Texas has a very high prevalence of obesity. Houston has several times been ranked in the top #1 or #2 for average body mass index (BMI). It’s a very common problem that we see. Baylor College of Medicine covers three hospitals in Houston: a county hospital called Ben Taub Hospital, the VA Healthcare System, and the private hospital called Baylor St. Luke’s Medical Center. The faculty generally works at only one of those, but we speak to each other very frequently and have developed a combined program where we try to collect the same data on patients at all three centers so that we get a broad view of population health. That is, what do the people in the Harris County Health System experience, what do people at the VA experience, and what do people at the more private environment experience? We’re a little bit slanted towards advanced liver disease because we have a liver transplant program, and so the university hospital tends to see more of the very advanced patients, but we remain very interested in the early stages of fatty liver disease, or NAFLD, and saying can we move this whole process upstream and get patients to understand that the choices they make now may prevent the end stage liver disease that they may see as they get older.
DR. DINANI: That’s a perfect overview of your healthcare system, and you really emphasized a key point that depending on where you see these patients, not just within the country but also in different healthcare models, you will see a different prevalence of disease but also severity of disease. It will be very interesting to hear more about what you get out of some of the data that you’re collecting. So, jumping to what we actually do with people with NAFLD or NASH – once you’ve actually identified someone at-risk for NAFLD, or confirmed the diagnosis of NASH, and as you know we do that now with a liver biopsy as of today the standard is really to do a liver biopsy – what is your approach to treating NAFLD and specifically NASH as well?
[4:07]
DR. SUSSMAN: The key elements are: Are we making the right diagnosis, does this patient have NAFLD or NASH, and are they at risk or is it possible they have another coexisting condition? The two that really come to mind are: 1) are they drinking alcohol, so do they have a combination on nonalcoholic and alcoholic fatty liver disease, and 2) do they have something in the background like a chronic hepatitis or other condition? First, we try to separate those out and say, “how convinced am I that this is fatty liver disease.” When patients come in for their first visit, many times they come in with a full evaluation from their referring doctor, so if looks like this is the case, we discuss it at the beginning – here are changes you can make to your lifestyle, including: what is healthy food, what is unhealthy food, what is physical activity, what is too much, what is too little? I emphasize that there’s no one diet that works, but they need to find something that is healthier than the diet they’re currently using. I give them a period of time, somewhere between 6-12 weeks, to show that they can change that. If they come back and their liver tests are much better, and they tell me, “I’m feeling better – all these symptoms I was having are better,” then I feel we’re on the right track, and I’m justified in not doing a liver biopsy. If their liver tests don’t improve despite a lifestyle change or if they just failed to do the lifestyle change, then I think we’re obliged to do the biopsy because you have to say, “I have to make sure this is actually the correct disease… I’m actually treating what I think I’m treating, and I’m not being misled by some other diagnosis that could be very important to your survival and to your long-term health.”
DR. DINANI: So, you mentioned diet and you mentioned exercise. We live in a country where there’s lots of different ethnic backgrounds, and one of the things that I find when I see people with nonalcoholic fatty liver disease is by the time they see me, they’ve tried every diet that’s out there. Typically, people just want to know what to eat, so an approach that I found very effective, and I think it’s a very similar approach to yours, is learning what the person or the individual eats because if you’re dealing with someone from a particular ethnic background, you cannot just counsel them on cutting out the bread, the pasta, and the rice if those are things that they typically eat. I find that approach and having a personalized approach to every patient, irrespective of disease burden or severity of NASH, does make a big, huge difference to sustainability and effectiveness of the recommendations we’re making. The other thing you talked about was exercise. Is there are a particular exercise that you recommend, or do you just tell them that they need to move? Is there a goal that you’re asking them to hit?
DR. SUSSMAN: First of all, I think what you said about ethnic background is really important. I always ask them what they’re consuming, and I specifically focus on – do they drink sweetened drinks? In this part of the country, sweet tea is a popular drink. Are they drinking sodas? Are they drinking fruit juice? I try to show them where sugar is. I spend quite a bit of time explaining that this is what I mean by sugar. These are simple carbohydrates. These are complex carbohydrates. This is where you may be getting them, and I try to focus them on where they could cut this. How could you reduce this? I’m not trying to get them to make ridiculous changes. I really emphasize that I need you to make changes that you can live with for your whole life. In terms of physical activity, many people do so little that it’s sort of shocking. I ask them to just start out very simply. I tell them that I’d like them to do two kinds of activity. Number one, is I really want you to do some kind of resistance training, and depending on the patient that could be using light or moderate weights, or it could be using rubber bands. If I’m worried that they may drop things, I try to use something where I don’t think they’ll hurt themselves, and I say this is a long process. Build it up. Start walking five minutes a day. Instead of parking at the front of the building, park a little farther away, and walk the extra 500 yards. I try to get them to take really small steps, and I tell them, “you will recognize each achievement yourself.” When they come back I ask them about them, so I try to celebrate their victories when they come back. I’m always trying to give them positive reinforcement.
DR. DINANI: That’s great. Another aspect of lifestyle that we know is very effective for treatment of NAFLD is weight loss. In addition to adopting a sustainable, healthy diet and getting some form of physical activity to change your metabolism and how you deal with glucose control specifically, how do you avoid giving the blanket statement of “you need to lose some weight?” I’ve found that talking to patients, they find that to be very discouraging, ineffective, unless actually given some tangible goals. How do you advise people on weight loss, and could you tell us a little bit about the impact of weight loss on NAFLD?
[9:39]
DR. SUSSMAN: I can’t even enumerate the number of people who say, “my doctor told me to lose weight,” and I say, “did your doctor say how you would do that,” and they say no. I said, I’m going to give you some very specific instructions, starting out with telling me what you eat, and I’ll say here are ways you can cut these out. I focus very much on the simple sugars but also depending on the patient and their ethnic background some of their complex carbohydrates. As an example, if I have an Asian patient who lives largely on rice, I have to say, “how do I reduce the amount of rice.” Saying “don’t eat rice any longer” is not going to work, so I have to say “can you cut your rice with quinoa, or can you add vegetables” so there is less rice and you’re getting a slightly smaller carbohydrate load. I really try to taper it to the individual, and I try to give them specific examples. I ask them – what does this have in it? Tell me about this drink. Is grape juice health? Is orange juice healthy? Just so that they really start to think about the food they eat. I think a lot of people just eat without really thinking. That’s one of the problems. In terms of the weight loss goals, depending on where they are, what they’ve done before, and how diligently they’ve done it before, I would say generally when people have not been on a diet before and they come in, if they pay attention to the diet, it’s not unreasonable for them to lose 10-12 pounds in that 12 week period. That first weight loss is actually the easiest. I always tell them, “don’t get discouraged if you hit a ceiling because there will be a temporary break somewhere where you will stop losing weight. Don’t let that bother you. Stay healthy because you’ll eventually get through that.”
[11:29]
DR. DINANI: That’s great advice in terms of lifestyle – how do you achieve sustainable weight loss goals – and in particular, I like the fact that you comment and stress on the fact that sweetened beverages (e.g. high fructose corn syrup) especially can be detrimental to fatty liver disease but also are very easy ways to cut calories. I wanted to switch to some things that are discussed in some of our society guidelines in terms of treatments, and common scenarios that I do see in clinics. The first one of the utility of Vitamin E. I have many patients that come into clinic that have already started Vitamin E. What are your thoughts on Vitamin E? Do you have any thoughts or advice on how to use this or not to use this?
DR. SUSSMAN: I think that it’s a controversial question. The study that demonstrated utility of Vitamin E was a very carefully done study by a very well-respected group of investigators. They did show a benefit. Later, there was some criticisms about maybe there’s a negative side to Vitamin E, and maybe you would end up balancing the good with the bad. I don’t typically give Vitamin E, although I’m well aware of that information. The reason is that I worry we’re very medication oriented in the United States, and perhaps in the world, and people want a pill and once they get that, they say “ this is no longer my responsibility… the doctor is going to give me a medication that is going to solve this problem.” So, I generally do not use Vitamin E, especially early on. If they come on Vitamin E, I say “you can continue to take it.” Frequently, they’re not taking the natural form. They’re taking the synthetic that is probably not as helpful as the drug in the study, it was called the PIVENS trial, which was a natural Vitamin E. The synthetic one may not be quite as effective, so I tell them it’s possible you may get some benefit, you may not get some benefit, but I really try to focus on their general health and less on tablets. Although there are actually some medications that I think may help.
DR. DINANI: That’s great. You know you mentioned about Vitamin E that all forms of Vitamin E are not the same, and of course the one that was looked at in the PIVENS trial is quite different in the natural form than what’s available in drug stores or health stores. The other thing about Vitamin E is there’s some people who just respond better to Vitamin E than others in terms of how they help with inflammation or oxidative stress, which is a huge pathway in the development of this disease. It also doesn’t work the same way in every individual. You mentioned that there are medicine that you would be in favor of. What types of medicine might those be?
DR. SUSSMAN: My second favorite topic – what medications can we use? I start out by looking at what medications is the patient taking that might actually be making it difficult for them to lose weight. Among those, one of them is beta blockers, which I see used less, but I think it slows metabolism down and may make it harder for people to lose weight. The one in particular is insulin. I really look at whether they’re chasing a high blood sugar with insulin, as opposed to managing – take a sugar and use the insulin to bring the blood sugar down. If they didn’t take the sugar in the first place, they might not need insulin. Insulin is a major problem with weight gain. Then, some of the newer medications for diabetes actually do help with weight loss, and one of them is actually approved for weight loss in itself. Those really may help patients get their weight down and control their blood sugar. I have a lot more confidence in those medications, and as we look to the future and what medications we’ll be using for fatty liver, I think that medications that have the dual effect of improving blood sugar and helping with weight loss will end up being the most effective.
[15:45]
DR. DINANI: Thank you for that. What are your thoughts on statin therapy? A common scenario that I see in the clinic is I see patients who have been referred to me with slightly elevated liver enzymes, so an ALT or AST, and their primary care physician, or sometimes even their subspecialists that are looking after them, have stopped their statins. What are your thoughts or advice on statin therapy and fatty liver disease?
DR. SUSSMAN: Yeah, I think we’re seeing the same patients because we have that same problem. Frequently, the primary care doctor has stopped their statin. I tell them I think that’s a big mistake. Statins really actually help people with liver disease. They have an anti-inflammatory effect. People generally do better with them. A very, very small number of people do have an adverse reaction to them where their liver tests go up, but in general I consider them very safe. I encourage them to speak to their primary care provider, or sometimes I’ll even call them and say, “I think you should put the patient back on the statin.” I always put that in my note to say statins generally are better for these patients. If they need a statin, it’s a good choice.
DR. DINANI: Great. Thank you for that. I’m pro-statins as well, so not only advising the patient, but also reaching back to the primary care physician to make sure they restart their statin therapy because not only does it have cardiovascular benefits, which is really important in this patient population. If you don’t have advanced liver disease from fatty liver disease, some of the leading causes of mortality are related to cardiovascular mortality. I try to really emphasize that, but also, there is some evidence to suggest that maybe it really helps with the scarring and the fibrosis that we see with this disease.
DR. SUSSMAN: I agree with that.
DR. DINANI: You mentioned that at present we don’t have any medical therapies that are specifically targeted toward NAFLD or NASH. We do have some effective medical options to treat some of the comorbidities, so some diabetes medications, as you alluded to, and weight loss medications that we could use and be proactive with statin therapy. There’s a lot of molecular targets out there being investigated right now in Phase 2 and Phase 3 trials. It’s a common question: do you think there’s going to be one pill or one medicine that’s going to work for everyone with fatty liver disease once approved? Do you think it’s going to be a combination of pills? Do you think these medicines that are going to be approved are going to target the entire spectrum of NAFLD? Any insight into what you think might happen with drug development?
DR. SUSSMAN: I think that some very smart and diligent people are working on this, and a number of targets that look extremely promising are being investigated. But, a lot of the studies that looked promising at the beginning when the larger studies were done had very small or no effect, in other words, the placebo affect was about the same as the drug effect. So, it’s very disappointing, but I think we’re going to see that for awhile. We do expect one drug on the market that showed reduced fibrosis, reduced scarring, and that was quite a surprise and very exciting. It’s not a huge effect, and it didn’t affect everyone. A percentage of patients seemed to get better, some didn’t, and I think that tells us that there are going to be different type of people with different types of fatty liver disease. We may have to refine our thinking and say that this kind of drug works on this kind of patient. Whether we’ll identify those molecular targets ahead of time and say, “this will be the drug that will work for this kind of patient,” or whether it’s going to be trial and error where I say, “I’m going to try this for 6-months and see if these parameters get better… and if they do we’re going to continue.” The cost of drug development means that those drugs are probably going to be very expensive, so whether anyone will actually pay for them in the long run I think is going to be a tricky question because the more effective they are, the better chance that people will pay for them. Then, I think that all the studies have shown that people who lose weight do better than anyone else. So, I think that drugs that affect weight loss – if it includes a drug that helps the patient lose weight, those I think are going to be the most effective combination.
[20:06]
DR. DINANI: Great. Currently, some of the work you do is you’re the Medical Director at Project ECHO at the Baylor Healthcare System, and I know a big part of that is interaction and education of primary care physicians. Have you used that model, or are using the ECHO model to education primary care physicians for NAFLD or incorporated that into your program?
DR. SUSSMAN: Yes, I have. So, we have a dedicated group of primary care providers, usually in community clinics, that deal with generally under-resourced patients who really rely on them for all aspects for their healthcare. Some of these are really outstanding providers. They’re advanced practice providers and physicians. Honestly, it’s a pleasure working with them. They face this problem all the time. We’ve had a number of discussions, and I’ve given several lectures on how I see this and how my view of fatty liver, the drivers for it, the interventions that make a difference… I’ve told them about the drugs that are currently in study, but I’ve advised them that we’re not going to see any of them soon. For that particular population, they’re probably not going to be that relevant because many of those patients don’t have the kind of insurance that’s going to allow them to get those kinds of medications. For people who do not have the resources, we really need a broad-based, simplified plan that says – here’s how you can get healthy, and here’s how you solve this NAFLD problem – it’s simply good health. If I could say one other thing – I try to point out to people that mentioning someone’s weight can be very tricky, and so it requires a really nonjudgmental approach, similar to what we use for alcohol where you say, “I’m not really judging you. This isn’t about how you look. This is really how your body works, and I can help you make your body work better. You will feel better, and your complication rate will be much lower if you can take these steps.”
DR. DINANI: Thank you, Dr. Sussman. Any last thoughts in terms of treatment or approach to the patients with NAFLD or NASH that you have for the audience?
DR. SUSSMAN: I try to convey to the patients how passionate I am about this, and how helping them get healthy is a real goal.
DR. DINANI: I hear it.
DR. SUSSMAN: It’s not about writing another prescription or doing another operation. They’re health is very important to me and to my partners. We want stay engaged with them and help them reach this goal. You and I go to a lot of meeting where people say, “oh everyone knows no one goes on a diet.” That isn’t my experience. I think if you spend the time, and you say here’s why I’m doing this, and this is going to be my job and this is going to be your job, then I think we have a chance of succeeding. I wouldn’t say that this works on every patient. There are patients that have not heard the message, and they’re a difficult problem. For them, I try to get them to a diabetes doctor or someone who can get them the medication, or I’ve even tried some appetite suppressants on those patients. It’s really – that’s a big of a failure because I feel I have not convinced them that their health is important to themselves and to me.
DR. DINANI: Yeah, you know you reiterate something that I echo and completely agree with. Patients really want to feel like you are committed to them because as you know, by the time they see us they’ve already heard about “go lose some weight… you’re overweight… you’re obese… you need to work on your diabetes.” They’ve already heard all of those things. One approach that I’ve found effective is once you start putting the liver into the mix, as in the liver could be an organ that could be affected by all these medical comorbidities such as type two diabetes, high blood pressure, and even things like sleep apnea, it does bring the disease to a different light in the patient’s mind. But, the other thing that I’ve found very effective is I actually tell patients to send me about a week to two weeks of a food diary. I physically go through it with them in ways that they can cut out unnecessary calories, for instance, if they’re drinking their calories, and I think that kind of commitment makes a big difference. The majority of the time, I think that if you connect at that level with a patient it makes a big difference, and one of the things to reinforce at every visit, I think, is addressing effective polypharmacy and addressing the whole issue with alcohol. Another aspect that we didn’t touch on is smoking. Smoking, just in general, can affect the liver with liver fibrosis, so working very actively with smoking cessation programs, support groups to help these patients through. I really think that personal commitment makes a big difference to this patient population because you’re right – it’s lifestyle. If you don’t change behavior, I can keep throwing things at you, I can keep writing prescriptions, but I’m really not changing your behavior that is driving some of this disease.
[25:32]
DR. SUSSMAN: The other thing is that no matter how small an improvement they’ve made, I always celebrate those improvements. I never say, “I wanted you to lose 10 pounds, and you only lost 5.”
DR. DINANI: Yeah, every bit matters.
DR. SUSSMAN: Exactly.
DR. DINANI: Every bit matters. If you don’t have any additional thoughts, I think we will conclude our session. I want to thank you for really joining us today and providing us with some insight into how you manage this growing disease that we’re seeing in the United States and worldwide. Just a reminder, this is part three of our podcast miniseries to increase education and awareness relating to NAFLD and NASH. Please join us next time to hear a NASH patient’s perspective. This podcast series was developed by NASHNET, a global center of excellence network, dedicated to improving NASH care delivery. Thank you again.