Crystal Ball Tells Us The Most Important Stories Of Autumn – Ep 27

Episode 27 Title and Panelists
The Surfers discuss four issues that are likely to affect how our thinking about NASH diagnosis, education, and treatment might evolve over the next three months.

Browse Our NASH and COVID-19 Coverage
Naim Alkhouri joins the Surfers to discuss some key NASH-related questions. The four key sections address upcoming clinical trials, steps forward in patient advocacy, the UK NCD report and need for patient education, and the pervasive impact of COVID-19 on how we think and talk about liver disease. Always lively, always provocative, and occasionally humorous, this episode is worth a long listen.

Roger Green: For everyone with an interest in NASH, or more broadly, fatty liver disease, surf’s up because episode 27 of Surfing the NASH Tsunami starts now. I’m coming to you this week from Corpus Christi, Texas, where the tropical storm Beta threatened to dump ten to twelve inches of rain and knock out power, before heading on a more northerly course over the weekend.

Roger Green: I had this fantasy where I was going to have to call Louise and Donna first thing this morning and asked which one of them wanted to emcee because I was powerless, but happily, that didn’t turn out. For those who haven’t been here, the coastal bend area of Texas has great beaches and laid back people and the Texas state aquarium, which is the perfect place to take your grandchild, complete with splash park, which we use for shooting low pressure water cannons at one another for five or ten minutes.

Roger Green: As I mentioned last week, this is our first episode of autumn. Today, we’re going to do something we did in June and we’re going to continue going forward. The first episode of every season will be a crystal ball look, three months ahead. Unfortunately, the summer episode, was eclipsed when the FDA announced their complete response letter for Intercept, two days after we dropped an episode saying that Intercept’s launch would be the big event of summer. This time, let’s hope for no surprises.

Roger Green: Here’s today’s big news. Steven is missing in action on a scheduled episode for the first time since we launched the podcast. For extra credit, do any of you remember the other one he missed and the reason why? Luckily for us, our good friend, Naim Alkhouri, is available to join Donna, Louise, and me. So, this should provide plenty of time to explore our four predictions.

Roger Green: I want to thank you. Last week’s episode had the biggest first day uptake of any episode, except the ILC episodes and the Intercept CRL letter we just talked about. Thanks for your continued enthusiasm. Now, I just want to figure out how we can get you guys to actually talk to us on bulletin board and discussion groups. We keep posting questions, nobody answers. It would really be great for someone to come in this week because we’re going to start making decisions on our AASLD coverage next week. And that’s the discussion group question we have right now.

Roger Green: Please ask questions. If you do, I’ll set up a personal phone call for us to discuss anything else you wish. If you don’t want to talk with me, I’ll see if anybody else is available. Finally, in terms of music, Naim and I haven’t discussed this, but I’m hoping to use another selection for the music that he sent us back a couple of months ago to escort us out of this week’s episode. People really praised it at the time. I don’t see why not now. So, with that, let’s go on to the podcast, starting with our icebreaker, which this week will be a professional highlight.

Donna Cryer: First of all, your podcasts would never be the same if you turned it over to a patient and a nurse together when you got it back. And I think that’s a good thing, but maybe we’ll see that in the future, as you continue your travels during a pandemic and a global climate change transformation. Professionally, for the Global Liver Institute, we have had continuing success with our relationship with the Centers for Disease Control and Prevention across the various divisions and their inclusion of a specific language for NAFLD and NASH, started first with a change in the diabetes education.

Donna Cryer: So, I’m very excited to what is gearing up towards a four CDC division panel that we’ll be able to do on liver health, that we’ve never been able to do before. So, I’m really excited about that.

Louise Campbell: We’ve been doing some trial scanning last week and it was just great to have people out and about, being safe, and trying to get access to diagnostics, which was a really nice thing to see. And each of the days we did was some really nice experience.

Roger Green: Naim?

Naim Alkhouri: I’m happy that we recently published a paper in hepatology about how to maintain the integrity of NASH clinical trials during the COVID epidemic with my co-authors, Doctors Anita Kohli, Rohit Loomba and Steven Harrison. I hope this will serve as a guide to optimize the conduct of these trials during COVID. And then, I’ve been working on my Twitter presence also, and I’m happy to report that I doubled the number of followers I have over the past two weeks. So, if anyone is there and listening, follow me @alkhourinaim on Twitter. I regularly post about liver related topics on my Twitter account.

Roger Green: That’s fantastic, Naim, and in some ways, it’s not so different from what I was going to say, which is that we’ve had a tremendous upswing in the number of HEP Dynamics followers and Surfing NASH subscribers in the last month. I think we probably increased that number by better than 50% from what it was. We’re getting close to 300 now, and I’m going to start a program of reaching out once a week or twice a week to people for fifteen minutes to half an hour just to call and talk about what you do within the NASH community and your interest in the podcast and what we can do to serve you better.

Roger Green: I’m hoping I’m in the middle of proving that I can go anywhere on the road I need to do a podcast. So, if this one goes well in terms of sound quality and all that, then all good.

Roger Green: Today is going to be a simple format. Each of us prepared in advance to talk a little bit about one specific item of interest that will be happening during the third quarter.

Roger Green: What we’re going to do is one surfer is going to discuss the topic, then the rest follow up. We’ll also ask questions. And then, we’ll go on to the second surfer and repeat the process, and then the third, and then the fourth. And if we have any time left, we’ll try to tie it together with a bow. And if not, someone will make an amazingly profound and pithy closing statement, Louise and Donna, both being famous for that. And then, we will go on from there to wrap up. Naim, why don’t you get us started, please.

Naim Alkhouri: Sure. Although 2020 has been a difficult year for all of us, we actually had a few positive developments in the NASH drug development space. I think over the next few months, especially at the AASLD Liver Meeting we will have several presentations with new therapeutic agents. I just wanted to summarize some of the promising results that we learned about recently.

Naim Alkhouri: First, I want to start with the Akero program. They have an FGF-21 agonist called the Efruxifermin. It used to be called the Akero 001. And they had a press release showing very promising results. Initially, they randomized patients to placebo or three doses of the FGF-21 agonist. And they showed that, according to MRI-PDFF, there was significant reduction in liver fat fraction.

Naim Alkhouri: And then, in patients that met that threshold of 30% relative fat fraction reduction from baseline on MRI, they actually did the liver biopsy and they showed significant improvement in liver fibrosis. 48% had improvement by one stage, 28% had improvement by two stages. And this is a very short period of time, only sixteen weeks. And there was also NASH resolution, weight loss with the higher doses, and improvement in lipid profile. So, I do believe that this is a promising program, and I look forward to learning more about it at the upcoming Liver Meeting.

Naim Alkhouri: The other exciting program we have in NASH is with Inventiva and their drug, Lanifibranor. This is a pan-PPAR agonist, PPAR alpha, delta and gamma. And this was a longer trial, it was twenty-four weeks. They had a lower dose, 800 milligrams daily, higher dose, 1200 milligrams versus placebo. And the results, based on biopsy, were very impressive because they met both primary endpoints that constitute the FDA regulatory pathway for drug approval. They met NASH resolution with no worsening in fibrosis, and also improvement in fibrosis by one stage with no worsening in NASH. This is very impressive. I think the drug has a positive effect on metabolic syndrome components, except for weight gain. And there was significant weight gain with the Lanifibranor doses. But this is another promising program with good efficacy.

Naim Alkhouri: And Novo Nordisk with semaglutide also had an impressive press release. This was a longer study, seventy-two weeks, and they assessed histologic response to three doses of Semaglutide and they showed actually resolution of NASH in 59%. So, this is one of the highest rates we’ve seen when you use the high-dose semaglutide. Of course, semaglutide is on the market as a diabetes medication. It has proven efficacy in reducing A1C levels, a positive effect on lipid profile, but most importantly, it has proven cardiovascular outcomes. And we know that patients with NASH die from cardiovascular disease more than even liver disease. So, this is very important. This is a promising drug that will also target metabolic syndrome.

Naim Alkhouri: And then, finally, I wanted to mention also the Gilead program, that they did a trial looking at their compounds with firsocostat and cilofexor, in addition to the Novo compound, semaglutide. So, given the biological complexity of NASH and multiple pathways involved in disease progression, it makes sense to look at combination therapy, and this is going to be three drugs looked at and one pilot. But I look forward to looking at the results at the ASLD meeting. So, several promising programs, I think the future is going to be bright for us, and we’ll have FDA-approved medications hopefully next year or two.

Roger Green: Thanks, Naim. Great way to get us started on this.

Louise Campbell: I just had a question. All of those sounded excellent and great responses. What happens when the person comes off the clinical study, and therefore, stops the medication? Do you know what the outcome is? Is there a followup study for discontinuation of the medication, and if so, do you see a recurrence of the disease?

Naim Alkhouri: Yeah, that’s an excellent question. I think seeing in older trials, when we used pioglitazone, vitamin E, that when you start the medications, the liver enzymes go up, indicating that maybe the diseases are coming back. Some of these programs, they did very short term studies, as I mentioned, sixteen weeks, twenty-four weeks. We have some potent drugs, so we will see how the future shapes up, but it might be that we use very potent drugs for a period of time, get them to a better place, and do some fibrosis regression. And then, you have to keep these patients on a maintenance drug that could be easier to take with less side effects. But there is the possibility that many patients with advanced fatty liver disease will require lifelong therapy. Very important topic.

Roger Green: Naim, one of the presentations I talked about out of the digital ILC meeting was from Hanmi Pharmaceuticals in Korea, and their compound, I think it’s 15211, if I remember correctly, which is a combination, GLP-1 GIP glucagon triple agonist. And they showed some remarkable early stage results accompanied by a safety profile that didn’t appear to have any obvious major flaws in it. Do you believe that, at the end of the day, those compounds will supersede the roles that the single entity GLP-1s play, or do you believe that each will have a place as you see going forward?

Naim Alkhouri: You’re absolutely right. And there are other compounds with AstraZeneca. They have the GLP-1, glucagon. Other companies have similar compounds. Lily have a very potent GLP-1 GIP. I think it’s to be determined just because you have more mechanisms of actions, it’s not going to always translate into more weight loss and efficacy in terms of NASH. So, I don’t think we have a clear answer yet. A similar story also with PPARs, as you know, PPAR-gamma alone versus pan-PPAR, versus PPAR-alpha-gamma. I think I like to see the data before we just decide based on mechanism of action.

Roger Green: I’d be remiss not to mention that I think Altimmune also has a glucagon GLP-1 GIP triple in pipeline. Donna, do you have question?

Donna Cryer: No, that’s fascinating, and I’ll leave the science to the scientist. I think that one of the strengths that I hear reinforced in that is the diversity of mechanisms across the research landscape. And certainly, I see my role as reinforcing and supporting that diversity, rather than have it foreclosed too soon at this early stage in the field.

Roger Green: Amen. I’ve got one more question. Naim, a couple of episodes ago, I want to say it was 25, but it might’ve been 24, Steven was virtually pounding the table, and each time Steven starts with, “I want to make a controversial statement,” my ears pickup. He did that here. His controversial statement was that if we really want to expedite drug development in the field, we will take the very best agents that we’ve got and put them together in combinations instead of running them out as monotherapy and reserving combinations for the things that have not performed as well as monotherapy.

Roger Green: A: I’d love for you to comment on that in general, and B: if you can think of any specific combination therapies of agents that appear to be robust, for example, what would you put on top of the Akero molecules as combination therapy, or what would you want to take out with Lanifibranor, just to use two of the ones that you talked about?

Naim Alkhouri: You can think about combination two ways. Number one is to increase efficacy, but, number two, to mitigate some of the potential side effects. So, for example, semaglutide looks great: you lose weight, you improve A1C lipid panel, and you have NASH resolution, but they didn’t show fibrosis improvement. So, I would love to combine it with a drug that has proven antifibrotic effect, and the largest data set we have is with obeticholic acid, for example. And maybe by using semaglutide, you can mitigate the negative effects on the lipid profile related to using OCA.

Naim Alkhouri: So, I think this is how I think about it. I think lanifibranor, in terms of efficacy, it showed great efficacy, but also the weight gain is not something to neglect. So, maybe if you combine it with a GLP-1 that induces some weight loss, that could be one way to mitigate that and maybe enhance the NASH resolution aspect. I think the future is full of possible combinations. We’ll see how the field shapes up, but I think definitely there is room for improvement in terms of mitigating side of the effects and increasing efficacy.

Roger Green: Those are great answers Naim. Thanks a lot. Louise, you have another question or shall we go on to Donna, who I think is next on our list?

Louise Campbell: I didn’t have another question. I think it’s just very exciting to have multiple agents in the pipeline that are showing great efficacy and hope and a very quick improvement in liver condition. So, that’s encouraging, but with a long way to go.

Roger Green: Naim, thanks for an

Roger Green: Excellent opening statement and great question [and] answers. Always a pleasure having you here. Thank you so much. Donna, you’re up next.

Donna Cryer: Thank you. So much of this evolving field of NASH is what we make of it. So my predictions are as much aspiration as signaling as to what I intend to do and where I’d like the field to go. When I think about the next few months, given what the last few have looked like, I really think about regrouping to be able to press forward. And what I mean by that is reassessing the progress that we’ve made and thinking about how we can sharpen our arguments, add more data to things that are working and really get even smarter about where we’re trying to take the field. And so an example of that would be working more closely with the type two diabetes community, both patient and clinician. And Naim, the paper that you worked on with Dr. Noureddin and others is an excellent example of providing more evidence on the enhanced value of screening in a type two diabetes population because of the highest prevalence of NAFLD and NASH that we know, but we haven’t done such a great job of proving to the point where every endocrinologist, every diabetologist is sitting up paying attention and wanting to move forward really aggressively with us. We’ve seen great partnership from folks like Ken Cusi and Rita Basu And the Endocrine Society and ACE.

Donna Cryer: And so I really think that focusing on the type two diabetes population who are not only more likely to have NAFLD or NASH, but to have an advanced form and while from a literally a global perspective and add larger advocacy perspective, it doesn’t mean I’m taking a step away from the earlier stage NAFLD or NASH or prevention, but I think what I’ve been really listening to the field and so many different groups of advisor calls with folks from around the world is that we still have a job to do in terms of convincing the larger clinical populants that NAFLD and NASH is real, and that there’s an urgency around it.

Donna Cryer: Getting that sharper focus on NASH and type two diabetes is really an important thing to increase traction on in this next few months. And I think that job of convincing translates into the work that we need to do in the regulatory space, on the urgency around NASH drug development. I’m seeing a disturbing pattern across all forms of liver disease in, it seems to me, a misperception and a misunderstanding of the urgency of evaluating and approving surgeries, therapies, medications in the liver field. And so from a patient perspective, putting together patient focused drug development, supporting those already in progress and making sure that we have robust data on patient perspectives, patient risk and benefit, from the very large and yet diffuse and heterogeneous NASH patient population and putting that in front of regulators in an undeniable way is certainly something that I will be focused on over this lovely autumn.

Naim Alkhouri: I just wanted to thank you, Donna, for mentioning the cost effectiveness paper that we published that shows that screening for NAFLD in a diabetic was fifty-five year old, and then providing the intervention being intensive lifestyle modifications was actually cost effective. I think you noticed this is something we’re pushing for now to screen all diabetics. The screening also can vary from liver function test to ultrasound, to also considering a fibroscan test on every diabetic. And I know a few diabetes clinics that do this routinely now, so same way you do your foot exam, your eye exam. You also do your fibroscan and this way you can screen for fatty liver with the CAP score, and then you can find advanced fibrosis with the liver stiffness as measured by the fibroscan machine. So, as the availability of these technologies increases, I think it’s going to become standard of care that we screen all diabetics.

Roger Green: So, Naim. Louise is only 6,000 miles away from me right now. And I can still see her nodding her head up and down enthusiastically as you talk about the idea of screening type two diabetics with the fibroscan.

Louise Campbell: It was interesting because I was listening to him there and I was listening to Donna and I did some screening a couple of weeks ago in three homeless locations. And there was only a few of them with any concerns from their liver stiffness. However, over 70% of them had high fat steatosis grade three, and we know fibroscan is not as accurate as dynamic fat fraction, but as Stephen continuously anything over 280, we would expect to see replicated on liver biopsy. So most of them had either, or several of them to be fair, had either been diagnosed as diabetic or in prediabetes conditions or had cardiac conditions.

Louise Campbell: So maybe we shouldn’t be so worried about our drinking and drug using populations from a liver perspective, but maybe we should be from endocrine and cardiology perspective because they were all really amazed that they had decent livers and were actually really excited that they could actually still save their livers. So the buy-in and the turnaround for the people that we scanned was absolutely amazing. It also challenged some stereotypes that some of the care workers had that everybody who drinks eventually has damaged liver. So it was very good sessions, but yes, I was smiling when Naim was talking about just being able to assess. And I think it is personally quick, because that’s what we provide. We provide that access, but looking in the drinking communities, their liver was fine in the majority, but over 80% of those had high liver fat, which was more of a concern.

Roger Green: This is a composite question. I’m going to see if I can hit at least two, maybe all three of you with the same question. One of the things we’ve talked about a couple of times in the last few weeks was the presentation from Zobair Younossi’s group at Digital ILC that looked at every death certificate issued in the US in the year 2017 and came to the conclusion that the leading cause of death among NAFLD patients was in fact liver disease. We talked last week about how that might lead us to refocus how we think about the benefit of treating earlier stage. Louise, what you just said aligns really neatly with that kind of a perspective.

Roger Green: Maybe the liver isn’t indubitably damaged yet, but the high fat portends bad things for the future, not just maybe for the liver, but also cardiovascular. Bu to Donna, first of all, how does that kind of thinking influence what you’re working on and what you would like to see happen going forward? Does that make it harder for a liver advocate, easier for a liver advocate or it just changes the message a little bit? And then to the rest of you, what do you think ensues as the result of that over time, if anything?

Donna Cryer: I focus on liver disease and deaths from liver disease can only make our message more impactful. And so to have that evidence is so very valuable. The Global Liver Institute have always discussed a solution for every stage. And then the solution at earlier stages may be more intensive lifestyle interventions perhaps supported on making sure that there’s coverage for dieticians or additional types of support so that people can be successful in that, at that earlier stage.

Donna Cryer: But what it means and what my earlier message about shifting strategy or shifting emphasis of our strategy remains the same that I think that in our listening and in the totality of the evidence that a particular focus on those with type two diabetes will give us greater traction to be able to treat everyone. We don’t have that buy in and traction yet to be so diffused. And so I think by targeting in a population for which the ROI of the work is so clear and can satisfy all of the audiences involved, whether that is a clinician, a patient, a payer, a health system of making these initial investments that allows us to make the case and we keep going up the stream.

Donna Cryer: We can go up the stream to people who are not diabetic or not at an advanced stage, but if we can’t even get attention for those who are showing up with concomitant diagnosis of NASH and liver cancer or NASH and needing a transplant for the first time, making the argument about investments in care for folks who are early in the stage is harder. So I just think it’s a reordering and a refocusing, but the intention is certainly to leave no patient behind, because I have to use a military term if Stephen isn’t here and represent. So we want to make sure that we leave no patient behind, but I think from a strategic point of view of focusing on these at risk, high risk advanced patients, particularly with diabetes, is where we’re going to be heading.

Roger Green: Great answer and great presentation. Anybody with a final question?

Louise Campbell: I thought it was a great presentation and I echo Donna’s sentiments there. And I think eventually, we have to accommodate from both ends to get better outcomes. We have to treat the most severe disease first, but we also have to target to prevent people getting the disease or any of these diseases in the first place. So it has to be two-tailed. Push me-pull you: is that not the thing in Dr. Doolittle?

Donna Cryer: Yes, I love it.

Roger Green: Good, good, good, good. For the rest of the animal kingdom, we thank you. And Louise, why don’t you go onto your topic?

Louise Campbell: My topic is one that I regularly bring up, I suppose. It’s more about the wellness aspect and the sustainable development goals. And I think recently, the Lancet produced the Poverty Commission, which was bridging the gap in universal health coverage. I think it was the last week, the 14th of September.They did a summary of the SDGs in the poorest billion and they expressed some concerns about the five-by-five model favored by WHO, which focuses on cardiovascular disease, cancer, diabetes, chronic respiratory disease and mental health. We know that poor liver condition and NAFLD and NASH are involved in cardiovascular disease, cancer and diabetes, and also affects mental health. But the elephant in the room is it’s not mentioned in those five diseases, but it’s intrinsic to four of them. And the five risk factors: tobacco use, unhealthy diets, physical inactivity, harmful alcohol use and air pollution.

Louise Campbell: So again, the elephant in the room is all of that is about lifestyle acquired and affects the liver.that’s three out of five of those. And I think, is it possible to target a sustained goal, which is this is 3.4? The aim is to reduce mortality in NCDs by 2030 by about 30%. But can we solely rely on better health techniques in those five areas and not account and attribute for the growing population of those patients and ignore one of the biggest causes or contributors? Obviously, we don’t have the exact mechanism that NAFLD and NASH are involved in diabetes. And there are certainly studies whereby you can get people with NAFLD and NASH who do not have cardiometabolic syndrome. So I think it skews out, but we know that there’s a connection there somewhere. We just haven’t got it.

Louise Campbell: I had a look at the Economic Forum report, because up until 2010 chronic diseases were considered in the Top three of the biggest threats to the global economy and within the top four of the impact. But they suddenly disappeared. Pandemics were included in that as well, but they suddenly disappeared in 2010. And I wasn’t sure what happened, to why we suddenly lost track of healthcare being a significant contributor to the global risks. And yet this year we’re obviously paying for that. So 2010, they disappear off the global, the economic forums reports, life expectancies increase.

Louise Campbell: So I think wonder why they went on to do that. So it’s very, very difficult when I look at where we’re heading. And I appreciate what Donna said about the research. I also appreciate what all of the international liver areas do and consultant colleagues, and it is about the evidence, but it’s very difficult to avoid the correlation with the rise of liver disease. Liver cancer is one of the biggest growing threats to prevent the MCD completing the task of improving health and reducing mortality. Australia leads the world in its rise in liver cancer. And I think we have a massive problem with liver cancer all around the world. And if the first time in health care we mention liver disease is when we’ve got to cancer,

Louise Campbell: We have all missed catching the ball for a long time. Given the length of time it does take, which is why when Donna talks about Type 2 Diabetes, it’s intrinsic. They have a four times greater risk of developing liver cancer. So if I was Type 2 Diabetic, I would be putting my hands up to my doctor and saying, “Please test my liver.” And when I have that conversation with Type 2 diabetics about the discussion about your liver fat, nobody’s ever mentioned it. But I think it does continue.

Louise Campbell: But I think, coming to a close on that, there was a very interesting session that I attended at the digital ILC, which is EASL are now combining the International Liver Foundation with a group to bring this now towards the SDGs. And it was a UK think tank, Wilton Park and EASL. I think there’s a number of stakeholders involved. I’m not too sure whether Donna and the GLI are involved, but they do say global patient advocates. So that’s really encouraging that we are now starting as a liver community to start that dialogue at these sort of global level.

Louise Campbell: I think it has to happen. We have to get liver disease and screening at the table. There was also an EASL or European funded project called Liver Screen, which is looking at exactly what Naim was talking about earlier and that I advocate is that placing fiber scan earlier in the timeline helps, but that’s a five year study and it’s looking at who we should be screening. So there’s lots of good things coming out. I hope that they will look at the evidence and provide a lot of the evidence that we’re all discussing now. But I just also had a thought that maybe we need to take it out the silo when I looked at the people who are around the table, hepatologists, NCD specialists, public health advocates, they all come from an area of illness. So they’ve all been affected or look after people who are affected. I would have liked to have seen wellness or lifestyle medicine there because a lot of it has to go about prevention as we discussed earlier in this episode. And I think we do have to look beyond the past and the current medical straight jackets that were held within our thinking. But what if chronic diseases just comes down to a lack of education? How you actually look after yourself physically, socially, mentally, it’s not a topic I ever covered or was taught in school. You can come out knowing the mechanics of the car, but then you can come out knowing the mechanics of your body and how to look after it. So if we took it back in every school, maybe we should get educated around these health teams because bringing back education into schools about how you look after your body, from when you first attend school to at the end of it, you may always grow up knowing how to look after yourself, which comes to the prevention of NCDs in the majority of people if we know how to look after our health and our liver health. And I think it is encouraging now to see liver starting to be at the table to discuss the sustainable goals, because that’s actually quite exciting because hopefully we will get APASLl (sp?), AASLD and everybody else around the table for that, because we have to be there. So that was what I was bringing and over the next three months, whether or not we’ll see much of that happen because of the pandemic rising throughout Europe again, I’m not too sure, but it would be great to see some movement around that table.

Roger Green: That’s great, Louise.

Donna Cryer: I just want to underscore that and clarify that, yes, the Global Liver Institute is the aforementioned patient voice that is at that table for NASH and for other things in the Wilton Park effort. We were founded really for that purpose to place liver health, not just liver disease, but liver health as part of the global public health agenda commensurate with its prevalence and impact. So that has been our vision since our founding. We are a member of the NCD Alliance. So part of that, global alliance to focus on noncommunicable disease and those sustainable goals. And it’s been fantastic to see just in the past few months, a momentum towards doing that. Certainly when we were able to add an office in Europe that helped our ability to make those partnerships with the UN and the WHO and with EASL and others to sort of light a fire under all of that.

Donna Cryer: It’s been really exciting, the traction. I think that NASH provides a particular opportunity that we hadn’t really seized on in other liver diseases. Even when we had the excitement around the Hepatitis C cure the focus wasn’t really on the cure, perhaps it got weighed down in a lot of other controversy. And we didn’t really talk about liver health because of the interconnectedness of NASH to other conditions, which you so well articulate. I think this is our time. This is our opportunity to really position liver health, alongside cardiovascular health and other things that have that type of recognition and have that type of investments addressing it to bring that to liver health.

Donna Cryer: So I’m really excited about that and could not underscore your point more fully. I end this on the question of education. Is it so much that people don’t know what to do or they have a hard time doing it? Is it the knowledge per se or is it the coaching or the peer group helping reinforce what we know we need to do every day? Which one should we be weighting more heavily on, the education or the support function?

Louise Campbell: When I thought about it, I thought about the education. If you go into school, it doesn’t matter which school, we know that education throughout the world is different. And I think just if it’s in your own region, at the age of four or three or five or six, when you’re going to school, you have a session a week on actually what’s happening with your body. Where are the bits and pieces? How is one organ connected to the other one? I used to learn the ankle bone was connected to the shin bone. The shin bone was connected to the knee bone, but actually we forget that throughout healthcare. Our body isn’t siloed. Your liver does more in one second that we’ll ever know in its lifetime, in our lifetimes. And I think, if we actually know why we’re walking to keep fit, why a healthy diet keeps us fit, and our sleep helps our mental health. And if our liver’s overweight, it can affect our skin or tiredness or levels. And if we actually understand that, I think it doesn’t matter where you are in the world. If you actually understand and have that education, you know why you might be taking less care or not as good care.

Louise Campbell: I think, we wouldn’t think twice about spending four years in braces to correct our teeth, but we don’t think that of spending four years looking after our weight to reduce it. We want an immediate fix. Whereas if we’re educated that that’s not actually how our body works, you can take that pressure off yourself. But you might actually prevent people getting it in the first place because people are more savvy. If you liver never gets overweight, you may never develop high blood pressure, high cholesterol, arteriosclerosis. We’ve got to prove those yet, but the theory is there. So if you educate a child to keep fit and healthy throughout their adulthood, then hopefully we will introduce the theory being that we would reduce the amount of people that develop those other NCDs, because that’s what we’re seeing around the world.

Roger Green: Louise, I agree with you, but the forecaster in me thinks about it this way. If we start treating kids in school, picture this as if this is a hose, water hose of patients. And we have patients of all ages, but we have patients in their 20s, 30s, 40s, 50s, even 60s, getting into places from which their health will be vitally damaged for the rest of their lives. If you put your foot on the water hose, when someone is five, you can stop what goes into the hose but the literally billions of people that are going to tumble out that hose before it’s done, suggest that that’s part of the solution but at the same time, I think we also need to have a solution for how do we educate adults, which is tougher because generally now we’re educating people who are sick. You made the comment before, which I thought really was exciting about being able to go to people who are drug and alcohol effected, show them that they hadn’t destroyed their livers for good yet and get them to be enthusiastic about how to practice better behaviors. Now, Steven’s comment about a lot of that stuff has been, there’s a reason there’s no sequels to the show, “World’s Biggest Loser”. You go back a year later, it’s not clear what you’ll find, but if you could get those people excited and people with less severe problems excited, and then we had a way to help them educate and change behavior in real time, while at the same time dealing with the children, then I think you’ve got a two pronged approach. And I think if I had to give up one or the other, I’d give up educating the five-year-old, but I’d like not to have to give up either. Does that make sense?

Louise Campbell: It does make sense. And I think, I see so many people, and I’m sure every physician and Naim and everybody will say, “Oh, is that where my liver is? I thought I had two.” And it is, we come out of education systems, we might know the chemistry, but we just don’t know about ourselves. And yet ourselves are the biggest investment anybody can financially make, because if we’re fit and healthy, we’re a competent workforce. And I think people will still eat the wrong things. People will still not exercise, but actually you make a conscious choice because you know a little bit more, and I think, Maya Angelou once said, and it’s a favorite quote of mine, “If I’d have known better, I’d have done better.”

Louise Campbell: Actually, our children don’t know better. And a lot of those adults don’t know better and I’m forever being educated by my stepchildren. They love to come home and go, “Guess what I learned today?” So I would hope, yes, it will be a two pronged approach, but it’s a cheaper approach to spend an hour of education a week for the ten, twelve, fifteen years they’re there than actually to spend millions and billions on medication. So it’s a long term approach, but it needs to be around the table.

Roger Green: I think there’s investment and there’s expense. What you’re talking about is investment and will be amazingly efficient. And then in the meantime, we also have to manage what’s more directly in front of us. I completely agree with you on that.

Donna Cryer: I want to mention here, our friends at NASH kNOWledge who have started a pediatric NASH education program using the Oliver and Olivia coloring books that Thelma Thiel, longterm liver health advocate, who was on the GLI founding board and who unfortunately lost her child to a pediatric liver disease, the work that they’re doing in this area to bring liver health education into schools. So people should support that.

Louise Campbell: Yeah. Excellent initiative.

Roger Green: Agreed.

Naim Alkhouri: Yeah. Just wanted to mention something briefly. We have an epidemic of NAFLD alcoholic liver disease, but we are learning more about something now we call both alcoholic and nonalcoholic fatty liver disease. We recently published a paper and now we call it BAFLD, B-A-F-L-D. You know, this is a true problem. And when you have people drinking four or five drinks a day, but they also have Type 2 Diabetes and obesity metabolic syndrome, I truly believe it’s not just the alcohol. I think it’s both NAFLD and alcoholic liver disease combined.

Naim Alkhouri: The other point is that recently the Dietary Guidelines Advisory Committee recommended that men should decrease their daily alcohol intake to the same level as women. So we used to say, it’s okay for a man to have two drinks a day. And now it’s just one drink a day. And we need to really just admit to ourselves that, drinking alcohol, probably the benefit is exaggerated and the risk is real. So the way I think about drinking alcohol now is like smoking cigarettes, nothing good is going to come out of it. I think the cardiovascular benefit has been heard on, but I’m not a believer. And I see all the bad things that happen with alcohol. So, education is important, but I would like to get that message out that the less alcohol you drink the better it is for your health. Especially if you have advanced liver disease.

Roger Green: Thank you, Louise, for, a really instructive and important set of issues about thinking about liver disease in a way that people who aren’t in this community don’t think about it. And maybe people who are in this community, don’t think about how people who aren’t in this community don’t think about it. I know that’s a really complex sentence, but I think it hits the point.

Roger Green: All right, so I want to spend the last ten or twelve minutes, we’d be remiss if we didn’t talk about COVID because COVID overhangs everything, and we don’t have a ton of time on this podcast. We will come back in two or three weeks and do an episode on COVID, I promise. But for today I want to touch on some things that I think are related to what we’ve been talking about.

Roger Green: Number one, the hypertension on COVID, the fact that so much attention is placed on it and it’s part of everybody’s lead news stories every day and case counts and death rates and all that stuff, and the politicization around that. It drowns out a lot of the space that people would use to talk about, learn about, or think about other more subtle health issues, like for example, liver in the way that Louise was just describing. I think that’s number one.

Roger Green: Number two, Apologies to the audience. We try very hard never to talk about politics in any shape or form on this program. We certainly don’t endorse anybody, but there are things that just have to be mentioned in this conversation. So for example, in the U.S., in the last 24 hours, the secretary of health and human services announced that he, not FDA, would have final decisions on drugs and vaccines going forward. And the CDC website, which had posted that we now understand Coronavirus to be airborne, took that down and went back to the position that goes, “It’s mostly by human contact and touch.” When in fact the overwhelming consensus is that this is an airborne disease and airborne management is going to be pivotal to its longterm social effect. Unfortunately, we’re in the middle of a political environment and we have a president who said one thing on tape to Bob Woodward and another thing to the country. So CDC has now reverted to what he said to the country.

Roger Green: Science makes mistakes because science is an open-ended inquiry. We go with the best information we’ve got. It’s not always very good. But it’s an honest inquiry. And if we get to the point where we start managing scientific information to meet anybody’s political ends, and by this, I mean, not just say what I just described, but also people with other political persuasions who are

Roger Green: managing evidence in very different ways to their own ends. We damage the ability to put COVID in a realistic context. And therefore to really trust anything in science, we’re already seeing a decrease in belief in vaccine among people whose historically thought vaccines are great because of the politicization they perceive around a COVID vaccine. In the middle of all that, even in the middle of a COVID discussion, we’ve seen some papers earlier in the year about the idea that prior NAFLD might be a predictor of severity of code infection, but we’re not seeing that getting a lot of traction. I’m not sure that there’s enough oxygen for it to breathe right now.

Roger Green: So, those three collective issues, the over-focus on COVID and the politicization of COVID data and the idea that folks are using it for politically driven agendas, I think makes it tougher for the liver community to do the things that we need to do to educate and get attention right now. I don’t know how that plays out, but I think it’s something we watch carefully over the next three months.

Naim Alkhouri: These are excellent points to Roger. And I just wanted to comment on COVID and NAFLD. Number one is our patients with NAFLD have a lot of comorbidities that definitely increase your risk for severe COVID. So, on average patients with NAFLD, 80% have overweight obesity, about 45% have type two diabetes. And then about two thirds have hypertension. Data from the Chinese CDC showed clearly that patients with obesity and type two diabetes have higher mortality rates related to COVID. And these are very common in our patients with NAFLD.

Naim Alkhouri: More recently a study also from China looked at two-hundred patients that were admitted to the hospital with COVID. And they looked at NAFLD based on liver ultrasound that showed fatty infiltration or something we call the hepatic steatosis index. Which is an easy way to determine the presence of fatty liver. And they showed patients with fatty liver were more likely to develop severe COVID, and to also have a longer virus shedding. So, I do believe that NAFLD patients are considered high risk for severe COVID.

Roger Green: Thanks Naim for that same reason, I’ll be very intrigued to see what happens when Perspectum starts talking about the COVERSCAN work, tomorrow. The earlier Perspectum UK Biobank paper suggested that NAFLD was a stronger, independent predictor of COVID severity than the comorbidities with which it’s associated. As they start to roll out a multiorgan look, it’ll be intriguing to find out if that’s confirmed, reversed, minimized, maximized, whatever. And then whether it gets any oxygen or air play. I think your points though about, and your summary of the work that’s been done is really excellent and very valuable. Thank you for it.

Donna Cryer: So, as we at the Global Liver Institute have been trying to guide patients from early March through this pandemic. I so appreciate the rigorous scientific work that has been done to give us more information on how COVID is impacting liver patients. Those with NASH, patients with liver transplant recipients that are otherwise immunocompromised, the different registries, secure and the pediatric liver transplant registry, that have been set up to get us the actual factual information that’s necessary to make decisions.

Donna Cryer: I think to your overall statements, Roger, we have to do everything possible to reinforce reliance on and support for the production, collection and dissemination of actual credibly produced science. Our lives depend on it. So, my heart and every type of support goes out to those scientists, those career scientists and researchers and public health officials throughout the United States governments and in governments throughout the world, who are valiantly trying to get out accurate information to the public and others, so that we can make decisions. As a liver patient right now, I think it’s very important for patients to understand what a safe healthcare environment looks like.

Donna Cryer: And to either ask their clinic, “What steps are in place.” But to go and to get their blood work, their screening, their followup tests. Liver cancer is not stopping progression, if you we’re placed on the liver transplant list, you’re not getting better during this time. So, there is an urgency about having patients continue to seek non-COVID related care. And as health systems are increasingly sophisticated in providing both COVID and non-COVID care, as we know we’re about to go into both COVID and flu season very soon.

Donna Cryer: Patients should be getting their needed care, not delaying it. They should get their flu shots. I just got mine. They should, if they can, sign up for COVID- 19 vaccine and therapy research, so that we will know that it works on liver patients. All of that said, there is not a COVID-19 vaccine that you could pay me to take before November. There is nothing you could tell me or show me at this point, because the political damage is so done, that I, as somebody who has been in healthcare now for more than a quarter century and has been in Washington D.C. For all of that time. There is no vaccine, no COVID-19 vaccine that you could get me to take before November 3rd. So, I’ll simply say that as I continue to wear my increasingly diverse set of masks, wash my hands and social distance, even though, as I go out and about as necessary.

Louise Campbell: I just think we’ve obviously plastered all over our society about losing weight, about going on soups and shakes to help people lose weight. The NHS have produced an app. I actually did write to Boris Johnson in May, saying that in lieu of no vaccine, possibly our biggest ability to help populations like the type two diabetes or the 14.3 million we were expected to have NAFLD, was actually that weight loss may well be our biggest ability that people can do now, to help their own health. And I think going back to Donna’s comments at the very beginning, the purchase to be able to now work with… that she’s getting with diabetes. They are some of the biggest populations at risk. And I think it is a shame that any political agenda can detract from patients or people learning facts that could help them get a better outcome from COVID.

Louise Campbell: Going back to the Biobank, that was 10% body fat and more in obese patients, doubled your risk of severe COVID in an outcome. Whereas normal liver fat in people who were obese, did not increase their risks at all. So, that was what you were on about, Roger. And I think it will be very interesting. We can’t necessarily dynamic fat fraction everybody, but I think the strength of the evidence that, that can produce is colossal. And it carries a lot of points. So, it’ll be interesting to hear what they say. But it’s a shame that any political agenda gets in the way.

Roger Green: Thanks all of you. In wrapping up, I want to make one thing clear. It is not my intention to endorse a political candidate or party. There are many reasons to vote for any candidate for office, without dealing with this particular set of issues. But facts are stubborn things. There are facts around these set of issues and in the context of what we’re talking about today, not who you vote for, but how you deal with issues around liver disease. Those are facts we need to deal with. So, I hope everybody gets the context right, and understands what we and aren’t saying here. And with that, I’d like to wrap up today’s episode. Closing question, same question we usually ask. What’s the biggest surprise you got today or the one thing that you learned or thought about while we were on podcast?

Donna Cryer: Louise made me believe in education again. And if everybody educated or taught health at school and made it as relatable and relevant as Louise did, we would have healthier people.

Naim Alkhouri: I learned a lot about all these initiatives to increase screening, especially in underserved communities. And this is great. And also to engage the Endocrine Society and the diabetes specialist in our efforts to increase awareness of NAFLD and the burden of liver disease in this population. So, it’s refreshing to see everything you guys are doing. Thank you.

Louise Campbell: I’ve got two things. I’ve got the work that Naim was talking about, doing scanning and keeping patients into clinical trials, which I need to look up and read that. Because that sounds exciting. And also absolutely reassured that Donna and GLI are around the table with EASL, the International Liver Foundation and Wilton Park with the Healthy Livers, Healthy Lives work. So, both of those. So, congratulations.

Roger Green: Excellent.I’m with Donna, I think. I’m appreciating the importance of education. But one of the things I was realizing, almost as I was speaking, is that it may be that one of the best ways to educate people in their thirties and forties is to do what Louise described: have their kids come home from school and tell them what they learned. They may be much more able to observe that way. And I know a bunch of people who over the years quit smoking mostly because their kids got on them to quit smoking. So, ideally education can not only be directly efficient with the kids, but drive that kind of support as well. And that would really be a fantastic double.

Roger Green: With that, time to wrap up. Please come on the discussion groups, tell us what you want, our ASLD coverage while we’re still planning it. So, that you don’t get to the event and go, “Gee, I wish they had done that.” This your opportunity to tell us about it.

Roger Green: Special, thanks to everyone who makes this podcast happen. Obviously, Louise, Donna, Naim for being able to come on today. Mic Wilson, our engineer. Buzzsprout who publishes our podcast. Eric Rounds, who runs our social media. Politeia Le, who runs the media. And Ryan Segura, who edits all this. Thanks to you folks who help, and as we continue to grow this and make it the entity that it’s becoming. We will be back next week. I don’t know what we’ll be talking about exactly yet. I think there’s a chance it might be COVID, there’s a chance that it might be diagnostics, there’s a chance it might be something that hasn’t come up yet. But Stephen will be with us, as will Louise and Donna, and we’ll see who else. We look forward to speaking with you soon. Hope you join us again next week and stay safe. Surf on. We’ll see you on the podcast. Bye-bye now.

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