Ep. 10 Diagnosing diagnostics II – tools vs. teaching

What would create greater value for patients and providers?

Professor Mary Rinella of Northwestern University and Suneil Hosmane of GenFit join Stephen, Louise and Roger to explore which of these strategies can do the most to improve patient diagnosis and management. The answer might surprise you.


Hello, this is Professor Mary Rinella of Northwestern University and you’re listening to Surfing the NASH Tsunami.

Drug developers, investors, researchers and corporate executives wrestle weekly to understand what is happening in commercial development of NASH medications. Join hepatology researcher and key opinion leader, Stephen Harrison, C-suite veteran Peter Traber and forecasting and pricing guru Roger Green as they discuss the issues affecting the evolving NASH market from their own unique perspectives, on this week’s edition of Surfing the NASH Tsunami.

Roger Green (00:00:35): For everyone with an interest in NASH or more broadly in fatty liver disease, surf’s up, because Episode 10 of Surfing the NASH Tsunami starts now. Hey, audience, we’re in double digits. This is Roger Green. I’m the host and executive producer of Surfing the NASH Tsunami, and this Episode 10. When my friend Stephen and I decided a couple of months ago, it might be interesting to do a podcast about COVID and NASH, I don’t think we had a plan for how to get past about the third episode. But here we are, seven weeks later with thousands of you subscribing in 15 countries around the world, and we want to thank you, this has really been a tremendous experience, and frankly, a lot, a lot of fun.

Roger Green (00:01:11): Last week, we talked about the celebration of International NASH Day, or as Donna was surprised to hear me describe it International I-N-D Week, which is now going to try to turn into IND month. But after that, this week, we’re going to shift towards a more scientific theme. Two weeks ago, if you remember, we had a session called “Diagnosing Diagnostics, Part One,” where we talked about what we have today in terms of diagnostics and why it works and frankly, where it needs to be approved.

Roger Green (00:01:40): Today, two weeks later, we’re going to come back and look at where non-invasive diagnostic testing is heading. We’re fortunate to have Suneil back, and to have with us Dr. Mary Rinella of Northwestern University, who has published some of the really interesting and important work in this area. Stephen is here as well. Louise is here as well. Unfortunately, Peter is not able to be here, and that’s unfortunate in many ways, but fortunate in that if you’re the moderator, you don’t have to try to manage six people at once. That’s a massive headache. Peter, I’m sorry, you’re not here. Thank you for sparing me a headache. With that, everybody, let’s get started.

Roger Green (00:02:15): Kickoff question this week, one personal highlight of the last week. Something really good that’s happened. Louise because I know what you’d like to talk about, I’m going to give you a dispensation to make the personal and the professional happen at the same time, if you would like to kick off right now.

Louise Campbell (00:02:30): Thank you, Roger. Yes, I’d like to do, as you say, both a professional and a personal highlight, and it’s the fact that I was one of the experts for the FibroScan for assessing liver fibrosis and cirrhosis in primary care, which was a document released by the National Institute for Health and Care Excellence in the United Kingdom today, talking about and allowing GPs access to encourage early diagnosis of liver disease, also to look for diabetes, hypertension, cardiovascular.

Louise Campbell (00:03:00): Hopefully, this will give primary care access to further upstream diagnostics to better guide them to use other non-invasive techniques and refer the right patients into secondary care. From our perspective, that means patients could get less appointments, they could also not wait six months to get an appointment sometimes, and particularly given that FibroScan is predominantly held in the UK in secondary care, hopefully, it’s an opportunity to get it now out into primary care that we’ve got some national guidance for that. It’s a both a professional and a personal highlight, and I’m really pleased to see it come out quite nice.

Roger Green (00:03:39): Well, then congratulations and congratulations, not necessarily in that order, but that’s fantastic. Suneil, why don’t you step in?

Suneil Hosmane (00:03:45): I just happened to switch to Geico. I’m just kidding. I really did do that, and I did save 15% but that’s neither here nor there. We’ve been locked down during the quarantine. I have two little kids, one that’s coming up on one and the other one that’s three. We’ve done nothing but staying at home, walks around the home. But finally this weekend, the weather got nice, and we went out to a lake and went miniature hiking, like, through the woods nearby. It is really nice, really special.

Roger Green (00:04:13): Okay, that’s great. Mary?

Mary Rinella (00:04:16): Hello, and thank you for having me. It’s really a pleasure. Personal highlight this week was that I actually planned a vacation to go to Montana because I feel like since COVID started, it’s been one continuous day that’s never ended. I’m looking forward to just getting out of here. Then I guess professionally, one thing that may pertain to an episode you guys did earlier, I think, is on the whole NAFLD debate and our commentary in Hepatology was just accepted. Hopefully, the other side will be voiced in a public forum starting soon.

Roger Green (00:04:51): Excellent. Stephen.

Stephen Harrison (00:04:52): Well, again, welcome everybody. Thank you for joining us on Episode 10. Personal: I have learned how to surf. This is Surfing the NASH Tsunami. I don’t live near a beach, so, I can’t surf on the ocean, but I can surf behind a boat. I learned how to do that about two or three weeks ago. I’ve actually learned how to let go of the rope and surf behind the boat without being pulled by anything except the force of the wave. That was really fun.

Stephen Harrison (00:05:21): Of course, I do that listening to my favorite band that my daughter introduced me to called 21 Pilots. There is a recent song out about the COVID epidemic called, “Level of Concern.” If you haven’t heard it, I encourage you to listen to it, it’s fabulous. I surf to that song. That was personal, just really kind of a fun thing. Professional, I’ve had an epiphany, I’ve decided I’m going to write a book. I’ve embarked on that, I’ve jumped in full speed ahead. It’s basically Successful Leadership. I’ll update you more about that as it moves along. But I’m in the process of starting that now.

Roger Green (00:05:55): Personal, I’m not sure this is entirely a highlight, but it’s got its benefits, which is that I believe that my stepson and daughter-in-law and two year old granddaughter, the love of my life, are planning to move to Corpus Christi probably late this month, early next month. I kind of like Corpus, I like Texas. I kind of like the idea being two hours from San Antonio. Maybe Stephen can teach me how to surf on a boat after he teaches me about 21 Pilots.

Roger Green (00:06:20): Professionally, I think Episode 10 really is, like I said, when we started this, I don’t think we understood what we were stepping into. I’m not sure I would have volunteered, if I knew. But it’s a tremendous amount of fun, and I’m enjoying it more than I could have imagined. To some degree, it felt like the consolation prize for having EASL canceled, but I’m probably having more fun doing this than I would have had in London. That’s a good thing as well.

Roger Green (00:06:41): With that, let us step on. We don’t really have a question this week that I want to address. We had one question come up that we’ll address next week, but it starts with one person’s opinion on the answer to everything we’re going to answer today. I thought that would have been getting ahead of it. I want to go back to last week, last Friday was International NASH Day. Many of us listened or participated in some way, shape or form.

Roger Green (00:07:05): For those who listened or participated, I just want to know what you thought the best thing about the day or the event was. Mary, since I got to hear the panel that you spoke on, assuming you only spoke on one, if there was more, I missed the second one. Why don’t you tell us what you thought was the best thing about the day, first.

Mary Rinella (00:07:17): Unfortunately, I didn’t listen anything other than the session that I was involved in. But I do think it was wonderful to see a broad spectrum of people that represented different aspects, including patient perspective. I liked that, I really liked the attention that it gave the disease. I think it’s important, and I think it needs to continue. I’m sure it’ll build steam in the years ahead.

Roger Green (00:07:40): Okay, next.

Louise Campbell (00:07:40): I’ll go next. I thought it was thoughtful throughout the day. It was very thought provoking in various areas. There was a gentleman on from Nigeria talking about lack of access to anything, let alone non-invasive diagnostics, through different countries there and I thought there was some lovely stuff. There was a speaker from New York, he was talking very positively about the actual engagement of patients in non-invasive technology and how that was working for them with FibroScan, for example, in the fact that they can do it so frequently that the patients really get engaged and follow up.

Louise Campbell (00:08:17): I think that was one thing that we were talking about a couple of weeks ago. The general consensus that I got throughout all of the sessions, because I did actually go to them all, was how everybody was very much wanting collaboration throughout the world with early diagnostics for diabetes, cardiovascular disease, hypertension, and that early recognition through our colleagues in other specialties. But I thought the day was enjoyable to listen to and very nicely done.

Roger Green (00:08:47): Go ahead, Suneil.

Suneil Hosmane (00:08:47): I’m taking a step back. I remember where we were three years ago when we did the first one. I remember going to South Beach and what a crazy place to be going to talk and educating about NASH, right? I was probably the only person with NASH in the vicinity, I think of South Beach. But nevertheless, and then having all these different sessions, and now three years later, it’s expanded in scope. It’s expanded in terms of participation. It’s taking a life of its own from its early days from the NASH Education Program. I think it’s just pretty cool to see that as it’s continued.

Roger Green (00:09:18): I’ll tell you what, I was struck by… I caught about half the sessions, and you could hear the energy come into the conversation whenever people focused on patients, which I think is important and helpful, because at the end of the day, the patient is why we’re all here. You could… A little dry, a little dry, patient energy, energy, energy.

Roger Green (00:09:36): I was struck by the fella from Nigeria also, Louise, and the challenges that he faces and the people they’re facing, how different they are. It actually made me, not to be a downer, but it made me think of COVID where obviously Africa is going to have a horrible time. Same issues that he was talking about are going to apply there, double or triple fold. But in general, I thought the energy around patients of the day and the focus that people had around patients and the specifics of what we can help people do better with the disease was fantastic and really constructive. I left energized. I thought that was a good thing.

Roger Green (00:10:06): Bravo to GLI, bravo to Donna, Bravo to everyone else. Moving on to our main topic for today. We’ve got five people on panel all looking at the issue of diagnostics from different directions. Suneil as a commercial developer executive, current head of global diagnostics for GENFIT. Stephen as a researcher, but also as a guy who utilizes a tremendous amount of testing and widespread clinical trials, and separately, the person who identified and published the major paper on the coder reliability issues around biopsy.

Roger Green (00:10:35): Mary is someone who’s published a couple of really important papers on this subject and works in academia and does research. Louise as a patient advocate who administers a lot of FibroScans. Most… and advice along side them, mostly to underserved populations, and me as a forecaster and a strategist who looks at all this in terms of you can’t really develop a market or develop better protocols for treating a disease if you can’t figure out what you’re trying to do. That, I think has been a bit of a challenge here.

Roger Green (00:11:01): Two weeks ago, Suneil, Louise, Peter, and I spent about 45 minutes kicking this around, we came up with eight or nine major issues, which for the purposes of today’s conversation, I boil down into three themes, one of which came more from just me, one largely from Louise, one largely from Suneil. One came from Peter as well, I think. I want to mention each of the three questions, and then we’re going to go back one at a time, one of the panelists offered to take the lead and discussing it and then we’ll all kick around some questions, then we’ll move on to the next one.

Roger Green (00:11:29): My issue was the test we develop, can they teach us, can they teach researchers, practitioners, about the dynamics of progressive liver dysfunction so we can develop better treatment tools. You’ve got a disease that runs three to five decades over the course of somebody’s life, as Peter pointed out. The gold standard is a snapshot. We don’t know between Snapshot A and Snapshot B, let alone between year one and year 31, what are the moments at which severe things happen or things change? We know that there’s fluctuation, we know you can get better, you can get worse, the liver can regenerate, but we don’t really know how all that fits.

Roger Green (00:12:00): To the degree that we come up with tests that are dynamic, and enable us to figure out at what point do things cross a threshold, take a different direction, that will help us figure out who we have to treat and what points we have to treat most, that would be exceptionally helpful. That was point one.

Roger Green (00:12:13): Louise’s question, can tests guide better patient behavior? Can we develop tests and protocols around them so that care providers ideally, primary care can explain results to patients simply so the patient knows how to care for themselves better and can measure their own improvement? The fact that the liver is not only disease last forever, but it’s asymptomatic makes this more crucial. By the time you know you’re sick, you’re probably in really bad shape.

Roger Green (00:12:35): Then Suneil’s commercial perspective, how easily we tie these results to outcomes so that we can demonstrate the value not only of the test, but of the therapies that might become available that we were evaluating using those tests. How do we figure out what’s the best expenditure of resource and money and investment and all that to prove disease based on what we could track in line with the test? Those really were our three issues.

Roger Green (00:12:59): What I think we would like to do now is start with issue number one. I think Mary, this is the one that you volunteered to take if my notes are right. The issue of progressive liver dysfunction, which is what are the tests that we’re developing going to do to teach and improve on that? There are three questions. Question number one, on a zero to nine scale, where zero is not at all, one is minimal, and nine is the rather extreme, everything we’ll need to know, how far do you believe the test and development today will advance our knowledge on the progressive nature of liver dynamics, and how liver proceeds over time?

Mary Rinella (00:13:30): I think that’s a difficult question to answer, honestly. But I will say that if I think about the question in its totality and basically, what do the current tests tell us about the dynamics of liver function and the predictability of liver dysfunction over time, I would say that, we have a moderately good ability to do that. But ironically, despite the really interesting proprietary tests that are being developed, which I’m sure others, and we can comment on a little bit later, we keep coming back to just the clinical prediction roles, which essentially I take labs that we have available to us, and in some cases, patient characteristics.

Mary Rinella (00:14:08): What I think is the most important is actually to have increased education like we had with the NASH Day, and educate providers and patients to understand the risks of liver disease, and then to understand how to use these simple tests and when they need to worry. Something as absolutely simple as the AST to ALT ratio, for example, is something that providers can follow over time. The ratio starts to go up greater than 0.8, then you need to teach them to start to worry a little bit about that.

Mary Rinella (00:14:39): I think that as far as why that happens, I think it has a lot of different explanations, but there’s a biological reason why that happens, at least in part, and that’s because AST is cleared by the sinusoidal endothelial cells, and as fibrosis develops, that becomes less robust. That’s where you get a flip in that ratio.

Mary Rinella (00:14:56): Basically, teaching providers to look at that and understand the risks. I think that is an important way to tell liver function and liver dysfunction down the road. Other markers that I think probably Suneil will cover when he addresses question number three are things like, can we predict outcomes based on these tests? We can, based on the 4NFS, but we also have some really fascinating data with ELF, for example.

Roger Green (00:15:22): What we’ve got today, if we’re going to put on a zero to nine scale, where zero is really not at all what we need, one is minimally and nine is everything we need, where are we today?

Mary Rinella (00:15:30): I would say we’re at like a six. I think with reasonable comfort, we can diagnose advanced fibrosis, which then will give us a basic idea of outcomes. But even within that there’s a quite a lot of disparity between a one individual and another. I would say we’re at about a six.

Roger Green (00:15:49): If I were going to ask you this question three years from now, what do you think the next three years are likely to evolve in terms of the tests that are under development? What score would you give then?

Mary Rinella (00:15:57): I think it’s going to be a lot higher because I really think that one of the biggest issues and barriers we have with biomarker development is that we’re comparing it to a reference standard that is extremely flawed. The more confident we become in linking the diagnostic test to the outcome of interest, the less we’re going to really even care what the biopsy is, and we’re going to be really measuring it by its ability to predict outcome.

Mary Rinella (00:16:22): I think that once we have more data from LITMUS, from NIMBLE, and from other large trials, we’re going to probably forget a bit, we’re just going to forget about the biopsy, at least in the middle stages.

Roger Green (00:16:34): Okay. What you’re describing is a process of learning, as we get more large tests. Can you describe any either tests that are in development or talk a little more about those trials and specifically why they give you reason to feel optimistic, remembering that this is an audience that spans all the way from patients on over to investors and now commercial developers and doctors in the middle, just a little bit elaboration on what it is exactly events that make you feel that much more optimistic?

Mary Rinella (00:16:59): Sure. The one that’s probably the most exciting to me is ELF. If you look at, for example, the STELLAR-3 and STELLAR-4 trials, there were cut offs that came out that were able to give us predictability to, for example, progress from stage three to stage four. An ELF greater than 9.76 would predict progression of fibrosis. That’s really important from a drug development, treatment and regulatory perspective. Another threshold, I think 11.25 or so would predict adverse outcomes, which is also important. Now, the caveat with that, though, is that that population was pretty selected in the sense that those were patients already likely to have advanced fibrosis.

Mary Rinella (00:17:38): It’ll be interesting to see how well ELF fares in a more general population because that was a very enriched in advanced fibrosis. But that’s probably the most exciting. To me, I think PRO-C3 looks like it’s interesting but thus far, the performance characteristics are not far superior at all to just basic stuff, like FIB-4 for example, and transient elastography, of course.

Roger Green (00:18:02): If we look at this three to five years, what are we still going to find wanting here?

Mary Rinella (00:18:06): I think what we’ll have in three to five years is more data in larger populations. Ultimately, what you want to do is you want to identify people in the general population and primary care offices that are likely to experience an adverse liver-related event and are likely to benefit from a therapeutic intervention. Once we have more confidence that for example, ELF, which is under review by the FDA, will tell us useful information about predicting fibrosis progression or decompensation, then we’ll be able to manage people a lot more purposefully.

Roger Green (00:18:38): Okay, great. That’s a fantastic set of answers. Who would like to comment?

Stephen Harrison (00:18:42): I think Mary hit the nail on the head, we need to be able to provide simple tools to primary care providers so that they can basically have a conversation with the patients and begin to take the first steps to reversing or modifying or slowing down disease. It’s like anything else, if you don’t know what you’re dealing with, you don’t know how to address it.

Stephen Harrison (00:19:06): While there’s a lot of different biomarkers in development, I would say some are at different levels of providing data that’s helpful. Dr. Rinella alluded to ELF, which is a combination of three different wet or blood based biomarkers. It is a proprietary algorithm, if you will, that requires blood to be sent off for analysis. But there is a lot of data gaining steam behind its ability to detect progression to cirrhosis and even to decompensation as she alluded to, with the different cut-offs that were mentioned.

Stephen Harrison (00:19:38): Maybe more simply she alluded to AST and ALT ratio. I think for a primary care provider, and this gets into a little bit of question two that you’re going to ask me about, but I think it’s worth mentioning here, and that is primary care providers need something very simple that they can have a frank conversation with a patient, and say, look, if you don’t make a change in your lifestyle, you are headed down the wrong course of action.

Stephen Harrison (00:19:59): I think in AST, as it rises over time and reaches the level of ALT is something very simple for a primary care doctor to have a conversation with his patients over. Usually, there’s a set of historical data from which to glean kind of a historical review of those AST’s over time. If that doc can link an AST that’s risen over the past four to six years as he’s seen the patient, and there’s a setting of a diabetic or a fatty liver that’s historically known for that patient, then I think a conversation can be had.

Stephen Harrison (00:20:31): The future for this is it’s clearly going to get better. We’re going to refine our technique, we’re going to be able to provide more clarity around what I like to call the three different contexts of use. It’s diagnosing the type of liver disease it’s likely to progress. That is NASH with fibrosis from isolated steatosis. The second would be you put somebody on a drug, which we know are efficacious. therapeutic modalities are coming down the road. Some sooner than others, but we’re going to have treatment for this disease, likely starting this year, and it’ll only get better from there.

Stephen Harrison (00:21:03): But we have to have ways to assess the efficacy of the drug, and is the patient getting better, and how do we monitor that? That’s the second context of use. Then the third is long term patient outcomes. We’re really working hard on that goal as well. Ultimately, I think we’re going to be looking at combinations of wet biomarkers and imaging biomarkers.

Stephen Harrison (00:21:21): Dr. Rinella alluded to FibroScan at the end, I think that’s going to be something like that. If it’s not FibroScan, maybe it’s a portable handheld device that can connect to your phone, give you some idea of stiffness of the liver, if you don’t have access to a FibroScan. I think that’s coming here in the near future as well. But combining that with a wet biomarker, maybe something as simple as AST plus an imaging study, we’re definitely going to get better at it, as long as we can keep it simple and it’s readily available to a primary care provider.

Stephen Harrison (00:21:51): Maybe something that can be done before the patient is seen. Just like vital signs are done before the doctor goes in to see the patient. If we’re able to get something as simple as a FibroScan with a blood test, it gives us a number that we can link to a probability of having disease so that that primary care doc can walk in the clinic office and tell the patient, “Look, this is where you stand today.” Make treatment decisions based on that. Whether it’s referral to a specialist, or make lifestyle recommendations, I think is absolutely where we’re headed. We’re not there yet, but we’re making advances.

Mary Rinella (00:22:30): I want to make an additional comment. I do think it’s critically important to make things very, very simple. I think that awareness in general is improving, but even just… Primary care doctors are really focused on elevated liver chemistry tests, and that being the harbinger of bad disease. The issue, of course, is that as we know, 60% of people with advanced disease have normal liver chemistry tests. If we could shift their focus a little bit to think more about that AST and more about that ratio, and away from elevation versus non-elevation, I think we would identify people earlier. I get a ton of people that are already cirrhotic referred to me, who’ve been followed for 20 years of fatty liver.

Suneil Hosmane (00:23:11): That’s a lot of fantastic points. I think, taking a step back and looking at some of the data that we’ve generated internally on the biomarker side, I think that what we’ll begin to see as time goes on is there’s going to be unique and differentiated data that biomarkers provide. Forget about the specific biomarkers, just that category as compared to histology.

Suneil Hosmane (00:23:33): They’re not so much in competition, but they provide unique information. I’ll give you an example. There’s a number of patients and these are all patients that are within our clinical trials that have not been treated. They’re part of the placebo arm, natural history. That at baseline have very severe histological scores. You look at their biopsy and they look really bad. But biochemically and there’s various parameters for that we’re using — proprietary, non-proprietary — but they all converge at a very similar story where they’re biochemically mild.

Suneil Hosmane (00:24:03): Sometimes you see all combinations of these, you’ll see people who are histologically severe, biochemically severe, histologically severe, biochemically mild in all permutations. What we’ve seen, at least, is some of those patients you have severe histology, but mild biochemistry are less likely to progress, at least in the course of one year, one to two years versus where our data was built off of, as compared to people with biochemically severe and histologically severe criteria as baseline.

Suneil Hosmane (00:24:31): I think we’re going to see a different ah, scene in the way we’re going to bucket and sub-characterize these patients that will add clinical value, and it may provide justification for how we follow them moving forward. I think that’s where the field is going. But around the question around simplicity, ease of use, clarity, I completely agree with all the comments.

Suneil Hosmane (00:24:51): I think we should be headed as a field and I think we’re on our way. Having some level of consensus on how we intend to use various tools, whether they’re in isolation or in sequence. You know what specific cut-off or cut-offs, plural, makes sense or cut-off ranges makes sense for given application. Because you’ll see, across the spectrum, there’s a slightly different utility or use case from clinic to clinic. Everyone has their recipe. I think as that’s simplified, I think that will greatly ease the way in which we communicate about these tools and how they’re used by our colleagues.

Suneil Hosmane (00:25:27): Speaking about, just as an example of that, I think there’s a lot of great promise historically, and even out of STELLAR coming out of with the ELF data set and FibroScan datasets, for that matter. I think the one thing just to keep in mind is all of that data was aggregated and was split between an internal training validation set. Within that self-population, certain cut-offs were identified.

Suneil Hosmane (00:25:50): I think we’re all waiting to see as well as when you take all those cut-offs and you fix them in stone, and then you apply them to a completely independent population, maybe broader, to Dr. Rinella’s point, does it still have the same predictive power? My guess is it most likely will to some degree, let’s start to move in that direction and firm up some of these cut-offs associated with various tests.

Louise Campbell (00:26:13): I think from my point, there’s been a lot of excellent comments made. I think Dr. Rinella made the great observation that ELF is under FDA approval. It’s been available in the UK and Europe and it’s a highly sensitive test for cirrhosis. I think a lot of the biomarkers, again, we do know that a lot of patients, 60% more do have normal liver function tests. I think keeping it simple is relatively key. But liver disease isn’t just fibrosis. Most of these markers, ELF and most of the other scores do actually go on fibrosis. I think liver disease occurs before fibrosis. We know that fat and simple fat in the liver can increase your cardiovascular risk by two.

Louise Campbell (00:26:58): I think keeping things simple for GPs to be able to have that dialogue with patients in the surgery at the time and add wet markers to it are absolutely key. People do engage if they’ve got something to engage with at the time.

Louise Campbell (00:27:15): I think a lot of the algorithms we get excited by, but I don’t know very many patients who are that excited by the FIB-4 or ELF or the NASH fibrosis score and the predictive value. What they want to know is what can I do now, here, what little changes I can make. If you give a GP and primary care access to steatosis level on a FibroScan, and that’s only going to get better. CAT wasn’t available until four or five years ago, and we only had to deal with stiffness. I think now we get more and more accurate technology, we can add it to more and more wet markers. We will move, but we do need to keep the patients engaged and get them to start with small steps.

Louise Campbell (00:28:05): I think if you get a FibroScan or any non-invasive mechanism of telling somebody they’ve got a level of fat that can give them a heart condition, then they can change it. That conversation could be had, and more importantly, the primary care physician can monitor it every couple of months. No longer is the reply available of “Yes, doctor, I’ve lost weight, doctor or I’ve stopped drinking or I’ve changed my sugar habit and I don’t eat as much chocolate.” Because nobody could tell. The one thing that engages patients is you can turn around and say, “I can tell if you’ve given up those chocolates and sugary drinks.” Because you can see the composition change inside the liver, even if the weight doesn’t necessarily change for the patient.

Louise Campbell (00:28:49): I think keeping patients engaged, keeping the tests as simple as we can, but as accurate as we can. ELF is an excellent test and I would hope that the FDA approved that for you guys.

Roger Green (00:29:00): In some ways, it feels to me that we started on the first question, and then spent a bunch of time on the second one, which is about can we guide better patient behavior? Which is obviously pivotally important, particularly at the stage in the disease we’re in right now. I guess one of the things I’d like you guys to help me with a little bit that I didn’t hear or capture in the answer is, if you start to assume, look, I’ve used this metaphor on this podcast before, apologies.

Roger Green (00:29:28): Nixon said in 1969, we’re going to cure cancer pretty soon. We figured out there’s no such thing as cancer. There are a lot of different things that are all called cancer. I think it’s reasonably likely that what we’ll learn over time about liver disease is the same thing that Stephen has talked in the past about not really naming the disease until you figure out what all the elements are because every element is going to be its own disease.

Roger Green (00:29:46): One of the things I’m wondering is how… I think we’ve got the tools and I think you’ve all pointed this out, to do a better job of understanding how to educate, treat patients and to get patient management to a primary care level on a basic front. Do we have the tools that we’re going to need reasonably quickly and cleanly to start to sort out some of the issues around the “o-mics” of, the specifics of disease and why you would treat one patient one way versus another patient another way?

Roger Green (00:30:11): I guess that’s the question I’d like to ask and follow up. Folks jump in, and then we’ll move on, and then we’ll move on back to the patient behavior question.

Stephen Harrison (00:30:19): Roger, let me just chime in and just circle back hitting your second point about patient behavior. There’s the old joke that says, “How many psychologists or psychiatrists does it take to change a light bulb?” The answer is one, but the light bulb has to want to change. I think at the end of the day, patients have to want to change. Patients’ willingness to change is often predicated on what somebody tells them and if it’s powerful enough in the delivery.

Stephen Harrison (00:30:47): Another analogy would be when I tell a patient, they need a liver biopsy. When I tell a patient they need a liver biopsy, and one of my first year fellows tells the patient they need a liver biopsy, it’s amazing how many will agree to a liver biopsy after I explained it to them relative to the number of people that will accept a liver biopsy when my first year fellow explains it to them.

Stephen Harrison (00:31:10): It’s all in the delivery. If the physician isn’t armed with the tools they need to deliver an impactful message on what that patient needs to do, based on where they stand today in that physician’s mind with their underlying disease, then oftentimes, this falls on deaf ears.

Stephen Harrison (00:31:30): What we need to do, what people like myself and Dr. Rinella that see patients every day need to do is really be at the forefront of driving these non-invasive test towards those three contexts of use that I mentioned, so that we can look back towards our primary care providers and give them the tools they need to deliver that frontline message to the patients to basically force a change in lifestyle.

Stephen Harrison (00:31:58): When that doesn’t happen, then we move forward to pharmacotherapy, and we have additional tools to help guide response to that therapy. But I think it has to begin with something simple. And that also, just as much as we can develop a non-invasive test, there’s an education to the level of the physician that has to say, this is a serious disease, and these are the people you need to be focused on. That low hanging fruit that I’ve talked about before, would be a diabetic, an obese patient, a postmenopausal woman, age over 50, Hispanic ethnicity, these are all well-validated predictors of liver disease relative to NASH.

Stephen Harrison (00:32:42): Patient behavior is really going to be driven by that interaction with a provider, and the provider needs simple tools to help give them data to tell the patient where they stand in their liver disease. Louise mentioned FibroScan, it’s been mentioned several times. I think that’s a vitally important tool for its negative predictive value in telling people they don’t have disease, which is really just as important as telling people they do have disease.

Mary Rinella (00:33:08): Can I make an additional comment as well, Roger?

Roger Green (00:33:11): Please.

Mary Rinella (00:33:13): To emphasize a little bit more, Stephen’s last point, I think one of the things that providers need to do is very clearly explain, upfront before you do a FibroScan what the test can and cannot do. What you can say with confidence and what you can say with less certainty. The negative predictive value, I think, is where those tests really shine. I am definitely opposed to providers telling patients they have F2 disease based on a FibroScan reading. I spend a lot of time educating patients on different things that can increase liver stiffness, and what thresholds I’m going to use to push me towards biopsy and how I can use the CAP.

Mary Rinella (00:33:52): I do think it’s important to mention to the patients, it is great when you can do a CAP and see an improvement. But the problem with CAP is it’s really not a reliable marker for dynamic change. I try to preface all that before I do it so that the patients understand how to interpret the findings after they got them.

Roger Green (00:34:11): Excellent comments. Well, thanks, this has been, I think, really great 15, 20 minutes of discussion. Why don’t we move on to the next question? Can HCPs explain results to patients simply so that patients know how to care for themselves better, and can measure improvement specifically, given the asymptomatic nature of liver disease, which is you don’t know that you’ve got a problem until you really have a problem? Stephen, I think you said you were going to take this one. Why don’t you dive on in?

Stephen Harrison (00:34:35): I don’t know what more I can say, beyond some of the simple tests that we have right now that we can have a discussion with our patients about in clinic. I’ve got 20 patients coming in tomorrow to see me in clinic. The tools I’m going to use to help me are FibroScan, liver enzymes and platelet count, really more than anything else.

Stephen Harrison (00:34:56): If I’ve got an AST that’s close to the level of ALT, I’m concerned. If my platelet count is nearing 150, that gives me a cause for concern as well. Then the FibroScan, I use the CAP to tell me if the patient has fatty liver, I use the KPA above 8.5 to tell me that there may be a problem. Then I link that to the AST and the platelet count. Then all that tells me at that point is that I need to have a discussion with my patient about the probability that there is NASH and some degree of fibrosis, and that we need to pursue an additional workup that may simply be referral to a clinical trial setting, or it might be pushed to a liver biopsy. But it doesn’t also prevent me from having a discussion about how to manage that patient.

Stephen Harrison (00:35:42): We immediately pivot to the natural history: if we don’t do anything, what’s likely to happen over time. We talk about disease progression rates and there’s data on one stage every seven years of disease progression, obviously, that’s highly variable. Diabetes plays a huge role in the rapidity of disease progression. If they’re a diabetic, we have that additional conversation. But that allows me to then pivot to therapeutics and where we are today and a discussion on lifestyle modification and that this liver disease as long as they’re not cirrhotic, that it’s completely reversible, in most cases, and it really is predicated on their ability to lose weight and exercise. Four simple words, eat less, run more.

Stephen Harrison (00:36:28): There’s a lot more data that we talk about and precision around what types of diet and what types of exercise and how long, and that sort of thing. But I use those simple tools to guide that discussion. Just because I’m a hepatologist, seeing the more complicated patients, it doesn’t mean that I still don’t use very basic tools to help me in my management, and quite frankly, the same tools that a primary care doctor can use today. Will we we get better at it? Yeah, we’ll get better. We’ll have NIS4. I know Suneil is working hard on that. We’ll have ELF, we’ll have PRO-C3, we’ll have combinations of all those. We may even have Quentin Anstee’s ABC3D tool.

Stephen Harrison (00:37:09): But at the end of the day, it starts with a very basic and pragmatic evaluation of what everybody gets in their clinic: demographic information, basic set of labs. Then if you have access to a FibroScan today, that’s very helpful as well. Both for telling me they don’t have disease as well as telling me they might have a disease and what further work might be needed. That is a foundation and then we can build off that.

Roger Green (00:37:33): First let me go back to this the marketing researching question, which is on a zero to nine scale, where zero is not at all, one is minimal, and nine is everything we need to have, where are we never having what we need in order to support the patient better in the ways that we’re talking about, guiding better behavior and allowing HCPs to explain it to them?

Stephen Harrison (00:37:50): Well, if it’s simply a matter of diagnosing NAFLD, and I use NAFLD as an umbrella term, which is all encompassing, which quite frankly is all you need to have a discussion on lifestyle modification. Then I say we’re at nine. We can diagnose fatty liver, where we fall apart is diagnosing the specific subtypes of fatty liver, meaning NASH, NASH with fibrosis, NASH with advanced fibrosis. That’s where we struggle a bit to be very granular and specific as far as what degree of liver disease the patient has.

Stephen Harrison (00:38:24): But I would say on a scale of just having that discussion about, “You are at risk, you have a liver disease that’s very common, but it’s linked to metabolic risk factors,” we’re really good at that. I would put it at an eight or nine for sure.

Roger Green (00:38:41): Then where would you put us on the other one, the more specific, where are you further down the chain and how much risk are you at?

Stephen Harrison (00:38:47): I think that alludes to what Dr. Rinella said at the beginning, I would give it maybe… She said a six, I would say well, maybe more like five, we still have a ways to go. We’ve made some progress. We’ve alluded to a lot of biomarkers that are really beginning to show promise. But to Suneil’s point, they’ve really been tested in very unique patient populations and not necessarily across a more broad audience.

Stephen Harrison (00:39:10): We’ve made progress, I still think we have a ways to go. We’re facing a headwind because we’re comparing it to an imperfect gold standard. It’s very hard to really incrementally move that forward, but we’re making progress. I’d give it a five or a six, just where Mary said, maybe not quite as optimistic.

Roger Green (00:39:29): Okay, go on, folks.

Mary Rinella (00:39:31): I would agree with Stephen somewhat with respect to giving a nine to being able to have that conversation. I agree that you can do that. But the problem is, is that it doesn’t actually happen. I think that you or I or people that have a special interest in fatty liver disease, really feel comfortable talking about that and we can really inspire people and we often have support to help them lose weight. I have nutritionists in my fatty liver clinic, et cetera. But forget the primary care doctors, I mean, the other hepatologists that don’t deal with NASH, they don’t spend any time talking about that stuff.

Mary Rinella (00:40:08): I do think we really need to educate our own and the primary care people. It takes time, and you need to be comfortable with the topic. I think neither are true. I’m going to give it like a two.

Stephen Harrison (00:40:21): That’s the first time you’ve disagreed with me.

Mary Rinella (00:40:23): That’s not true, I disagree all the time.

Stephen Harrison (00:40:28): Just because you’re a terrific chef, a wonderful mother and a great liver doctor, doesn’t mean you can’t agree with me.

Mary Rinella (00:40:34): You’re almost always right.

Roger Green (00:40:36): That’s a good way to handle Stephen, you’re almost always right. I think that works. If we have the ability to be as high as an eight or nine if people have all the right tools, what should the priority be? I’m hearing we have a flood standard, we don’t have outcomes, we have biopsies which are flood standard. We don’t have frankly a lot of commercial investment behind this stuff right now, which is usually what moves us forward is commercial factors spend an awful lot of money educating communities. What’s the linchpin?

Louise Campbell (00:41:05): I am going to agree with Dr. Rinella on the, probably a two scale. That’s more because as you said, hepatologists, nurse specialists, people in the liver world, we’re comfortable with all those tools. But I think she’s right in the context that GPs, primary care don’t have access to some of these tools. I’ll go back to how she started the session this evening, Roger about your question, it’s about education, it’s about increasing the education to providers. It’s increasing the education to patients.

Louise Campbell (00:41:37): I think we’ve seen with International NASH Day that patients and advocates come together from around the world to push that. I think when I did some looking for that, I think if you take one of the major English diabetes sites, they recognized that 12.3 million people were at risk of diabetes. They also recognized that three out of five of those cases could be prevented. But there was not one mention of liver disease, or NAFLD and NASH on that page, there was only two references to NAFLD in the whole site, and this is one of the major sites for diabetic patients to access.

Louise Campbell (00:42:18): That was in comparison to 10 pages on the site in relation to heart disease. The education of other metabolic conditions to help locate what is a big cause of their condition has to improve in that education. I don’t think it’s any better within primary care, because we get patients all the time tell us that once they’re diagnosed with type two diabetes, all of the focus is on their diabetes, it’s not on their potential fatty liver, there is too little to non assessment of whether or not they could have cirrhosis, and yet they’re at a high risk.

Louise Campbell (00:42:56): That same site did a really good risk calculator, very similar to the British Liver Trust’s one, and on that site, 1.8 million people had completed that study. We missed 1.1 million people who would have had NAFLD out of that 1.8 million, but it wasn’t mentioned to them. More importantly, 292,000 to 351,000 of those patients would have been exposed to NASH.

Louise Campbell (00:43:25): Again, because that site didn’t mention it, those patients, they’re all missed opportunities. I think it is about the missed opportunities through lack of education, in primary care, in areas that don’t have the access to the equipment and the toys and the calculators that we have. I think without biomarkers showing it’s very, very difficult for them. I think education is key that, just to start looking in these populations to find these patients. I’m going to with Dr. Rinella, and also echo her comments at the very beginning, all about education.

Suneil Hosmane (00:44:03): Just to use some data or some insights that we’ve seen, at least on the clinical trial side, and from the sponsor side, I think it’s absolutely true that education and physician engagement and patient engagement for that matter are critical. You could give people all the right tools, but without the right context or without the right environment, it’s not going to succeed.

Suneil Hosmane (00:44:24): I’ll just give you a very brief example from our experience. When we’re really ramping up some of these trials back in 2015 and ’16, where there’s less availability, less understanding of some of these non-invasive technologies, you really saw a bi-modal distribution in terms of how effective a physician was, a clinical trial site was in enrolling patients into these studies.

Suneil Hosmane (00:44:48): You saw people who were very, very good that had very low screening failures, they’re identifying the right people, they were very prolific in their screening and identification, and then you had some that really had a hard time and you could tell they were doing a lot of effort and ultimately not identifying a lot of patients. We dove deep into this, and we said, “What’s the difference between these two groups? It’s clearly not purely effort.”

Suneil Hosmane (00:45:10): What we found was that… I don’t want to say causation, because causation is very different than correlation. But what we saw was in some of these clinical trial sites, they were being very prolific in their ability to identify the appropriate patient, advanced patients who have NASH and some level of fibrosis. They had access to multiple, non-invasive technologies. It’s not about saying that any one is better than the other, but just the use and the availability and the know how put them at an advantage.

Suneil Hosmane (00:45:39): I think you take that information, you also take some information about we know that there are clinical trials by investigators, and some of them are on the call, in fact, who have very good ability to leverage multiple tools, single tools to identify that patient population. The tools seem to be there and there’s better ones coming, as Dr. Harrison stated.

Suneil Hosmane (00:46:02): I think from a tool standpoint, we’re probably, this is just my opinion, we’re probably at a seven, and there’s always room for improvement, but without the right context, without understanding how to use it, and that engagement, I think the net effect will be a two or three like we were discussing. The data shows that that can move in the right direction. But that’s just something I think about when I hear about this type of conversation.

Stephen Harrison (00:46:26): Okay, I have to, for the record, say it’s tied two to two right now. Roger, you need to make a quick call.

Roger Green (00:46:32): I think I actually wind up with Mary and Louise on this, Stephen. I think we have the tools to do better, but we’re not communicating them very effectively. As a result, I’m mindful of a whole bunch of discussions that have run in the background through this podcast. One of them about exactly who understands how much about the ways liver is implicated in metabolic disease. You come back to the same things over and over again, which is, we’ve not done a really good job of helping people put the pieces together on where the liver fits in all this.

Roger Green (00:47:05): It’s the nature, I think of most processes except maybe philosophy and even some of that, that people tend to break things into discrete pieces as compared to see them holistically. What I take for a, the two in some ways, seven than others, is if there is a holistic picture, we’re not doing as good a job as amount of translating that to people.

Roger Green (00:47:23): I think that’s where I wind up as a tiebreaker. Sorry, if I disappointed you.

Stephen Harrison (00:47:26): No. I think at the end of the day, we’re seeing a lot of the same things. The tools are there. I think we all agree that there are simple tools that can help guide us. But if they’re not in the right hands, or they’re not explained in such a way that they can become powerful tools to be used on the front line, then it’s just going to sit there and not be utilized. Louise and Mary both say the same thing, in that regard. I think we’re all ultimately agreeing that it’s an education of the tools we have currently available that can take us to the next level.

Stephen Harrison (00:48:00): It’s not where we would like to be, ultimately. We can get better at it, but I think we have tools in which we can work with today. Part of it’s just the education of how to use those tools.

Roger Green (00:48:10): Well, and therein lies the catch-22 because the investment is about education and the education tends to come from people who are selling the medications or diagnostics, usually medications that enable improvement when people know what to do. In the absence of those medications, where the money is going to come from becomes an interesting question, but probably not one for today.

Roger Green (00:48:31): I’d like to shift to the third question for a few minutes. Suneil, how easily can we tie these results to outcomes so that we can demonstrate the value not only of the test, but the therapies might become available? First of all, the nine point scale, where are we at on that today, would you say?

Suneil Hosmane (00:48:44): I would say four out of nine? I think my answer is really premised on availability of that data. Not just availability of outcomes data, but availability of paired data. To that, I mean data in which we have clinical samples, we have blood or serum or some matrix, and then we also have biopsy results, clinical outcomes data, so we can begin to marry these datasets together and make these very, very important associations that then take us, I would say, to the very next level, which is, instead of just clearly continuing to validate against a reference standard that has some variability, all due, to move towards association with something that’s more robust and more meaningful in terms of clinical outcomes.

Suneil Hosmane (00:49:32): Now, I think with that said, and I’m not talking about it, particularly with our technology, or what we’ve done but just as a blanket statement, this is where blood-based biomarkers and circulating biomarker technology has an advantage. Because the one thing that you can do with blood-based biomarkers is if you have banked samples, and these things exist in various diseases all around the world, you can begin to do these type of retrospective analyses. You can take new innovations today and you can apply them to existing samples and dig out of the past.

Suneil Hosmane (00:50:03): The one thing that is harder to do, much harder to do if the technology was not built to do this, it takes things like imaging data where a lot of the core raw data is lost. What we see when we’re looking at an image is a processed image. A lot of the fundamental physics that went behind acquiring that image is gone. It’s harder to innovate in certain technology, unless you’re prospectively collecting a ton of data and takes a long time to collect outcomes-based data.

Suneil Hosmane (00:50:32): I think from a blood based biomarker standpoint, I think we can move a lot quicker. It’s still slow, because you need to not only show this association or correlation, but you need to show it to the points raised throughout the entire podcast. We have to do it against multiple data sets, because you want to make sure that this association that you have is robust, and it’s not an artifact of one particular study design.

Suneil Hosmane (00:50:57): It can happen in different speeds. I think blood-based biomarker’s a little bit advanced in that category compared to imaging, but they really add very synergistic information about the patient. It’s not about competition, they’re providing unique value.

Roger Green (00:51:12): Okay, that’s a great answer. Suneil, one of the things that has been striking me throughout the last hour of this conversation, you’ve touched on it a bit indirectly, is all the ways that having biopses as the reference standard holds us back. Dr. Rinella literally started on that back at the beginning about the challenges having a flood standard.

Roger Green (00:51:34): But it strikes me that one of the reasons we’ve got to do so much work with so many different kinds of datasets and prove this thing so many different ways is because the target that we’re starting by shooting at is such a messy target. It’s an asymptomatic disease, we don’t really know what we have until late. The gold standard tool for measuring it, doesn’t measure very well. By the way, it measures inconsistently depending who’s looking at it. I’m wondering how much of the value of the multiple data sets is simply allowing, A, us to create some outcomes and B, for all those data sets to coalesce around a more consistent and more tangible way of measuring what we’re trying to achieve and what the challenges are for the patient? Does that make sense as a question? If it doesn’t, I’ll try it again. If it does, yes or no?

Mary Rinella (00:52:18): Yeah, I’ll jump in. I definitely agree with that. I think that rather than perseverating about how closely we can link a biomarker to a liver biopsy, I think we need to really pivot and just start looking at our outcomes. That’s really what matters at the end of the day. We can make assumptions that somebody is getting better and we may be altering their outcome, even by looking at their ALT. If you see a drop in 17 units, then you’re going to see a change in histology. If you have an improvement in histology, you’ll probably improve or reduce adverse liver-related outcomes.

Mary Rinella (00:52:53): We don’t know that of course, but you can make that presumption. But I think that the issue with histology is Stephen has beautifully dissected that. My argument has always been, if you’ve got a drug that really, really works, that a little bit comes out in the wash. But unfortunately, right now we’re dealing with, we need to use drugs in combination. At the end of the end of the day, single agents are going to really struggle, I think, with this disease, for the most part. Anyway, circuitous, but I agree, we have to focus on outcomes as our target.

Suneil Hosmane (00:53:26): I completely agree. I think we haven’t largely been in disagreement I think in this podcast, but obviously coming at it from different angles, which is interesting in and of its own right. There’s multiple angles to this. I think you’re correct, there’s more data, as there’s more aggregate data coming from different places, that increases the chances of seeing signal over noise. I think that’s a true statement. The faster we can do that, and the faster we can look at that, compared to outcomes, the faster the field can move.

Suneil Hosmane (00:53:54): With that said, I think the other thing that we should be doing, which I don’t know if we are completely doing as a field, is really taking a hard look at the data in different ways. It’s certainly… I’ll just give you one example. It’s just a hypothesis that I’ve had, and maybe there’s an answer to it. But you look at histology and you look at these multiple features. By the way, there’s thousands if not millions of features on that slide where we usually only talk about four of them. But then on that slide, for example, when we say inflammation, we’re counting nuclei and that’s perfectly fine.

Suneil Hosmane (00:54:28): However, the inflammation process, the inflammatory process is both helpful and can also be deleterious as well. It all depends on the context. We know that the immune system is very important for regeneration. It’s also important for clearing infections, disease, et cetera. When you see an inflammation scoring, is that pro- inflammatory, is that anti-inflammatory? Just as an example. That’s going to modulate how you characterize the biomarkers being well-classified or not. It could just be that we don’t completely understand the biology.

Suneil Hosmane (00:55:05): I think another element behind the scenes is we’re digging deeper into what all of this means and peeling back the onion, discovering deeper science. I think that’s going to elevate the field as well, that that’s going to take longer, because you’ve seen how that’s had an impact on other fields, like oncology and other spaces.

Mary Rinella (00:55:24): That’s where AI is going to help. AI is incredible at detecting, even picking up tumors better than people in some studies. I think we’re going to learn a lot from AI, to the points that you raised about what the characteristics of a liver biopsy are that might indicate more progressive or improving inflammation or disease.

Roger Green (00:55:45): Ironically, the question I didn’t start the session with was an AI question. Go ahead, Stephen.

Stephen Harrison (00:55:49): No, I was just going to say, I agree completely with both of those points. Maybe my last point to that would be what’s really catapulted this and I think will be a boost to helping us quickly find some of these answers out non-invasively is what we’ve discovered this past year with liver biopsy. We’ve known about it, but really the studies that we’ve done looking at the heterogeneity between readings, the inter- and intra-observer variability with liver biopsy, I think it’s really pressed everybody studying this, to lean in more, to find the answers to non-invasive technologies quicker.

Stephen Harrison (00:56:33): Because we’re not slowing down drug development, we’re really moving forward with disease awareness, I think through International NASH day and other avenues. The one thing that’s kind of lagging behind a little bit now is that non-invasive technology. I think really, we’ve just sat by and said, well, liver biopsy is it. Let us just deal with this imperfect gold standard.

Stephen Harrison (00:56:55): I think with some of that data coming out now, that just really hits home the fact that we’ve got to get better at finding ways to determine disease severity and monitor people on drugs and look at long term outcomes. I think because of that 2020 is a pivotal year in pressing forward with our non-invasive testing and our ability to hone in on those different contexts of use.

Roger Green (00:57:21): Stephen, that’s, I think, a fantastic thought and summary. Louise, I’m going to ask if you have anything to add, and then we’re going to roll to the last question.

Louise Campbell (00:57:29): The only thing I’m going to add is I think it’s about also defining the outcomes. Outcomes from diagnostic technology and finding fibrosis, and the accuracy that we can get with all of these tests is all well and good. But actually, the outcomes for patients are finding the disease earlier, so that I don’t get liver cancer. It’s about early location, it is about more than 25% of liver disease being diagnosed by a primary practice. Patients not finding out in casualty at an average age of 50, that they’ve got first presentation decompensated cirrhosis.

Louise Campbell (00:58:06): Our outcomes would be different to the outcomes of biomarkers, liver biopsies. It’s about we need to find the disease earlier so that we can stop this rising cancer, so that we can stop this cardiovascular, so our outcomes will be slightly different to just diagnosing diagnostics, I suppose. If they don’t bring us earlier diagnosis, then what outcomes are we actually aiming for?

Roger Green (00:58:32): Look, I think that’s an excellent point and an excellent place to… We’ve gone full circle three or four times in this discussion in different ways. I think it’s been fascinating. Stephen, wrapping up with you because I know you got to jump in a minute. Final question, what’s the one thing you heard or realized today that surprised you most?

Stephen Harrison (00:58:47): Well, it’s clearly that Mary disagreed with me. That just broke my heart and left me despondent. However, I’m going to get past it. I think Suneil said it, we’re all coming at it from different angles and saying a lot of the same things, that really education is paramount to this. We have some tools out there that could be helpful. I think we all get the sense that, and Mary and I see it in clinic all the time that even the simple tools we have aren’t being utilized. A great example of that is, I saw a patient last week that had been to multiple different specialists for an evaluation of a low platelet count.

Stephen Harrison (00:59:28): A lot of workup was done by a hematologist because that’s where the patient went first from the primary care doctor was, low platelet count, this has got to be a bone marrow issue, go see the hematologist. Really, there was all the signs there that this was progressive liver disease. It’s a simple education thing and that can go a long way. Do we have to improve? Sure we do. Our testing needs to get better, but we have some education to do first and foremost.

Stephen Harrison (00:59:58): I think that is what I took away from this is that reinforcement across the patient perspective, Suneil’s perspective as well as Dr. Rinella’s perspective.

Roger Green (01:00:09): Stephen, thanks a lot. We’ll see you next week. Whoever wants to go next jump on in, what surprised you?

Mary Rinella (01:00:14): Well, I think what surprised me is a little bit what Stephen just said. I am going to end this with agreeing with Stephen. I think that all of us come from such different perspectives and we all identified very similar issues. Now, I think what we need to do is put this a bit more into action and come up, distill down to very simple message that we can disseminate to the frontline that see patients with liver disease. That’s not hepatology, but it should include of course, a hepatology.

Roger Green (01:00:45): Suneil or Louise, take your pick.

Louise Campbell (01:00:46): I think the thing that surprised me the most was that we all agreed that we’ve got some good, if not great diagnostics, but actually we are failing to get the message across in most other areas. I think agreeing with Dr. Rinella that education does have to carry on.

Roger Green (01:01:04): Suneil?

Suneil Hosmane (01:01:06): I’m going to buck the trend. I think everyone said what I want to say. I will say that it was very interesting. It felt really good to hear about International NASH Day living strong, very strong programs, and still kind of galvanizing. There’s still a lot of interest in the community, which I think is fantastic.

Roger Green (01:01:24): Let me see if I can buck two trends at once. What I’m struck by is two things, which is, at the very basic level that we’re talking about, education exists, tools exist, tests exist, we could get 80% of the way to where we need to be if we could capture it, bottle it and get it up the front line, as Mary points out. There are going to be some rather interesting resources and challenges in doing that, I think, because where the resources tend to come from, to do that are the last 20% of what we don’t have yet, or what we haven’t figured out how to do.

Roger Green (01:01:53): I think the challenge going forward will be to figure out how to take what we already know, what we talked about today, that I think the commercial communities have undervalued and give it the value necessary to engender the energy to drive the education that we need to have. That’s a long way of saying it, but I think that’s the point. It’s there. Now the question is how to get it executed, and to motivate people to have the resources in place. That I think was my surprise, that wasn’t where I thought I’d wind up today, or we would.

Roger Green (01:02:22): I want to thank Dr. Rinella, for joining us and Suneil, for coming back and Louise for joining us at the last moment when Peter wasn’t able to make it. It’s been great having you here, and Stephen, always. Next week, there are a couple of possible topics for us to talk about, we might bring back some of our colleagues for the first couple of weeks to talk about why there isn’t a lot of merger and acquisition activity in this space. We might wind up going and visiting the issue of AI, which is I think, something we don’t spend time on yet that we really want to, and we may step further into really what will help patients in situations where they’re in underserved environments to get them what they need?

Roger Green (01:02:59): All those subjects will happen relatively soon. I want to thank everybody for being part of what we’ve done today. I want to thank those of you who are out there listening as we keep growing this podcast and getting more and more people excited. Everybody, have a great week, stay safe and surf on, we’ll be back. Bye, bye now.

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