This transcript accompanies the accredited CME program led by Zobair Younossi, MD, and Tony Villiotti.

1. NASH Patient POV
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Patient POV: New and Emerging Approaches in the Management of Non-Alcoholic
Steatohepatitis
Module 1: Introduction & Background
Dr. Zobair Younossi: Hello, I'm Zobair Younossi. I'm the Chairman of Department of
Medicine at the Inova Fairfax Medical Campus. It's my pleasure to welcome you to this
program on new and emerging approaches in the management of non-alcoholic
steatohepatitis. I've been in the field of fatty liver disease for the past three decades,
and I'm also joined and want to welcome Tony Villiotti, who is a patient advocate,
Founder and Board Chair for the NASH kNOWledge. And I'll turn this over to Tony so that
he can actually share his experience with all of us. Go ahead please, Tony.
Tony Villiotti: Thank you. I was a NASH patient. I was diagnosed with fatty liver, which
progressed to NASH, which progressed to cirrhosis then liver cancer. I've experienced
the full gamut of the experience. I had a transplant then about five and a half years
ago, and as a result of my experience with liver disease and a transplant, I thought I
had an obligation to help others from following in my footsteps. So we founded NASH
kNOWledge. Our goal is to increase awareness and provide education regarding non-
alcoholic liver disease.
Dr. Younossi: Wonderful. Thanks, Tony. And I think this is an incredibly important
perspective, not only from Tony's perspective as a patient, but also his efforts to
increase awareness about this disease, which is probably one of the most important
challenges in this field.
These are our disclosures. You can see the learning objective. We will cover both sort of
the burden of disease as well as diagnostic and treatment that are currently available
or those that are going to come down the pipe.
So let me actually give you some background about this disease. This is a very common
disease. When you look at the global prevalence of non-alcoholic fatty liver disease,
which is also now called metabolic-associated steatotic liver disease or MASLD, that
prevalence is about 30% globally. The highest prevalence is in the Middle East and
South America, but the rest of the world, a quarter of the population of each region of
the world, have NAFLD. NASH, which is the progressive form of fatty liver disease, is
about the prevalence and the general population, you just have to estimate that, the
prevalence about 5.5% or so, again, very high prevalence rates in the Middle East,
North Africa, as well as in Latin America.
Now, when you look at the rates of NAFLD over time and look at the studies that were
published in the past three decades, you see that the actual prevalence between 2016
and 2019 studies that published during this period of time is about 38%. So it's even
higher than 30%. One group of patients that have been at risk for fatty liver disease are
those who have type 2 diabetes. This is a meta-analysis that we did a few years ago
looking at the prevalence of NAFLD among diabetics. That prevalence was about 55%.
This is 2016 data. Currently, we're finishing up another meta-analysis, and it seems that

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the total global prevalence of NAFLD among type 2 diabetics is around 60% or more
than 60% or so. About a third of these patients and even up to half of these patients,
the diabetes with fatty liver disease, if you biopsy them, they have steatohepatitis,
which is a progressive form of fatty liver disease.
Now, of course, patients with NAFLD are at risk for mortality. This is also from meta-
analysis that was recently published, and you can look at the most common cause of
mortality. These patients die of cardiovascular mortality, of extrahepatic cancers—
these are cancers from the gastric cancer or stomach cancer, pancreatic cancer—but
also they die of liver mortality. In fact, these are the three top causes of death and
account for over 66% of death among these patients.
Let's go to the first poll question and answer is actually D. When you look at patients
with Type 2 diabetes and NAFLD, not only the prevalence of NAFLD is high, they're at
higher risk of mortality. And I'll show some data. And the other part of this is that if you
actually do a liver biopsy and show that patients have stage two or higher, they're also
at higher risk of mortality.
Tony, did you have any of these components of metabolic syndrome over the years
and were you diabetic? What was the situation for you?
Tony: I was a Type 2 diabetic and I was also overweight. So I had two other risk factors,
and at the time I did not realize that that made me at risk for NASH.
Dr. Younossi: Did you have any symptoms, Tony, during this period of time that you were
sort of slowly developing fatty liver disease?
Tony: I had no symptoms at all. In hindsight, maybe there was a little bit of fatigue,
which I attributed to getting older, could have been a symptom of fatty liver disease.
Dr. Younossi: Very important point. Yes. Coming back to what we were just talking
about is that if you look at the top bars, can you have advanced fibrosis and the
number of components of metabolic syndrome? If you're diabetic, especially if you
have diabetes and visceral obesity, you see that the percentage of patients that had
advanced fibrosis increases with increasing number of metabolic syndrome
components like type 2 diabetes and obesity. At the bottom, this is not a study we
published using NHANES' database. This is actually looking at a population of patients
with fatty liver disease and metabolic conditions. As you go from the top to bottom,
when you have no metabolic syndrome, you're in this green bar in terms of mortality,
survival time. And if you have all the component of metabolic syndrome, you're in this
sort of a black line in the bottom. So you see that the more components of metabolic
syndrome you have, the higher the chance of mortality.
The second point that I was making, it was about stage of fibrosis. And this is something
that we initially published in 2012, and then the subsequent meta-analysis, this is the
most recent meta-analysis showing that if once you get to stage two or higher—being
stage one is very little fibrosis, stage two is sort of middle of the road, stage three and

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four are called advanced fibrosis or advanced scaring of the liver—then aall-cause
mortality and liver-related mortality goes up. And the bottom, it's actually the opposite.
So of course, it's from a placebo arm or the arm of a study that did not work. The drug
doesn't work. But some patients had spontaneous regression of fibrosis and you can see
that if you actually have spontaneous regression of fibrosis, the chance of liver events,
that means having decompensated liver disease or mortality, goes down.
So these are the two important predictors of adverse outcome. Now, what Tony said,
which is extremely important, is that symptoms of non-acholic fatty liver disease are very
nonspecific. One thing that's actually quite important is that although it's not entirely, at
least in my experience not entirely asymptomatic, patients have quite a bit of fatigue or
have fatigue, and they just attribute that to their sort of life and aging. So fatigue is
common in patients with fatty liver disease, but other symptoms are not that common.
And this is really part of the problem that this disease can go on in a way that is not very
clearly symptomatic to patients.
Module 2: Diagnosis
Dr. Zobair Younossi: So now let's see, look at what diagnostic tests are available to us. So
let's just go to the poll question number two, and I'll just go into the correct answer,
which is D. Fib-4, as we will just review, is a simple test that's used as the initial step for risk
stratification. And as I'll show you, it does actually do quite well in terms of excluding
those patients that have advanced fibrosis and cirrhosis. But there's some caveats, and
we'll discuss those, in terms of impact of age. Tony, did you have any liver enzyme tests
done before your diagnosis? Or any other tests, like CAT scan, or ultrasound or anything
else that was a part of your evaluation, before you got to diagnosis of liver cancer and
cirrhosis?
Tony Villiotti: Yeah, the first test I had done were the liver enzymes, and that's what
preceded my fatty liver diagnosis. The doctor told me my enzymes were elevated, and
he thought I had a fatty liver. As far as a NASH diagnosis, there's a nine-year period
between my fatty liver diagnosis and my NASH and cirrhosis diagnosis. And during that
period, they continued to do the liver enzyme test, but nothing beyond that. It wasn't
until doctors suspected I had NASH and cirrhosis, so I kind of went from zero to 60. At
that point, I was referred to the hepatologist. And she did ultrasounds and MRIs, to
monitor the progression of my disease, from that point forward.
Dr. Younossi: Were you diagnosed with liver cancer at that time, or did it take a bit of
time after that?
Tony: It took about two years after my cirrhosis diagnosis, to be diagnosed with liver
cancer. I have to say, once I had liver cancer, that's when the symptoms really started
to set in.
Dr. Younossi: Yeah, absolutely. I think the two things that's important is that most patients
in NASH who develop liver cancer, they have underlying cirrhosis or advanced fibrosis.

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But I think it's also important to note that there is a group of patients with NASH, without
cirrhosis, that can develop liver cancer as well. That's actually very peculiar about this
disease. Because you don't necessarily screen patients who just have NASH without
cirrhosis, for a liver cancer. But once you have, of course, established diagnosis of
cirrhosis, then these patients should go every six months of ultrasound, and potentially
sometimes blood testing to screen for liver cancer. And we'll talk about some of the
other issues, in terms of management.
This is another typical patient, 65-year-old man, who was referred by his family physician
for evaluation of elevated liver enzyme. Remember, this is a very common scenario in
pathology practices, where you get patients for evaluation of elevated liver enzyme.
And you will find out that the liver enzymes are usually mild, for a very long period of
time, and in this case was 20 years. And you look at the risk of the labs, the AST was
higher than the ALP, so that actually tells you, if you remember, the AST being higher
than the ALP is also a reflection of "suspicion" for alcoholic liver disease. But people
don't realize that this is also a situation where cirrhosis can be suspected, even in the
absence of alcohol.
The rest of the labs are okay. Even platelet count is fine. Hemoglobin A1c is 6.2. An
ultrasound had shown fatty liver. And you see the medication list over here, suggestive
of multiple components of metabolic syndrome, type 2 diabetes, hypertension, GERD.
BMI is 35. The patient drinks one beer per day, and that may not be excessive, for most
people who are not obese. But in the context of fatty liver disease, that probably is too
much alcohol. And if you look at the waist circumference, so not only this patient has
obesity by BMI, but also waist circumference is enlarged, so he has visceral obesity. And
as I reviewed, the ultrasound just showed fatty liver. And of course, you have to exclude
other liver tests. And I'll just tell you that the ultimate markers is smooth muscle antibody
and ANA are mildly positive. This is not uncommon in fatty liver disease. It doesn't mean
that the patient has autoimmune hepatitis. The iron studies can be slightly elevated,
and sometimes, you're stuck. You have to do a hemochromatosis test here. Most of
these patients with fatty liver disease can have high ferritin, which is an indication of
insulin resistance, that iron overload. But we'll have to actually make sure there is no iron
overload if we do additional studies.
Let's now review some of the biomarkers. Liver biopsy, as I mentioned, was the way to
diagnose the steatohepatitis in the past. But regular imaging, like ultrasound, or MRI, or
even CAT scan can just show fat. But they're not very good, in terms of distinguishing
steatohepatitis or stage of fibrosis. So, to develop tests that are going to focus on stage
of fibrosis, there are a number of tests that have been developed. The three that are
the top, Fib-4, APRI, and NAFLD fibrosis score are non-invasive tests that can use clinical
data. As you can see on the right, these are very easy tests, easy parameters to get.
The one that's used most commonly is Fib-4, so that's what we do. There is a serum test,
called Enhanced Liver Fibrosis Test, that's now approved for prognosis of non-alcoholic
fatty liver disease, and it's a send-out test, and it has pretty good performance for
patients with non-alcoholic fatty liver disease for stage of fibrosis.

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Going into the next slide, we'll show you the other noninvasive tests, which are
radiologic, and really here, we're looking at tests that measure stiffness of the liver. The
one at the top, which is transient elastography is pretty good. It gives you both liver
stiffness, as well as CAP, which is a measure of hepatic fat. It has good performance, in
terms of excluding cirrhosis, so it has good performance for exclusion of cirrhosis. But
positive predictive value or the ability to include cirrhosis is not that good. When you go
at the bottom, you have MR elastography, which also can tell you if the patient has
fibrosis. It's more accurate, but probably less available and more expensive. So a
Fibroscan or a trans elastography cutoff of 8 and higher suggests some degree of
fibrosis. And for trans elastography, that's about 3.63 kPa.
Now, just let me share some data, on the left, about Fib-4. So when you look at Fib-4,
this is a launch student study of over 20,000 patients. And when you look at the patients
in the bottom graph, those who have high risk, so this is a Fib-4 of more than 2.67, or low
risk is a Fib-4 of less than 1.3, and you can see those who have high risk, they are at high
risk of adverse outcome, in the follow-up in the solid lines. But even though those that
are actually has an increase in their progression from one to another, then they also
have more progressive liver disease versus those who have a decrease, and after 12
months of change, a changing in their Fib-4. A change over time also could indicate
potential better outcome, if it's decreasing, and maybe worse outcome, it's increasing.
On the right side, this is 894 patients with biopsy proven NAFLD in NASH, with transient
elastography, two trans elastography. And they were categorized in terms of those who
are progressors versus non-progressors. So those patients who had evidence of
progression by trans elastography had more liver events, as documented here by
development of that decompensation HCC or a MELD score that's higher.
With that, I'm just going to quickly review that these algorithms have become part of
the approaches by a number of different societies, the GI societies, endocrine societies
that have adopted some of these algorithms, to use Fib-4, and followed up by
additional tests.
This is one that actually was published and developed by the American Association for
Clinical Endocrinology, in 2022. What you do is to first look at patient’s risk profile, so if
they’re pre-diabetic or diabetic, or they have obesity and two other cardiometabolic
risk factors, or they have steatosis, by imaging or elevated liver enzyme. These are the
patients that have high likelihood of having fatty liver disease. Then first test is to do a
Fib-4 test. If it's less than 1.3, then of course, low risk for adverse outcome. These are the
patients that will be managed by their primary care team. If they have high risk,
meaning a Fib-4 of 2.67. And of course, you can confirm this with either an ELF test or a
trans elastography. So they can have a trans elastography of more than 12 kPa, and an
ELF test of 9.8 or higher, then they can be managed by hepatologists, because they
tend to have higher risk in NAFLD. If you're intermediate risk, this is really when you want
to do elastography or ELF testing and sort of categorize these patients into high risk or
low risk.

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The most recent guideline that was published is the AASLD guideline. And on the left, is
basically where primary care and non-hepatology care is. Again, looking at risks of type
2 diabetes, etc., doing the primary risk assessment with Fib-4 again. Low risk, again,
followed by primary care physicians. And if they're diabetic, you repeat Fib-4 every one
to two years. If they are not diabetic, or don't have other cardiometabolic rescue,
repeat Fib-4 every two to three years.
Now, for those who have more than 1.3, you can actually consider a transient
elastography. And if it's less than 7.7 for ELF, and less than eight by trans elastography,
then they go to primary care. If there are more than that, then they can go to the
hepatology care referred for that. And you can consider another test, like MRE, or MR
elastography, and subcategorize them. And some of these patients, despite these non-
invasive tests, a very small proportion of these patients may still not be able to be
categorized as high risk or low risk. And yes, at that point, depending on patient's
situation, you can consider liver biopsy, and then liver biopsy. It remains a gold
standard, in terms of stage of fibrosis. And of course, those patients with advanced
fibrosis can be managed for their risk factors.
So for this patient, three non-invasive tests, Fib-4, APRI and NAFLD fibrosis score that
were done and they were all in intermediate ranges. And if you look at table, it just tells
you that these patients have intermediate sort of stage.
Tony, did you have any of these tests done, before seeing your hepatologist?
Tony: Actually, I did not. I had none of the tests, and actually never even had a liver
biopsy done.
Dr. Younossi: Yeah. And I think this is part of Tony's entity, that is the NASH knowledge
that he is promoting, and all of us, is to promote that these non-invasive tests exist, and
very easy to calculate. The Fib-4 test is on the internet. All you have to do is to plug in
the numbers you can get, and you get pretty important information. For example, you
can say that you're not going to have advanced fibrosis. And that may be 80% of
patients that will fall into that category. Then, you can focus on that 20%. So that
awareness that Tony is trying to accomplish, and we're trying to accomplish, especially
to us primary care, to adopt these algorithms would be very important.
Now of course, the trans elastography is a good test, and would be good secondary
test. The problem, of course, is that it's not always available. Sometimes, you have to go
to GI or subspecialty hepatology if primary care is not available. But it's a good test,
and it's available. You certainly can actually use it. Now, alternative of course, would
be enhanced level fibrosis or ELF test. That's a send-out test. It should be available. And
if you are of the labs, that you have access to it.
So again, as Tony and ourselves go into sort of promoting awareness about this disease,
and the primary care and endocrinology practices, as well as for patients, where we
are promoting algorithms that identify those patients who could be at advanced risk for
adverse outcomes.

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So here is the Fibroscan. Fibroscan showed a 16 kPa. Now, according to the sort of
cutoffs we use, 16 kPa suggests advanced fibrosis. And the patient wanted to know
exactly what type of biopsy finding he has. And especially, if you remember at the
beginning, we showed that iron studies were high. So sometimes, you're stuck because
you want to exclude not only NASH, but also iron overload. And of course, this biopsy
showed steatohepatitis, with bridging fibrosis. And the iron stain showed minimal iron
staining. So this patient does not have iron overload, but does have bridging fibrosis,
which is considered advanced fibrosis.
Do you want to add anything, Tony, in terms of your experience, and the labs you have
from your journey with this disease?
Tony: The other thing I would like to add, one of the things we do at NASH kNOWledge
is that we run a support group for liver patients. And there's an extremely high level of
interest in what's going on in a non-invasive testing space. Patients are very interested in
finding ways not only to diagnose the disease, to monitor the progression of the
disease. So there's a very high level of interest in the patient community, in non-invasive
testing,
Dr. Younossi: And that's wonderful, Tony. Tony, are you doing your support group
virtually through Zoom, or are you doing it in person, or both?
Tony: Yeah, we do it virtually, through Zoom. It initially was planned to be an in-person
group, but it was to start actually the day they closed everything down for COVID. So
that kind of forced us into plan B, and it's worked out very well. We have over 200
people who are on a mailing list for the support group, and we have participants from
about 25 different states, who are members of the group.
Dr. Younossi: That's wonderful. And I will hope that every site, including ours, would be
very interested to know maybe the details of the support group, and how we can
actually engage with our patients more and more. So thanks, Tony, for all the things
that you're doing here.
Module 3: Treatment
Dr. Zobair Younossi: So let's take a couple of seconds so that people can actually
answer. We will go ahead into the answer, which is basically A, which means that all
patients should actually have a serious attempt with lifestyle modification, and this
should be delivered by a multidisciplinary team. We'll review that.
So let me just review some of the data, and I'll tell you the caveats about the lifestyle
modification. So when you look at the data, and this is the Vilar-Gomez study at the
top. The bottom line of this study, which is a relatively small study of 293 patients with
NASH, and lifestyle change was with weight loss over 52 weeks, you'll see that, in order
to improve fibrosis, you have to lose about 10% of body weight, which means that this
occurred in only about 10% of patients.

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The type of diet may or may not be important. At the bottom, you see the intermittent
diet versus low-carb, high-fat diet. You see that the amount of weight was actually
weight loss, probably was the same. So both actually diet was affected. In my
experience, Mediterranean diet probably will have the best outcome. Here, of course,
the outcome was liver fat improvement by MRS.
Now, there are other things that people can do, which is not only changing diet, but
also alcohol intake. Exercise, both aerobic and anaerobic exercise would be important
in this context and will improve potential outcome. And that's actually summarized in
this top study, which is randomized clinical trial that patients were either randomized a
low-fat diet with physical activity or without physical activity, or Mediterranean diet with
physical activity, with or without. This was moderate physical activity. And as you can
see, the best outcome was actually achieved... Again, when you're looking at visceral
adiposity or intrahepatic fat, these are the outcomes. The best for all of these
interventions was basically Mediterranean diet with moderate physical activity. So
moderate physical activity can actually enhance the impact of the lifestyle
modification.
There are other things that's going to be important. One important aspect is that you
can't just tell the patient, "Go ahead and lose weight or exercise." That's going to have
a low likelihood of success. Lifestyle modification has to be considered like any other
prescription. So you have to provide the means and monitor patients, and of course
that requires dieticians and exercise specialists, sometimes behavioral health. It may not
always be easy to deliver all of that in a sort of under one sitting, but I think all attempts
must be made to do this in a multidisciplinary setting, even if you do this through virtual
care where you're connecting patients.
Now, for some patients where they meet the criteria for bariatric surgery, bariatric
surgery can be very effective for treatment of NASH. If patients lose weight, this is the
French cohort, you'll see that the weight loss actually led to the resolution of
steatohepatitis and improvement of fibrosis in lots of these patients. And they were
sustained with up to five years of follow-up here. So it could be a good way of
approaching these patients, but of course you have to be a candidate for bariatric
endoscopy.
Now, a couple of things that's important is that patients who have advanced fibrosis,
especially those who have decompensated cirrhosis, they will have high risk of mortality
from bariatric surgery. Second is that some patients post-bariatric surgery can develop
alcohol use disorder, so it may be an issue. So you have to follow these patients to
make sure that they don't replace fatty liver from metabolic conditions with alcohol.
Let's look at some medication. This is data on pioglitazone, suggesting that, when you
look at conclusive study, some aspects of steatohepatitis improve in patients who are
actually both diabetic and pre-diabetic patients who received pioglitazone at 30
milligrams per day. Now, there is also meta-analysis that confirms this. First we have to
worry a little bit in patients who have some cardiac abnormality and will have some
complication for pioglitazone. And of course, there is also some data suggesting that

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you may gain some weight. But that gain of weight is actually moving fat from visceral
area to maybe distribute it more of a peripheral area, so it may not be a major issue.
Another family of drugs that would be really interesting and important are the GLP-1
agonists. This is the semaglutide data, phase 2 clinical trial. And as you can see in this
phase 2 clinical trial, this was daily dose of semaglutide. There was body weight
change, hemoglobin A1C actually improved. And when you look at liver biopsy,
steatohepatitis resolved in a large number of patients without worsening of fibrosis, and
that was highly significant as compared to placebo. Unfortunately, the fibrosis
improvement was not met. This may have been due to the study design, but this drug
was actually effective in all subgroup analysis. Core side effects of the GLP-1s are GI
side effects, and now this drug is going through phase 3 clinical trial assessment.
Let's look at some other potential regimens, and I'm just going to show you the sort of
cartoon of the pathogenesis, which is a multi-head hypothesis where you have fat that
ultimately is coupled with a second step of either oxidative stress or dysbiosis that
ultimately can cause activation of stellate cells and causing scarring of the liver or
fibrosis. So patients can have one or multiple components of this pathway involved.
Some of the drugs address obesity, and they're all listed here. Others can actually
address the endocrinopathy that may be common in patient with fatty liver disease,
lipotoxicity and mitochondrial dysfunction, especially endoplasmic reticulum stress
could also play a role here. Of course, inflammation, metabolic pathways could be a
pathway that could be targeted by a number of drugs. A number of antifibrotic drugs
have been used, and unfortunately, they have not worked so far.
Let's review some of these studies. This is the study on a pan-PPAR agonist called
lanifibranor, phase 2 clinical trial suggesting that when you look at biopsy, there was
improvement of steatohepatitis and fibrosis. And on the table at the top, number of
non-invasive tests also improved with lanifibranor. Looking at transient elastography,
there was also an improvement of fat, which was measured here by CAP. So, again,
this drug is undergoing phase 3 clinical trial.
Another family of drugs is thyroid receptor-beta agonist, resmetirom, and this is a
metabolic drug. This is a Phase III clinical trial that was presented earlier this year. And as
you can see, there are two doses of resmetirom with placebo. And the primary
outcome again is NASH resolution, and it was met by both doses of resmetirom, as well
as improvement of fibrosis by one stage. This was met as well. And there were some
adverse events that are listed here, but in general, the drug is well tolerated, and this
drug is being considered for approval, obviously.
The other drug that I wanted to at least mention here is the FXR agonist, obeticholic
acid. Here was an 18-month. This is an outcome study. The initial study was published in
Lancet, I was the first author, showing that it actually improved fibrosis but not really
steatohepatitis. An expanded analysis was done that showed that improvement
happened in both steatohepatitis and fibrosis. This was actually, all the biopsies were re-
read by a panel of pathologists, and again, the primary endpoint was met.
Unfortunately, there was some side effects that's important to mention. Pruritus was one
of them, but most cases of pruritus was mild, and it could be easily managed. Some of

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these patients did have dyslipidemia, again, could be managed with statins. There
were at least, the regulatory bodies considered some cases of hepatotoxicity, and that
led to the fact that the agency required an outcome study. But the company has
decided to close the study, so, unfortunately, this drug is not going to go for full
approval for treatment of NASH.
Finally, a drug that I just wanted to mention to you would be the family of drugs that we
will see more and more of. These are dual agonists, and this is GLP-1/glucagon receptor
co-agonist. And when you look at the clinical trial, which is a phase 2 clinical trial, they
compared the drug to semaglutide. But please remember that the dose that they're
using here is not the dose that's being tested for NASH. NASH is 2.4 milligram sub-Q on a
weekly basis. This is the 1 milligram which is for diabetes. But regardless, you'll see that
both of these two drugs had significant improvement of a number of non-invasive tests,
although the dual agonist had better outcome with the dose of 1 milligram of
semaglutide. So the GLP-1s or GLP-1/glucagon receptor co-agonist, or other
combination co-agonist with GLP-1s could potentially be an important regimen for
treatment of NASH.
So let me just conclude, and then we'll get into a little bit more discussion that NASH
complications that I've shown have been growing. NASH and type 2 diabetes,
especially those who have stage 2 fibrosis are especially at high risk. Tony said there are
a number of non-invasive tests that are available that should be used for risk
stratification of these patients. Raising awareness in the primary care setting or in
patients’ sort of group through the support groups that Tony is actually talking about is
going to be very important. Management requires multidisciplinary team. Of course, we
always have to consider lifestyle intervention in a serious way, but there are other
medical treatment, even bariatric treatment that could be available. As I've shown
you, there are going to be a number of drugs that are coming down the pike,
combination regimens, a regimen that could be used as an induction, and then
maintain that improvement that you get for some patients may be the future. And the
box on the right just shows that the component of the multidisciplinary team that
ultimately can be developed, if not in person, but at least virtually.
So I'm going to stop here, but I'd like to get, Tony, your insight about, once you had the
diagnosis of fat liver disease, what was sort of the treatment regimen that your doctors
were suggesting? Anything at all?
Tony Villiotti: Well, he said I should lose weight. The issue, I've probably been told to lose
weight at every doctor's appointment of my adult life. So that didn't really set off any
warning bells. And the other thing, and this goes back to your point about the
multidisciplinary team, he didn't tell me how to lose weight, and he didn't connect me
with nutrition experts that may have helped me to craft a lifestyle plan. That would've
been very helpful. The other thing that I was not told, I really didn't know I was at risk for
developing cirrhosis. The fatty liver diagnosis did not carry any urgency in my mind. If I
had been told I was at risk for cirrhosis, I think I'd have taken the lifestyle changes and so
forth much more seriously and might have even been able to avoid cirrhosis and the
transplant that I ended up with.

11. NASH Patient POV
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Dr. Rubin: Very, very important points. I think, first of all, the knowledge has to increase
among all stakeholders that this is a progressive disease. As I've shown, it's the number-
one cause of cirrhosis in the United States. In fact, our data this year that we are
presenting shows that NASH is the number-one indication for liver transplant. If you go
for a liver transplant, for liver counts, it's a number one. It's number two for all liver
transplant in the United States, so it's got to be an understanding that you have fatty
liver disease, it cannot be dismissed, it's not a "benign disease". This is a potentially
progressive disease that can go to liver cancer and cirrhosis. And the second point you
made, Tony, is extremely important, is that you cannot just tell the patient, "Go ahead
and lose weight." That's just not going to work. So if you want to do this, then you have
to at least put together, at least if you cannot do it as a multidisciplinary team that
could come together, make those connections available with nutritionists and with
exercise specialists, and treat this like any other disease that will require sort of a care
pathway. That would be important.
So thank you all for joining us, and hopefully this session will have an impact on
educational activity of patient care in NASH that you're involved with. In four weeks,
you'll receive a follow-up survey. Please see if you are able to implement these
changes, and feel free to send us an email. Before I close this, Tony, I want to thank you
for joining here, and I want to give you the last word to see if you want to add anything
else to what I've already said.
Tony: Well, thank you. I appreciate the opportunity to participate in this discussion. I
guess my last word would be, even though we're very hopeful of getting a drug
approved by the FDA in the near future, having that drug is not going to reduce the
importance of making nutrition changes. It won't be a case where you can take a pill
and sit on a couch and eat pizza and drink beer. The medical solution will only be a
part of the solution, and I think we need to keep that in mind.
Dr. Younossi: Very well said. Thank you, Tony. And thanks, everyone, for joining us.