(logo whooshing) (gentle music) - So, just to talk about the basic outline of what
I'll be covering tonight, I will be talking about NAFLD basics, and I will tell you what I mean by NAFLD. NAFLD diagnosis and staging,
complications of NAFLD, and finally, management of NAFLD. So, the first question is really what is this thing called NAFLD? Non-alcoholic fatty liver disease. So this is a disease that occurs when fat is deposited in the liver without other causes of
fatty liver identified, and I'll go into some of the
specifics a little bit later. But before I do that, I do
wanna kind of define the terms, because I'm gonna be throwing
out some of these terms throughout the course of the talk, and I want you to understand what all these different acronyms mean. So, we really think of NAFLD, or as some say, NAFL D,
as our umbrella term. And underneath this umbrella falls NAFL, non-alcoholic fatty liver, which means fat in the
liver without significant inflammation or liver cell damage. And NASH, which stands for
non-alcoholic steatohepatitis. And this means that
there's fat in the liver with a characteristic
pattern of inflammation, as well as liver cell damage. Some people will use these
terms interchangeably, but that's actually incorrect. It is important to kind of understand that these are technically two different sub-conditions under
the umbrella of NAFLD. Now, why is that important? We know for sure that NASH can contribute to liver fibrosis or scar. And just thinking about
what does that really mean? When you cut yourself, you get a scar, and what's really happening
in the liver is that as there's inflammation
sparked by the fat, the liver really tries to repair itself, and as the liver is
trying to repair itself, it does lay down scar tissue. So in people who have NASH, they can develop this liver scar, and about 20 to 30% of patients will actually go on to develop cirrhosis. And I think sometimes when
people hear the term cirrhosis, you think, well, I'm not a drinker, what are you talking about? Well, that's exactly why
the title of this disease is non-alcoholic fatty liver disease, or non-alcoholic steatohepatitis. We know that, but any
chronic liver disease can cause cirrhosis. So cirrhosis does not equal alcohol, cirrhosis means extensive
scarring of the liver, and any chronic liver
disease can cause that. We also know that people
who have NASH and liver scar can develop hepatocellular
carcinoma, or HCC. And this is primary cancer of the liver. So what we used to think was
that patients who had NAFL would always stay in this category, and we thought that they were at very low or really even zero risk
of developing cirrhosis. But in the past several years, we have actually seen that
there have been studies demonstrating that patients
who were in this so-called benign category have actually
progressed on to cirrhosis. We're not exactly sure why that is. One of the thoughts is, are these patients actually
flipping back and forth in between NAFL and NASH? Or is it that maybe we
misclassified the patients when they were first diagnosed and put them incorrectly
into this low risk category. Or it could be that this actually does lead directly to cirrhosis. There aren't that many high
quality long term studies including large groups of
patients, so this is really something that we are
still learning about. So now, with NAFLD, we have
to think who is at risk? So there's something called the
so-called metabolic syndrome which you may or may not know about, and the metabolic syndrome
includes several conditions, including obesity, particularly people who have more central
obesity, or if you think about body fat distribution, more
in an apple type distribution rather than a pear, meaning that the fat tends to accumulate in
the middle of the abdomen and the legs are skinny, versus the pears where the fat kind of really
deposits below the waist. So just think about those two fruits. The apples are the ones
who are at greater risk of metabolic syndrome and fatty liver. Patients with high blood sugar
or diabetes or pre-diabetes, high blood pressure or hypertension, and high cholesterol and or
low good cholesterol, the HDL. So really, all of these
conditions are seen commonly in people who have fatty liver disease. And we tend to think
of fatty liver as being kind of the liver manifestation
of the metabolic syndrome. We think that it's probably what obesity and some predisposition to
develop these liver diseases is what these patients have in common, rather than one of these
things kind of causing the fatty liver, but it's
one of those diseases where it's kind of a vicious cycle, where the diabetes may
affect the fatty liver, fatty liver may lead to diabetes. Obesity also increases risk of diabetes, increases the risk of fatty liver, so, the thought is maybe there
is one common risk factor for all of these conditions. There are other risk
factors which have emerged as kind of the non-classic
risk factors for fatty liver. Some of them do include
Hispanic ethnicity, which may in part be related
to some genetic factors that have been identified. Polycystic ovarian syndrome, which is a syndrome seen in younger women and they can actually have cystic ovaries, but they also have elevated
levels of male hormones such as testosterone and DHEA. And a lot of these patients
have other metabolic syndrome risk factors such as obesity
and diabetes or pre-diabetes. Patients with HIV also
are at increased risk for fatty liver disease, and it's thought that it may
be related to the disease or the medications or an
interaction between the two things. Sleep apnea is also very common in patients with fatty liver. And hypothyroidism is common as well, though hyperthyroidism
is common in general. So, I know the title of my
talk was this silent epidemic, and any time you have a
talk about fatty liver, you've gotta bring up the obesity prevalence maps from the CDC. And I think this is gonna
cycle through once or twice, really showing you that
the prevalence of obesity in the US, as I think you're all aware, has really increased
significantly over time. And you'll see as these
slides cycle through, that more and more states in the US have this higher obesity prevalence in the range of 30 to 35% or more. In California, we have a
little bit less obesity than the rest of the country, but again, obesity, very
prevalent, very common, and there is that strong link
with fatty liver disease. So looking at this map, it
kind of makes sense to me why we are seeing this
epidemic of fatty liver starting to explode. So with that, I want you
just to think for a moment after seeing those maps and seeing that such a large proportion of
the US population is obese, and I've mentioned the link already, what do you think the
prevalence is of NAFLD in the general US population? And what do you think the
prevalence is of NASH, this more aggressive subtype
of NAFLD in the US population? If you wanna yell out a number, great, if you wanna keep it to
yourself, that's fine, but I'll let you just
kind of sit with that and think about it for a minute. 35 and 10, those are
really excellent guesses. Did you look at my slides beforehand? So yeah, pretty darn close. So there's a range, 16 to 29% of the US population has NAFLD. And this really mirrors the
prevalence of obesity in the US. Whereas NASH, the more aggressive subtype, probably about 5% of the US population. And if you think about
this on a population scale and thinking about how many
people are actually in the US, that is a huge number of patients. So this is a really huge
public health problem, and it's something that people really do need to be aware of. And then thinking about
other patients subgroups, in patients who are
obese, about two thirds will have fatty liver. Almost all patients
who are being evaluated for bariatric or weight loss surgery, probably about somewhere
between 50 and 75% of patients with diabetes have fatty liver. And the more aggressive subtype NASH, of those patients who have
NAFLD, 10 to 30% have NASH. And 20% of obese adults have NASH as well. So again, big, big problem. So, how would you know if you have NAFLD? I mention again, it's a silent epidemic. Well, it's because many patients will have no symptoms at
all, up to 77%, in fact. If they do have symptoms,
they may not be very helpful in terms of guiding us as physicians or other healthcare providers to the fact that fatty liver may be present. Fatigue is very, very common, present in 50 to 75% of
patients with fatty liver, but the problem is, is that fatigue is a common feature of
many different diseases. So if someone says they're fatigued, that unfortunately doesn't help me, because there's a huge, long
list of things that can cause fatigue, and fatty liver is one of them. The other reason why fatigue
is an important feature of fatty liver is that
sleep apnea is very common in our patients with fatty liver as well, and that can certainly
contribute to daytime fatigue. If symptoms are present,
right-sided abdominal pain may be present, and that's because that's where your liver is. And we think that the reason
why patients will have pain in the setting of fatty liver
is that as the fat deposits, it can actually stretch out the lining or the capsule of the liver. And that's really where the
nerves are in the liver, they're not on the inside,
they're really on the outside, sensing problems with the
external parts of the liver. But what I always tell my patients is that just because you have pain and you have an established
diagnosis of fatty liver, that does not necessarily mean that your liver disease is getting worse. It doesn't mean that because you have pain that your liver is sicker than someone who doesn't have pain. Pain is something I think we really still don't understand very well. But for, again, for whatever reason, some patients with fatty
liver will have the pain, in part related to the stretch
of the capsule of the liver. Other things that might
make you suspicious of having fatty liver is the
presence of risk factors, and I've already mentioned
the high prevalence of fatty liver in patients who
are obese or have diabetes. Lab testing may also clue you
or your health care providers into the fact that fatty
liver may be present, with the liver enzymes,
specifically ALT and AST being elevated, and usually, ALT will be higher than the AST. One thing to be aware of is that as hepatologists, as liver specialists, we kind of use a different
range for normal liver enzymes than your local lab might. And I'll explain why that
is, it's not that we're just crazy and setting a really low threshold, it's that when the labs actually develop what their normal values
are, they derive that from the general population that's actually getting their blood drawn. Now, I've told you about a
third of the US population has fatty liver disease, so if they're deriving their normals from this abnormal population, you can see how that can
really skew the normal values to being higher than
they probably should be. A normal ALT, just so you know, for a woman should be less than 20 to 25, and for a man should
be less than 30 to 35. And I've seen some local labs say that an ALT of 60 is normal, and that's absolutely not true. For a woman that's close to three times upper limit of normal. So, other things that can
clue you into the presence of fatty liver is the
appearance of fat on ultrasound, MRI, or CT scan. And this is also how a lot of patients will come to our attention,
that they complain, I have pain on my right
side, appropriately, their primary care doctor
will get an imaging study, and then they see, oh,
the liver looks like it has fat in it, and that's
what usually initiates a referral over to my clinic. So, you would think because
fatty liver is so common, I haven't told you about
the consequences yet, but just thinking that
there are populations that are likely to have fatty
liver, should we screen? If you look at the guidelines from the US, which is the American Association for the Study of Liver Disease, ASLD, they don't recommend screening. The recommendations are a little bit vague in that they suggest a
high level of suspicion in high risk patients. They kind of stop short of saying that we should be screening these patients. And part of this is related to cost. If you're thinking about screening the at risk US population,
which is probably, again, about a third of the US population, that can be quite costly. And if you don't yet have
treatments that are cost effective in reducing serious liver-related problems or liver-related death, then the screening may not make sense, though I suspect in the coming
years that this may change. The European guidelines, this
is a European Association for the Study of Liver, they're a little bit more prescriptive. They say you should screen
all patients with obesity or metabolic syndrome by
checking liver enzymes and ultrasound. I think this is a little bit overkill. I think we really should be focusing on our highest risk patients,
which tend to be patients with diabetes, because they are the ones that are most likely to
have advanced liver disease in the setting of fatty liver. I think it's premature to say
we should screen everybody who is obese and everybody that has a metabolic syndrome problems
such as high blood pressure, high cholesterol, but
again, that may change. So, if your health care provider does diagnose you with
suspected fatty liver, should you see a liver specialist? And you would think as a liver specialist, I would say, well, absolutely,
I want more patients. Let me tell you, my clinics are exploding. It's very hard to get people in, and we're really trying to figure out how we can see the highest risk patients. But why should you see a liver
specialist if you have NAFLD? Well, one reason is to
make an accurate diagnosis. We wanna make sure that
there are no other forms of liver disease, because
we've seen plenty of patients that were billed as fatty liver because it was kind of the right scenario. They were obese, they had diabetes, high blood pressure, high cholesterol, you probably have fatty liver. Most of the time you'll be correct, but maybe about 10, 15% of
the time you're gonna be wrong and you're gonna miss
other liver diseases. We've diagnosed autoimmune
hepatitis, viral hepatitis, all other chronic liver
diseases in patients with you just have fatty liver. So, we still think it's
important to rule out or eliminate other
causes of liver disease. The other reason to see someone like me is that we want to determine
the subtype of NAFLD you have. NAFL versus NASH, and I will tell you a little bit later why that's important. We also want to evaluate you
for liver scar or fibrosis. Liver biopsy may be needed, though it's not needed in all patients, and I will talk about how I decide whether to biopsy someone or not. The other reason to see a liver specialist is for monitoring. If you are in that higher
risk category of NASH or if you already have
pre-existing liver scar, we wanna make sure that there
are no signs of worsening. And particularly if you have
progressed to cirrhosis, you do warrant additional monitoring. We want to monitor blood work to make sure there are no signs of liver dysfunction. We wanna see you periodically to make sure you're not showing signs
of liver dysfunction. And because patients who
have cirrhosis are at risk for liver cancer, we also want to be doing some sort of abdominal imaging
study like an ultrasound, CT scan, or MRI, to
screen for liver cancer. So, in definitely the
higher risk patients, we absolutely want to be
seeing these patients, it's just a challenge in figuring out who really, really needs to see us and who can kind of live in primary care. So how is NAFLD diagnosed? So, several things. We first wanna make sure
that there's actually fat in the liver. If there's no fat and if
there was never any fat, it's probably not fatty liver, and I will say the one exception
is if you have cirrhosis. Because as the liver disease progresses, the fat goes away, but the
scar can still increase. But in general, we wanna
see that there has been fat, either on ultrasound, MRI, or biopsy. CAT scan or CT scan may not be good enough to eliminate the possibility of liver fat unless there's a lot of fat. So, just because there's no fat on CT scan doesn't mean it's not there. As I mentioned, it's really important that we eliminate other
causes of liver disease, and this is usually
through an extensive panel of blood tests. It's important to make a
kind of clean diagnosis of NAFLD, that patients are drinking fewer than two drinks per day. And that they're not taking
medications known to cause fatty liver, and two very
common ones are prednisone, which is used to treat a lot
of autoimmune conditions, allergies, as well as tamoxifen, which is a medication
to prevent recurrence of breast cancer. Now, what I will say is that
it is not always this clean. We like to say that NAFLD is
this diagnosis of exclusion, that we've eliminated everything else, but we see that NAFLD coexists
with other liver disease. We've seen this in our
patients who have hepatitis B. About a quarter of our
own patients in our clinic have hepatitis B and fatty liver. Patients who've had hepatitis
C were cured of the virus, and then they went on
to develop fatty liver. And we've had patients who
have autoimmune hepatitis, other chronic liver diseases
who also have fatty liver. So even though, yes, we do wanna eliminate other causes of liver disease,
it doesn't necessarily mean that fatty liver isn't also there. And then we also have patients
who drink a little bit more than this, but maybe not
quite to the threshold where we would say we think they have alcohol-associated liver disease. And that's a really interesting topic in terms of alcohol and fatty liver, and I have a little bit
of information about that at the very end of the talk. But again, I think this is just in the cleanest sense of the word, if you're drinking more than this, we can't technically say
that it's just NAFLD. And then finally, a word
about the medications. Yes, we know that prednisone and tamoxifen can certainly cause fatty liver, but again, in the right scenario, if you have someone
who is obese, diabetic, high blood pressure, high cholesterol, and they also happen to be on prednisone, it's hard to say, well, it's
definitely the prednisone. Maybe the prednisone is making it worse, but it's really hard to kind of pin all of the fatty liver
just on the prednisone, so, not always such a clean diagnosis. So, now, what about liver biopsy? Now, I do not biopsy every
patient that comes to see me, and that's something that
patients always worry about. They show up and say, "Oh
no, I don't want you to do "a biopsy," or, "I thought I
was gonna get a biopsy today." And a lot of times I don't. But the reason why I do biopsy is to make sure I'm
classifying NAFLD accurately. I wanna know, do they have NASH or NAFL? I want to determine
fibrosis or scar stage, and I want to eliminate other
causes of liver disease. Because the blood test
to look for other causes of liver disease are very
good, but they're not perfect. Some of the blood tests
to look for things like autoimmune hepatitis can also
be abnormal in fatty liver. So sometimes we just need
that biopsy to say, okay, do you have just fatty liver, do you just have autoimmune
hepatitis, or do you have both? What I'm trying to target
when I choose patients to do biopsy on is I'm
trying to biopsy patients who have NASH or are likely
to have advanced fibrosis. And that's because those are
our higher risk patients. Ideally, I don't want to
be biopsying the patients who are at low risk. So we do look at liver biopsy
really as being the most reliable means for excluding
other causes of liver disease or coexisting liver disease,
and we still call it our gold standard for
diagnosis and staging, but I kind of think it's a
little bit of a tarnished gold standard, I'm still
a big, big believer in liver biopsy, but I recognize
that there are problems. So, sampling error is a problem. I don't know if anyone
here has had a liver biopsy or know someone that's had it, but what we see is that a tiny
little worm-like structure, a tiny little piece of liver
comes out of this big thing. And we assume that what we're seeing in that tiny little
sliver is representative of what's going on in the entire liver. Now, if the liver biopsy
is an adequate specimen, if it's long enough, if it has enough samplings of portions of the
liver called portal tracks, then we feel reasonably
confident that the liver biopsy is telling us what's
going on in the liver. But the problem is
sometimes the liver diseases can be patchy. So, maybe we picked an area
that had a little bit more or a little bit less fibrosis, or maybe when I biopsied you,
you had a little bit less inflammation than you did when you had the blood drawn three months ago. The other issue is that
when we do the biopsy through someone's side,
which is our usual approach, we're going through sometimes
several centimeters of fat, meaning that our needle is only so long, so it can be hard to get
a really good specimen. And if the liver does
have significant scar, like cirrhosis in particular, the specimen may not come
out in a nice long piece, it may come out fragmented. And that affects our
ability to accurately assess how much liver scar there is. There's also the risk of complications. So, discomfort is very common. Thankfully, more serious complications like significant bleeding or
death are not very common, but those risks are there. The other issue is the
expense of the biopsy. So, what we're paying for is my time, the pathologist's time, the radiologist to do the ultrasound, the
cost of the ultrasound, the procedure area, nurse's time, patient takes the day off from work, their ride takes the day off from work. And think about kind of amplifying that across a third of the US population, and then we'd run into even more problems with financing health care
than we have right now. So, for all of these reasons, this is why we cannot biopsy every single patient with suspected fatty liver. So thankfully, we do have
other tools at our disposal. So this test, Fibroscan, is the brand name for a test called transient elastography. So this is an ultrasound-based test. And what you're seeing here
is a patient lying flat, and the tech is using this probe that kind of looks like
an ultrasound-based probe, this is kind of an
ultrasound-based modality. And what's happening is
that the probe is placed to a similar spot on the right side as to where we usually take our biopsies. And then what happens is
that these shear waves are sent through the liver,
usually about 10 times, and we're trying to measure
how stiff is the liver? The stiffer the liver,
the more likely it is that there is more liver scar. The pro of this test is that it's fast, there's several pros, it's
fast, relatively cheap, it's non-invasive, it only
requires three hours of fasting, and it doesn't require
someone having a ride home. So, very many pros of this test. But there are things that can
produce inaccurate results. Obesity, NASH, well, that's a problem. 'Cause these are the people
we're doing this test on, and I just told you it's a great test, we may get inaccurate results sometimes. If there's a lot of liver inflammation, if the ALT is greater than 100, if there are other significant
abnormalities of liver tests, if there's a lot of fat in the liver, this can lead to an
overestimation of liver scar. Recent alcohol use, we think
within maybe 24 to 48 hours, that can impact the results and maybe overestimate liver scar. And potentially, Hispanic ethnicity, and we found this in our multicenter study looking at patients with fatty liver, and the thought was that
on average, these patients were a little bit shorter than
some of our other patients. So maybe the distance between the ribs may be a little bit
smaller, and that may affect the accuracy or the validity of the test. This has not necessarily been
replicated in other studies, but a lot of other studies
don't have high proportions of Hispanic patients in them. The other issue is that
the Fibroscan does require adequate experience to
produce reliable results. So, not every center is necessarily going to have a Fibroscan. So, this is not a test that is routinely done in primary care, and that's really because
there's not the expertise to learn how to do this and do it well, 'cause you really need to
do it over and over and over again to get really good at it. In our clinic, we have
several staff members, mostly our LVN and medical assistants who are doing this procedure,
and they've all done at least hundreds at this
point, and they're excellent. But when we first start
seeing someone do this test, we get more invalid results. So again, there is that learning curve. So, if I have a patient who
wants to get a Fibroscan close to home, if I don't
necessarily know that center and understand what their
experience is with it, I may say, well, you can do it, but I'm not sure if I'm
going to trust the results. Whereas our center, or
another high volume transplant or tertiary center, I know
they're doing these things all the time and I'm more
likely to trust the result. So why is it that an accurate diagnosis and staging are so important? Well, I will tell you, We really think of these
as two different diseases, as I had alluded to. So I mentioned that both NASH and NAFL can cause liver fibrosis,
and this is really just showing you the spectrum
of liver fibrosis or scar, which we stage on a scale of zero to four, where zero is none and four is cirrhosis. And we think that it
takes about seven years for patients with NASH to
go from one fibrosis stage to the next, meaning that
it may take about 28 years to go from zero to cirrhosis. Now on the other hand,
if a patient has NAFL, the less aggressive form, we
think it takes twice as long to go from one stage to another, equating to about 56 years
from zero to cirrhosis. Now, this may be the reason
why initially we thought that NAFL could not progress to cirrhosis. If your disease starts
when you're 40 or 50, most patients are not
going to live long enough to develop cirrhosis and then signs of liver dysfunction or liver cancer. So, the other thing to
know is that the prognosis of NAFL does differ
according to fibrosis stage. So in the patients who
just have steatosis, and this is just a fancy word for fat, if they have just fat,
we think that up to 40% may progress to NASH with or without mild degrees of fibrosis. And of these patients, five to 10% may progress to advanced
or stage three fibrosis. And then here's this really,
I think, meaningless range of zero to 50% of the F3 patients
may progress to cirrhosis. I think this really just illustrates that we have not studied this well yet, and there's a lot of uncertainty of who is and is not going to progress. But we think that a significant
proportion of patients with cirrhosis will actually
need liver transplant or die from liver related causes. And a smaller proportion
may develop liver cancer or who had a cellular cancer. So I've mentioned some
of the liver-related consequences of NAFLD, but it's really important
to know that there are other major causes of death in
patients who have fatty liver. And in fact, liver is not
the primary cause of death in many of these patients. Heart disease is the
leading cause of death in patients with fatty liver. Which I think is not really surprising because we're dealing
with a group of patients who have other risk
factors for heart disease. And it has been demonstrated
in several studies that fatty liver actually adds
to the risk of heart disease in addition to the classic risk
factors that we think about. Cancer is very, very common
in patients with fatty liver, and some of this is liver cancer, but some of this are other types of cancer such as breast cancer,
colon cancer, you name it. And then the number three
leading cause of death is end stage liver disease, so liver failure related to cirrhosis. So going back to why I biopsy patients, it's very important for me to understand how severe their liver
scar is, and that's because the severity of the liver fibrosis is the most important predictor
of how patients will do. Patients who have more
advanced stages of fibrosis, stage three and four, are much more likely to
have liver-related death. We also know that patients with NAFLD are at risk for liver
cancer, as I mentioned, and this risk is seven
to eight fold greater than the general population. The risk in NASH cirrhosis
is not totally clear, but based on the few studies
that have been published, the risk appears to be anywhere from 6.5 to 15% after five
to 10 years of follow up. Unlike other liver
diseases where liver cancer tends to develop only in
the setting of cirrhosis, we're not sure that cirrhosis
may need to be present for patients to develop liver cancer. Though the true risk of liver cancer and non-cirrhotic NASH
is really not clear. There have only been a couple of studies that have actually looked at this, and even though they did a really nice job of trying to account for
misdiagnosis of lack of cirrhosis, they're still concerned
that some of these patients may have actually been cirrhotic. So I would say this risk of liver cancer in the absence of cirrhosis
is not very clear, but much, much lower than
if cirrhosis is present. So, me being a transplant hepatologist and interested in NASH,
it's important that I know that NASH is actually
increasing as a reason why people need liver transplantation. And one of the reasons
why this is happening is that hepatitis C, and
you can barely see it at the end of this graph
here, but just trust me in knowing that hepatitis C
has gone down substantially as a cause of end stage liver disease and need for liver transplant. Which is an amazing thing,
because there are wonderful drugs out there that can
actually cure hepatitis C. We don't have that yet
for fatty liver disease. But thankfully, again, so many fewer patients
will need transplant. But what we are seeing is that NASH is increasing as an indication
for liver transplant, and it really is neck and neck
with alcoholic liver disease. What we see in women is that NASH and this red line here
is the number one reason for people that need liver transplant. So, NASH is the number one indication for transplant in women. Alcohol-related liver disease is the leading indication
for transplant in men. So these are really the
two groups of patients that we are doing transplants for. And a lot of these patients will also have liver cancer at the time
of transplant as well. So I've talked to you
about the complications of fatty liver disease, both
liver and outside of the liver, and I want to talk with
you a little bit about what treatments may be
available that can improve NASH. Now, I don't know if
any of you were hoping for a silver bullet, I am sorry to say I do not have a silver bullet for you. What I'm gonna tell you
may be a little bit boring. I know supplements are very, very popular to treat a variety of conditions, but unfortunately, there
have not been really any supplements, with rare exception, that have been shown to be beneficial to treat fatty liver disease. One of the other issues is
that a lot of supplements that are out there, we
don't know what's in them. And this has really
emerged as a big problem, that what is on the label may not match what is actually in the
pill that you are taking. And what you're taking may end
up being toxic to the liver rather than helpful. These things also tend
to be quite expensive. So for most supplements, I say, really, it's not necessary,
it may be harmful, and it's very likely to be expensive. There are a few that I may be okay with, and I'm sure that will
be some of the questions that I'll address at the end. So what I'm gonna tell you,
again, is very, very boring, and probably things that
you've heard already, that weight loss is extremely important. So weight loss has actually been studied to treat fatty liver disease, and the threshold of weight loss that is necessary to improve
NASH and liver fibrosis is seven to 10% of the baseline weight. Which may be a lot for some people, if you're starting out at 300, 350 pounds, that's a lot of weight. And fewer than 10% of
patients will actually achieve a sustained weight loss of this amount. But if they do, they're likely to have excellent long term benefits
on their liver disease, as well as their overall health. And how are you going to lose the weight? Well, one thing that's extremely important are dietary changes. So I counsel my patients on the importance of portion control and avoidance
of simple carbohydrates, particularly avoiding
fructose-sweetened beverages. And you can see the
alarming amount of sugar that is in each and every
one these drinks down here. And thankfully, UCSF
does not allow the sale of any sugar-sweetened
beverages on campus, and I think that's a great thing. When I'm talking with my patients, I really try to dig into the details of what are you drinking? Because sometimes, it
may not be obvious that patient may be drinking
two cans of soda per day. And when you add that up,
that is 300 calories per day, which then equates to
2100 calories per week. 2100 calories with zero nutritional value and contributing to weight gain, insulin resistance, and fatty liver. So, I think everyone should not drink sugar-sweetened beverages,
but particularly if you have fatty liver, you should
definitely not drink this. I also think you shouldn't
drink fruit juice. Even if it's kind of 100% natural juice, you're still mostly drinking
kind of liquid sugar. And if you tried to eat the
amount of fruit that it takes to make that one glass of juice, you would not be able to do it. And you'll have fewer
of the health benefits that you do from actually
eating the fruit. You'll feel less full if you drink juice rather than eating a piece of fruit, so much better off eating
fruit than drinking it. Another thing that's
extremely important, again, for general health, but also
for fatty liver disease, is exercise. And exercise has been
studied in various forms, and has been shown to reduce liver fat when patients were compared
before and after using MRI. And the specific thresholds for exercise that need to be met to have an impact are at least 150 minutes per
week of aerobic exercise, and that's in the moderate
to vigorous range, and I'll tell you what that really means, or resistance training 45 minutes a day, three days per week. And these really match
the CDC recommendations for physical activity in
the general population. So I will tell you, if I'm
first meeting a patient in my clinic, and if
they've never exercised, I will not mention these amounts of time. Because that's a really
surefire way to scare someone out of my clinic and never come back, because they'll worry, I can't do that, and she's gonna get mad
at me if I come back and I haven't done that. So I really try to
individualize my counseling and try to work with
the particular patient to try to figure out what
exercise is feasible to them. What can they physically do, and what are they actually
going to stick to? Because a lot of times I
hear, oh, I have a treadmill, I have an elliptical or stationary bike, and they've had it for 10
years and they're not using it. So my next question is,
how many pieces of clothing are hanging on that piece
of exercise equipment? And also, what makes you
think you're gonna do it now versus before? So I think it's really
important to have these detailed conversations
and really kind of the back and forth of planning, what are you gonna do for exercise, what is really gonna work for you? And then thinking about,
well, what is categorized as light, moderate, or vigorous exercise? So light exercise is walking slowly, working on the computer,
cooking, washing dishes. Moderate, walking briskly, light biking, vacuuming, mowing the lawn. And then vigorous, jogging,
fast biking, Zumba, which I am a huge proponent of because I'm also a Zumba instructor, and then shoveling or
carrying heavy loads. But really, even though I've categorized these specific activities
as moderate and vigorous, I'm really thinking of this cartoon here. This is a cartoon version of a scale that was developed
for exercise physiologists to look at rate of perceived exertion. And this is supposed to
correlate with the heart rate that patients may be generating. So I really want my patients
to get into this range. And sometimes people are
really down in this range, that I'm strolling for an hour with my dog that stops every two
minutes to sniff the grass or the fire hydrant or whatever. So I really encourage people to kind of increase the
intensity of exercise if they're already doing something. And the nice thing about that is that it might actually decrease
the amount of time that they need to exercise. So maybe that hour of that light stroll may not be achieving
that much metabolically, and if they increase the intensity, maybe it's only 15 or 20 minutes. And they're gonna get
more benefit in that way. So I do know, though, that
there are a lot of barriers to exercise, particularly
in this patient population. And I had mentioned already
obstructive sleep apnea, that can contribute to
fatigue and headache, which is gonna make it
really hard to kind of get that oomph to start exercising. Osteoarthritis can cause
pain, decreased mobility. Depression can lead to decreased activity and decreased motivation. There may be balance problems,
generalized weakness, because we do think
about this thing called sarcopenic obesity, which is basically reduced muscle mass
despite excess body weight. There can also be some fat
deposition in the muscles which can actually decrease
the muscle strength and the muscle functioning. Kind of like thinking about a ribeye steak that has that nice
marbling, the same thing can happen to the muscles. And then finally, potentially
cognitive deficits. So, in thinking about
what is this prescription for exercise, we have to think about using different behavioral strategies. And these are the things
that I kind of have in mind when I'm talking with the
patient and working with them and trying to figure out, how
can I get you to exercise? Thinking about, well,
how can I motivate them? Some people may be motivated by, I don't want my liver to fail,
I don't want to transplant, so I'm gonna do whatever I have
to to keep my liver healthy. Are these goals attainable? Again, sometimes the
first time people meet me, I say, okay, well, what are
you gonna do for exercise, how many days per week? Well, I'm gonna exercise
every day, an hour each day. Well, that's great if you
do that, but you know, it's okay if you don't, and
why don't you set that goal of exercising maybe one or
two days a week just to start and do that for a while, and
then gradually ramp it up? You want their goals to be measurable. Again, number of days, number of minutes. You want them to have a
memory of what their plan is once they leave my office. Having positive thoughts around exercise. I think, again, for people
who may not have exercised before, there's that dread of, oh, I have to exercise,
it's gonna feel bad, I'm gonna feel bad afterwards. And really trying to get into
that positive mindset of, yeah, it might be hard to start, but this is gonna have such a
great impact on your health, and ultimately, you're gonna feel better. You wanna reinforce any behaviors that people are already engaging in. Again, if someone is already
walking for exercise, even if it's at the strolling pace, I give them that positive
reinforcement of, great, you are doing something,
and that is awesome. But I want you to ramp it up a little bit. Environmental support. So a lot of people think
about walking as a great form of exercise, which it is,
again, it's accessible, unless you live in an unsafe neighborhood, then walking may not be
realistic for everyone. Have to think about stress management. Again, I have patients
who have two jobs plus. Maybe they're driving two hours
to and from work every day and they are the breadwinner and the caregiver for their family, and adding on exercise may be
additional stress for them. Social support. Now, if you have kind
of a partner in crime to do your exercise, maybe
they're gonna hold you accountable and you'll
hold them accountable. And it's gonna be more fun
and a more positive social interaction rather than
this task of exercise. And then finally, problem solving. If you see, okay, well, this
person may have the time, how can I figure it out to really put exercise into their schedule and kind of book that appointment for them to do exercise for themselves? So, we do know that despite our counseling with the importance of improved
eating habits and exercise, it's still really hard to lose weight. And particularly if you
have a body mass index of 40 or above and you haven't
successfully lost weight in the past, it's gonna
be really challenging. So I am actually a big
proponent of bariatric surgery. And I think some people think about this, well, it's a failure, no, it's
really hard to lose weight. I told you only 10% of people get the amount of weight
loss that they need. So I look at bariatric surgery
as a really important tool to help manage medical
problems for these patients. And the procedures that we
think about being most helpful are sleeve gastrectomy,
basically cutting out a big chunk of the stomach and leaving the patient with a tiny remnant stomach. Roux-en-Y gastric bypass, I think this is the one that
people know the most about, it's been around for a long time. Lap band I don't love because
there are a lot of long term complications related to the foreign body. We do see that with bariatric surgery, there can be improvement in NAFL and NASH, as well as improvement in liver fibrosis. Though if a patient has
progressed to cirrhosis, it may be challenging to
actually do bariatric surgery. But if the patient is at a center that has expertise with
this patient population, and the surgeon has experience
operating on patients with cirrhosis, then it can
be successfully carried out, but the operation of choice is a laparoscopic sleeve gastrectomy. We're lucky to have one of
our transplant surgeons, Dr. Andy Posselt, also
be a bariatric surgeon, so he does our sleeve gastrectomies
in our liver patients. Now, I mentioned that the
leading cause of death in fatty liver disease is cardiac disease. So it's really important
that the metabolic syndrome problems are well treated in
patients with fatty liver. Because this is a common
question that I get from patients and physicians alike. Well, can I use a statin,
is that gonna hurt my liver? And a lot of patients might
have stopped the statin before they saw me because the
liver enzymes were elevated. And what I will tell you is that statins are absolutely safe for use in NAFLD. And we used to think that
they might actually help fatty liver, because some patients may have some improvement
in their liver enzymes, there may be reduced risk
of liver-related death or hepatocellular cancer. But when statins were studied
in a well controlled manner, it did not look like they
had an independent impact on improvement in fatty liver. So statins are recommended for treatment of elevated cholesterol or heart disease, but not recommended
specifically for fatty liver. Metformin, the way that it works, for all intents and purposes,
it should help fatty liver. And some studies have shown improvement in liver biopsy and
liver enzymes, but again, when this drug was studied
in a well controlled manner, it did not appear to have
an independent impact on fatty liver disease. But it is safe for use in fatty liver, and it's a really good drug, and it may have some
important anti-cancer effects. So these are two drugs,
which are, I think, really important tools in the treatment of diabetes and hyperlipidemia,
but they shouldn't be used just for treatment of fatty liver. So what do we have to treat fatty liver? Well, it's not much. So, one important point is that only patients who have biopsy-proven NASH actually need liver-specific treatment. And what we have available
to us now is vitamin E and pioglitazone. So pioglitazone, Actos
is an older medication that is used to treat diabetes. So these two medications,
pioglitazone and vitamin E, were compared with placebo
for treating patients who had biopsy-proven NASH. It's important to note that in this study, patients were only non-diabetics. And what was seen was that the patients who were treated with vitamin E had much more improvement
than the patients who were treated with
placebo or sugar pill. They also had more of a response than patients treated with pioglitazone. It looks like the
pioglitazone-treated patients did have a substantial response, but because of the way the
statistical analysis was done, we can't definitively
say that pioglitazone was effective in this study. Another thing that I
think is important to note is that there's about a 20% response rate of placebo or sugar pill, probably because people
changed their behavior when they were in the study. So in practice, what I do is when patients have biopsy-proven NASH, I use vitamin E regardless
of whether they are or not diabetic. That is against the official guidelines, but we don't have any data
to suggest that vitamin E is dangerous in patients with diabetes, and I don't really have anything
else to give them just yet. You can potentially use pioglitazone. I don't like that drug
because it causes weight gain. And if we're telling
patients to lose weight and we give them a drug that
causes them to gain weight, I think that's pretty awful. And also there are much, much better drugs to treat diabetes these
days than pioglitazone. So there's a lot of work being done for treatment of fatty
liver, and some of the drugs that are actually on this slide have since been shown to not be effective. But what I will show you is that there are a lot of different targets that are being looked at for
treatment of fatty liver. So some of this is the formation or deposition of fat within the liver, as well as inflammation
and liver cell death. Liver scar is being targeted as well. And then at the level of the intestine, there are a lot of drugs
that are looking at blocking absorption of fat or changing the bacterial
makeup of the gut, because we think that may play a role in development of fatty liver disease. But we're still far away
from that silver bullet that I'm hoping for. There are three drugs
that are in phase three clinical trials right now,
and I think these are probably the drugs that are
closest to being approved. Obeticholic acid may be
approved in the spring, I'll actually hopefully hear
more about that this week, actually, at our National
Liver Conference. This drug is currently approved for treatment of another liver disease, but not approved for
treatment of fatty liver. And we think that there are
at least 40 other medications that are currently in phase
one and phase two trials. There are others in phase three as well. But phase three is kind of the large scale clinical trials where we're trying to figure
out, is the drug effective and what dose is the most effective and safe for the particular condition? So there will be a lot coming
out in the coming years. So just to talk a little
bit about who should be managing these patients. So, I've mentioned a
lot that these patients are typically referred by primary care, and they have a lot of conditions that the primary care doctor treats. So I developed this flow
diagram to think about, well, how should we decide
who comes to hepatology and who really owns the patient? So, the squares in blue are primary care, and green, hepatology. So it's usually the
primary care provider that suspects fatty liver, and
then they refer to hepatology where we do our diagnostic evaluation and think about fibrosis and staging, and we further determine,
do they have NASH or do they have NAFL? And if they have NASH, particularly if they have
fibrosis of at least stage two, then we can think about treating them. Vitamin E, pioglitazone, or
referring for a clinical trial. And then we do want to
follow their fibrosis stage over time either with Fibroscan or biopsy. If the patients are in their
earlier stages of disease, then they can probably
live in primary care with close monitoring and thinking about doing serial Fibroscan. And if there are signs of worsening, then the patient can
come back to hepatology. If they have cirrhosis,
these patients absolutely should be followed by a hepatologist. And we're looking for
signs of decompensation or liver failure, liver cancer, and we're looking for another
complication called varices. And again, thinking about clinical trial. And then really, all NAFLD patients should be counseled on weight loss by both primary care and hepatology. And the primary care
provider should be diagnosing and managing the metabolic
syndrome comorbidities. And they should be
monitoring kidney function, as that is also another
complication of fatty liver in the metabolic syndrome. So before I conclude, I do wanna talk a little
bit about alcohol. I just have a couple of slides, because this is a common question I get. So is it safe to drink
alcohol if I have NAFLD? If so, how much? We don't really know, we're
still trying to figure this out, though there have been more and more data that have come out over time. So, it may be not best
to pair your McDonald's with a lot of pinot noir. But just to tell you what we do know. There was a thought initially that a little bit of alcohol, modest drinking, may actually prevent NASH. And this was based on a snapshot in time looking at a group of patients, and those who drank a little bit tended to have a lower risk of NASH than those who didn't drink at all. However, when these patients were followed over a longer period of time, it was found that any alcohol use may actually prevent improvement in NAFLD, and may increase the fibrosis progression. Once NASH or NAFL is diagnosed, modest or moderate alcohol intake may prevent improvement in NAFL
or NASH, as I've mentioned, and binge drinking, that we know is bad. That's bad for everybody. But it can be associated
with fibrosis progression in patients who do have
pre-existing NAFLD. So, really what we have from
our guidelines are not much, no specific recommendations
regarding safe alcohol intake in patients who have established NASH. Now, what do I actually tell patients? So if you have cirrhosis, if
you have advanced fibrosis, you shouldn't drink at all. It can increase your risk of liver cancer, it can increase your
risk of liver failure. And if you have cirrhosis, you may need a transplant someday. And I don't want a little bit
of alcohol to get in the way of you getting on a transplant
list if you need one. Now at the other end of the spectrum, if you have NAFL, no fibrosis,
normal liver enzymes, can you drink a little bit? Maybe, we don't really, really know. I'd say if a patient has
reached the age of 70 or above, if they have NAFL, if
they have no fibrosis, and they're a light drinker and they haven't had fibrosis progression, they can probably continue
doing what they've been doing. But it's really that
middle group of patients, NASH, NASH with no fibrosis, NASH with a little bit of fibrosis. I don't know exactly what to
tell my patients to be honest, and I'm frank with them in saying that. I don't have great data to
say, this is okay, this is not. So I do err on the side
of being a little bit more conservative, and advising the patients who definitely have liver scar and NASH to really avoid alcohol completely. So, to summarize everything. I hope I've shown you
that NAFLD is common, and most patients with metabolic
syndrome will have NAFLD, with at least 16 million
in the US having NASH. NAFLD is the umbrella term
that includes NAFL and NASH, with NASH having a much
greater risk than NAFL of progressing on to cirrhosis. We do need biopsy to
accurately characterize and stage NAFLD. The leading cause of death in
fatty liver is heart disease. NAFLD is an important
contributor to liver cancer, as well as need for liver transplant. And its management hinges
on weight loss, exercise, avoidance of simple carbohydrates, and metabolic syndrome control. With vitamin E and
potentially pioglitazone being used only for biopsy-proven NASH, but there are many, many
drugs in the pipeline for NASH and fibrosis. We still have a lot of
work to do for fatty liver, not just the treatments. We need to figure out the
best method for screening and diagnosis which patients
are at greatest risk for disease progression,
who goes from NAFL to NASH? Who has NASH or NAFL
progresses to cirrhosis? And then what are the impacts of future treatments on outcomes? Will they reduce the need
for liver transplant? Will they reduce the risk of liver cancer and liver-related death? And what impact will these treatments have on cardiovascular disease? And I am excited about the
drugs that are coming out, but one of the other
lingering questions is, who gets treated and for how long? So I think fortunately or unfortunately, I think I do have job security. Because again, there's
still a lot of work to do both in clinical care
as well as in research. So with that, I thank you. (audience applauding) All right, first question. - [Audience Member] So when
you talked to the slide bout what patients can do
to improve the condition, the headline said NASH, it all seemed focused on NASH, but are you saying that
those things to do, the patient should do, are not appropriate or they'll work for people
with fatty liver disease? - Right, so the question was when talking about all of
these treatments, I said NASH. Does it mean that the other
treatments are not effective or not needed for NAFL? So with medication therapy, we think that only people who have NASH and or liver fibrosis
actually need medications. But if you have just fat in the liver, the counseling is really just
the lifestyle modification. Improvement in eating habits,
reduction in calories, sugar, increased exercise, and weight loss. But the point is, people who have NASH are more likely to
actually develop cirrhosis, liver failure, liver cancer, so they definitely need
liver-directed therapy. For people who just have fat, they're at much lower risk for
cirrhosis and liver cancer, so we should really just focus on kind of the lifestyle changes and maybe not a liver specific medication, though weight loss, 5% body weight loss can actually reduce liver fat. Yes. - [Audience Member] Resveratrol, what role does that play in this scenario? - Can you repeat that, I'm sorry. - Resveratrol.
- Oh, resveratrol, got it. Yeah, so what role does
resveratrol play in fatty liver? It's not clear that it's
necessarily beneficial. It does seem to be an antioxidant, but it has not been well studied for treatment of fatty liver. Think you were next, yeah. - [Audience Member] So, two questions. It sounds like everybody
with any of these conditions, there is no person who is fit and slim. And second question is at
what point would you say that continuum are things
absolutely irreversible? Can you reverse any part of the scarring? - So the first question was, I'm gonna kind of reword it, is every patient who has fatty liver, are they overweight or obese? No, but most are. About 90 to 95% of patients
with fatty liver disease are going to be overweight or obese. There is kind of a subgroup
of so-called lean NAFLD, normal weight, that we're
learning a little bit more about. But the other thing
that's really important is that absolute weight and
BMI are not the most important things, body composition
is really important. And also thinking about different
BMI thresholds for disease that may differ according
to ethnic background. Because we see in particular,
in Asian patients, there are lower body mass index thresholds at which those patients are at risk for things like diabetes
and fatty liver disease. So, again, I do have patients Asian and non-Asian who have a BMI of 22. But they've got skinny little legs, and every bit of their
weight is in the belly. So, I do look at the BMI, but I also look at the patient and what
does the belly look like? And then the other question was, well, how much of this is reversible, and when do we get to
the point of no return? So, definitely at the early stages. NASH, early stage fibrosis,
definitely up to stage two, we really think that the disease can be completely reversible. At the point of cirrhosis, I
think it's much less likely that you're going to go from
cirrhosis to no fibrosis. But we think that the
impact of the weight loss, improved diet, exercise, may at least help to stabilize the liver disease where it is and prevent it from
getting worse over time. With these newer drugs
that may be coming out, they may actually be able
to reverse liver fibrosis. So the real holy grail with
treatment of fatty liver is resolution of NASH. Getting rid of fat, getting
rid of inflammation, and reversing fibrosis. Though if you look at the outcomes for some of the clinical
trials, they will look at resolution of NASH with
no worsening of fibrosis, or improvement of fibrosis at least. So there are different outcomes
that they're looking at, and some drugs,
interestingly, seem to reverse liver fibrosis but have no impact on NASH. So the treatments kind of
beyond the lifestyle changes with regard to the medications, it's probably going to end up
being multiple medications, because that picture, that
cartoon that I showed you of the different potential targets, that is a super, super simplified version of all of the stuff that we already know. And everything that we know, there's probably just as
much that we don't know. So it's a very, very complex disease, and when you perturb one pathway, what do you do to something else? That's something we're
still learning about. Question in the back. - [Audience Member] So I'm
curious as to what is the dosage of the vitamin E that you
recommend to your clients? - So, the dose of vitamin E for treatment of biopsy-proven NASH is 800
international units daily. The brand I recommend is Nature Made. In part because it's a reputable brand. We feel good about the
quality of their products, but also that was the brand
that was actually used in that research study. But I don't recommend vitamin
E if you haven't had a biopsy and you don't have NASH, 'cause
you don't really need it. The harm is probably minimal, but there have been some
studies demonstrating potential increased
risk of prostate cancer, particularly at higher doses of vitamin E, and the potential for
increased risk of bleeding. Okay, and behind you,
there's another question - [Audience Member] Have you noticed that severe carb restriction,
or even a ketogenic diet, can help fatty liver? - Right, great question. So, what about severe carb restriction, or even the ketogenic or keto diet, which I know is very popular these days. So that's also not very well studied, at least in the long term. I know the keto diet is
definitely associated with weight loss in the short term, and may help with fatty liver, but that has not been very well studied. The other problem I
have with the keto diet is that it can be really,
really tough to sustain. Some people can be on it
for a long period of time, but most people, they're just
like, oh, this is just gross, I can't eat this much
fat day in and day out. Yes. - Could you elaborate
on why it's been so hard to develop a drug for NASH? Because it seems like the pathways are pretty well described,
so what has been the nature of the challenges? - Yeah, so why is it so darn hard to actually find a drug
that works for this disease where we already know so
much about the pathway? So, there are so many different pathways. So there's insulin resistance,
which is part of diabetes. There is inflammation and a lot of kind of different inflammatory
pathways, and there is fibrosis. So, a lot of really smart
people at some really top notch pharmaceutical companies have been working on
this, and I think because the disease is so complex and
it's not just one pathway, I think that's why a lot of
the drugs have failed thus far. Because a lot of the drugs
really are kind of targeting one particular pathway, and they're not hitting all
of the different components. Combination therapy really
is starting to be looked at. And I think ultimately,
that is where we're headed. Yes, I think you raised your hand first. - [Audience Member] So I'm
curious as to how safe it is to do the biopsy, because
my concern would be how to stop bleeding. - So, the question was
safety of liver biopsy. It's actually a very safe procedure. The issues that we would run
into with serious bleeding is if you hit one of the blood
vessels that runs in the rib, and it's extremely rare to have really serious life threatening
bleeding or bleeding that requires a blood transfusion. - [Audience Member] So,
besides taking drugs that aren't available yet, you have significant factors,
let's say, in the three range. By living the life of the
saint that you described, is it possible to reverse
the fibrotic scar? - Yeah, so the question was, if you have, say, stage three fibrosis, if you do all of the things that I say, will that reverse fibrosis? Maybe. One of the problems is
that very few people can actually have these sustained changes and have that sustained weight loss. I'm thinking about probably
about two of my patients who have had some substantial
behavioral change. And they had, I think one had stage two, the other had stage three, and at least by Fibroscan,
one of them was re-biopsied, they actually have had
reversal of fibrosis. So it can happen. Will it happen for everybody? Not necessarily. But if you don't make the
changes, then the concern is, that disease processes is still ongoing. Back there. (audience member speaking faintly) So the question was talking about increased
risk of different cancers. So, we know that patients
who have diabetes and obesity are actually at increased risk of a variety of different
malignancies, different cancers, and some of this may be
related to insulin resistance, and that can have an
impact on some of the genes that actually kind of
modify the immune system or the immune surveillance for cancer. So that's really kind
of the thought about why there may be more cancer
in this patient population. Yes. - [Audience Member] Do you
have any special advice for people who have an
immediate family member who does have advanced
cirrhosis due to NASH? - So, what's the advice
for a family member, anyone who has advanced liver disease or advanced fibrosis related to NASH? I would say refer them
to a hepatologist for-- - [Audience Member] The person
who doesn't have it yet. - Oh, who doesn't have
it yet, sorry, I missed. Okay, so a strong family
history of fatty liver disease. What should they do? So, the guidelines do not yet recommend surveillance or screening
of family members who are related to someone
who has had cirrhosis. Though again, I think you have to look at the individual person,
and if you happen to get liver enzymes and they're
elevated or if you happen to have an ultrasound or MRI and
they saw fat in the liver, I think that really does
warrant referral to hepatology. Just because of the genetic link of fatty liver disease, and
some genes have been identified that are associated with a more aggressive disease, phenotype or disease progression. So while we don't necessarily
recommend it widely, if I hear, oh, my mother or my father had cirrhosis and they never
touched alcohol in their life, and you have fatty liver, I'm gonna be more likely to
kind of keep following you in my clinic rather than
kind of dismissing you back to primary care. Yes. - [Audience Member] Let's say that I'm at reduced risk for cancer, let's say I'm confident in that. And I'm feeling fine. And I've got a roaring case
of fatty liver disease, but I'm asymptomatic,
and I may not even know. And I don't really care
because I can drink all I want knowing that any cirrhosis
I'm gonna get is so, any consequences is way in the future. Why should I care? - So, why should you
care about fatty liver? And just kind of do whatever and something's gonna
happen in the future. So, we do diagnose a lot
of people with cirrhosis who have had no symptoms at all. And we find out because they went in for a gallbladder surgery
or a hernia surgery, and then afterwards they
show up to us bright yellow, or they've got a lot
of fluid in their belly because their liver is now failing because they had that stressor of surgery. So if you have cirrhosis, even
if you have zero symptoms, I hope that that will
continue to be the case. But if you have cirrhosis, you are at risk for liver cancer. Again, 6.5 to 15% risk
over five to 10 years, you are at greater risk of
developing liver failure. Are we good enough to figure out, well, this is your
specific individual risk? No, but you definitely shouldn't drink, because that is going to
contribute to ongoing liver damage and increase your risk of liver cancer. You had a question over here. - [Audience Member] Okay, is
non-impact exercise equal to weight bearing exercise,
like a dog in a pool, so is that equal to
weight bearing exercises? - Yeah, so the question was
kind of type of exercise, is the high impact or
weight bearing exercise, is that necessary, or
can it be non-impact? So, resistance training, not exactly what you were talking about, kind of like a water aerobics or swimming. As long as it is
increasing your heart rate or you're doing some sort
of resistance with the water kind of being like your
point of resistance, it should be beneficial. The water aerobics hasn't been
well studied for fatty liver, though, again, any exercise is good. Whether it kind of really reaches that threshold of moderate or vigorous, I think it really depends
on exactly what you're doing and how much you feel like
you're exerting yourself. If you're getting into kind of
like that yellow orange range of that cartoon, then yes,
it probably is good enough. Yes. - [Audience Member] When I was a teenager, we used to have diet pills. And I was just thinking, you
would think that that would be such a mundane pharmaceutical to have appetite suppressants. So what, are there no diet pills? - So, what about diet pills? So a lot of appetite suppressants, particularly kind of the older ones, have actually been shown
to have some problems. Like Fen-Phen has been
associated with cardiac, heart problems. There are drugs that are
being used for weight loss. And again, some of them do
carry certain side effects. There is one drug that's
actually used to treat diabetes that also is approved for management of weight loss, and also may have an
impact on fatty liver, though that's based on a
very, very small trial. Medicine called, brand name is Victoza or generic, liraglutide. So that may be beneficial,
but there are other weight loss drugs that
may actually work on kind of behavior. There's a combination drug,
bupropion or Wellbutrin and Naloxone, it's called Contrave. I think one of the barriers
is that insurance companies don't always cover these drugs. I think you also have to
be connected to someone who has expertise in weight management. So I think there certainly
is a role for drug therapy, but I think you kind of have to find the right drug for a particular person and then get it covered by insurance. Yes. - [Audience Member] Does
not having a gallbladder, does that make any difference
in the risk for progression? - So, what if you don't
have your gallbladder? Is that going to affect your fatty liver or progression of liver disease? Absolutely not. Gallbladder is an extra
organ, it just stores bile. When you get rid of it, it doesn't have any impact
on liver function at all. Yes. - [Audience Member] The
incidence in children that have risk factors, is that studied? - Yeah. So, fatty liver, unfortunately, is being seen in a lot of kids. Not quite at the same
prevalence as in adults, but it's getting there. So it's a huge problem,
because then ultimately, these kids are going to become
adults with fatty liver. And they will become
adults with cirrhosis. And we have patients in our
practice who are in their 20s and they have cirrhosis from fatty liver. So this problem is going to get
worse before it gets better. Yes. (audience member speaking faintly) Good question. So, ethnic-specific
resources for fatty liver. I am not aware of any
off the top of my head, but I think it's really needed, and one thing I always think
about with dietary counseling is when I'm counseling a patient where culturally, rice
is a staple of the diet, and I'm talking about, well,
decrease the amount of rice, eat fewer carbohydrates, that may not be culturally appropriate. So I think that's something
that really warrants additional work for sure, but I can't think of anything
off the top of my head, sorry. You had a question. (audience member speaking faintly) So the question was about, is there an association between
congestive heart failure and fatty liver disease? Not directly. Congestive heart failure
does not cause fatty liver. But if the heart failure was caused by coronary artery disease that was worsened because of diabetes, high blood
pressure, high cholesterol, then fatty liver may also be present, but the two do not directly
link to each other. One more, yeah. - Does fatty liver
involve type two diabetes? That your cells becomes resistant to the. - So, what is the link between fatty liver and type two diabetes? So there's this
bi-directional relationship. People who have diabetes, they're at increased risk for fatty liver. But if you have fatty liver,
that can also increase your later risk of
development of diabetes. And some of it is related to tissue and liver sensitivity to insulin. So, yes, they're linked. All right, I think
we're about out of time. So I wanna thank all of
you for coming out today. You've asked some really great questions, and I'm really happy to be
talking with you guys today. Thank you. (audience applauding) (gentle music)
https://twitter.com/DBrandmanMD/ - she doesn't seem to be directly recommending keto - just low sugar/fruit juice, and exercise.
She essentially just says lose weight, exercise, and donโt drink soda and other high sugar content drink. She also mentions that most liver supplements are garbage and doesnโt recommend any to the already healthy person. Nothing really groundbreaking here, but still a good review