Liver Diseases (Hepatology)

Alcoholic hepatitis, or alcoholic liver disease, is inflammation of the liver caused by drinking alcohol. According to UChicago Medicine experts, liver transplants for patients with alcoholic hepatitis have increased almost 500% from 2014 to 2019. And many believe the COVID-19 pandemic has only fueled this trend. Our experts will discuss this situation, to take your questions live. That's coming up, right now, on At the Forefront Live.

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And we want to remind our viewers that today's program is not designed to take the place of a visit with your physician. Let's have each of you introduce yourselves. And tell us a little bit about what you do here at UChicago Medicine. Dr. Charlton, you're on set with me, so we'll start with you.

Thank you. I'm Dr. Michael Charlton. I'm a Professor of Medicine here, at the University of Chicago, and co-director of the Transplant Institute, together with Dr. John Fung.

And let's go to Dr. Fung next. He joins us from Studio B.

Hi, my name is John Fung. And I'm the co-director, with Dr. Charlton, of the Transplant Institute at the University of Chicago. I'm a Professor of Surgery and the chief of the section of Transplant Surgery.

And our next expert to join us is Dr. LaMattina, who is also back in Studio B. And Dr. LaMattina, you're up.

Hi, I'm John LaMattina. I'm an Associate Professor of Surgery here. And I have a particular interest in liver transplantation and living donor liver transplantation.

And I want to welcome you to the Chicago area. You're relatively new here, so we're excited to have you here.

Good to be here, thank you.

All right, Dr. Charlton. And we're going to start with you on this one. And we'll just go with some basics. First of all, that statistic that we heard in the open was a little startling, 500%.

It is, yeah.

Talk to us just about liver damage. And what are some of the signs that a person might have liver damage from alcohol?

This is an important question. For most people with chronic liver disease, or the disease is going on for some period of time, there's usually no symptoms. Most people are unaware of their liver disease. It's often found serendipitously, or by chance.

When liver disease has progressed to some degree, what we call end-stage liver disease, often in association with a lot of scar tissue or cirrhosis, you can get a number of things. You can become jaundiced, or yellowness of the eyes or the skin. You can have an accumulation or collection of fluid in the belly. So you get what we call ascites, and the belly may become distended.

And then, there are other, obviously alarming symptoms, like the vomiting of blood, blood in the stool, or some change in stool color that would be concerning for bleeding. Then, other things-- like general weakness is a common symptom as well. Those are the things that people may get. But mostly, people have no symptoms, other than perhaps tiredness.

So that's part of the challenge with it, it sounds like. If you don't have symptoms, I would imagine, sometimes, you don't know until it's maybe a little late.

That's a perfect way to say it. I would agree, yes.

Oh, that's frightening. So we've heard a lot about alcohol abuse, during COVID-19 in particular, various factors for that. What is considered to be alcohol abuse? Is that a drink a day? Is that five drinks a day? How do you measure that?

So there's a number of ways to measure. The World Health Organization considers-- if you have more than an average of two standard drinks per day, if you're a woman-- it's the equivalent of, say, two glasses of modest poured wine or regular beer-- or three a day, if you're a man, anything above that is excessive. That's a pretty substantial intake before it's considered to be excessive. But those are reasonably well-accepted criteria or guidelines for what's safe drinking worldwide.

Having said that, the pandemic really has been good for very few people, outside of a few tech companies. But there were recent data, in the Journal of the American Medical Association, showing that alcohol sales in the United States, year-on-year, increased during the pandemic by over 30%, nearly a third, and at least 12% of increase in consumption. So it's really been a dramatic increase in alcohol intake. So the data that you were talking about, this 500% increase? That predated the pandemic. So we're expecting to see a super spike in months and years ahead.

And I know this is anecdotal at this point, but you and I were speaking before the show, and you were saying how busy your team has been throughout the pandemic. It hasn't let up, obviously.

No. Here, at the University of Chicago, we did more liver transplants than we've done for, probably, two decades and, without doubt, the largest increase in liver transplantation for alcoholic liver disease that we've seen as well here, at the University of Chicago. So we're seeing it firsthand, this spike in alcohol-related liver disease, which is longstanding and also, most notably, this very acute, sudden, catastrophic liver failure related to excessive alcohol consumption.

So now that we have everybody at home worried, Dr. Fung, I want you to join us if you can, and talk a little bit about alcoholic liver disease. Can that be reversed? I mean, we're going to talk about transplants, obviously, in the program. But can that be reversed, and does a liver ever heal itself?

So early on-- alcohol is a toxin, a hepatotoxin, as we say. And taken in modest amounts, it doesn't damage the liver, under the threshold that Dr. Charlton was talking about. Excess of that, though, will start to cause liver inflammation and then subsequent scarring.

Early scarring is, at least, reversible to some degree, if you stop drinking. As it progresses, though, the scar tissue becomes firmer and firmer. When you get well-established cirrhosis, it generally doesn't reverse to the extent that you go back to normal liver. You may mitigate some of the complications of alcoholic liver disease. But well-established cirrhosis tends to continue to be progressive.

And when we are talking about cirrhosis of the liver, that's scarring of liver. That can be caused by a lot of different things. I mean, obviously, we're talking about alcohol today. But scarring of liver can happen other ways as well. Is that correct?

Yes. And what Dr. Charlton is referring to is, really, liver disease associated with alcohol abuse, alcohol overindulgence. We do know that there are diseases that people have that make you more prone to the effects of alcohol as a toxin. Some of the enzymes, like alpha-1 antitrypsin deficiency, which is a protective enzyme in inflammation-- when you have a deficiency of that, it exacerbates the toxic effect of alcohol. So they can be additive or even synergistically damaging to the liver, two different processes actually leading to more damage than either one alone.

Oh, that's interesting. And I would imagine a lot of folks, probably, aren't aware of that. Dr. LaMattina--

That's true.

Oh, go ahead, I'm sorry.

[? Though ?]

that's true, as Dr. Charlton said, it's a quiet disease, liver disease. And so people may have something, a genetic disease or have acquired something like hepatitis C or hepatitis B. And they're, then, secondarily exacerbating the effects of that disease by consuming alcohol.

So Dr. LaMattina, let's bring you into the equation now. Is there a population that's affected by alcoholic liver disease more than others?

I think there's a population that I'd specifically like to talk about. And this is something that I've been interested in, really, for about the last 10 years. And that is patients that come in with some degree of acute on chronic alcoholic hepatitis. Historically, based on studies in the 80s with very little numbers of patients honestly, people would say, if you have alcohol in any way really, contributing to your liver disease, we're not going to move forward with transplant. We're not going to consider you for transplant, really, until you've had six months of sobriety. And that was really standard of care, even six years ago.

But about 10 years ago, we had a patient of ours that we had turned down for transplant, because they didn't meet these very strict inclusion criteria. And this was a young person that had children of their own, that had a very supportive family, but really had not had the chance to prove that they could go the whole six-month period. And we were actually reapproached by our ethics department in the hospital and said, do you really think this is the right thing to do for organ management, for the US health care system, for this patient in particular?

And that really started us thinking about, how do you adapt a very rigid and strict protocol, in particular with alcoholic liver disease? So we ended up moving forward and transplanting that patient. And that sort of changed how I approach things, how I thought about things. So it really, at least for my practice over the last decade, this has evolved. And that really has almost become the standard of care now.

So if we have someone that comes in with alcohol contributing to their liver disease, whether it's the sole contributor, as Dr. Fung said, it's one of a number of things contributing to the liver disease, we really take a very multidisciplinary approach here and, very early on, the hepatologists are typically the first line in. And then, we very quickly involve the surgeons, our case managers, our social workers, and our psychiatrists to say, can we come up with a plan that will enable this person to get better? And if they can get better without transplant, great. But if they can't get better with transplant, how can we get them into a position that they will be an appropriate candidate for a transplant and then do well after a transplant?

And there are certain groups that we look at that, in our experience, have really shown that it doesn't look like they're going to get better. And they're not going to have that period to show that they can break their relationship with alcohol. And these are a challenging patient population. They're typically in the ICU, on dialysis, on medications to keep their blood pressure up.

And for those patients, such a high percentage of them are simply not going to get better without transplant. We want to give them that benefit, which is typically a lot of work with them, a lot of work with their family, a lot of work with our entire team to get them to a position that not only can they get medically stabilized to get through a transplant, but then, can they take care of the organ afterwards? And it's a huge investment for a given patient and their family and their support structure, as well as our team.

But we really do feel like we've come up with a model that we can get patients to where they're not just going to do well this week, next week. But they're going to well one year from now, three years from now, 15 years from now after a transplant. And that can be a very rewarding aspect of the job that we all do together.

I'm glad you brought that up, because that is a question or a thought that we hear all the time when we're doing programs like this. You read about it. There will be a lot of folks in the public that will question the viability of giving someone who has abused alcohol a new liver. But ultimately, I think what we're here for-- or, you're here for, is to save people and help people. And that's what you do. And it's this big team approach that Dr. LaMattina talked about.

This is an absolutely critical point. So making sure that we're using these precious donor organs in a responsible way is paramount. And one of the things that came out of this national analysis was the outcomes. So the Centers for Disease Control projects that there are about 22,000 deaths related to alcoholic liver disease in the United States, per year. 22,000. The number of people who undergo liver transplantation for alcoholic liver disease in the United States, we now know is 3,100 and a bit.

So it's a tiny fraction of patients, who are dying from alcoholic liver disease, are candidates for and get liver transplantation. So this is a very selective group of patients. The great majority, for one reason or another, whether it's health instability, they're just too sick for a transplant, or multiple chemical dependencies, other issues that make candidacy too precarious-- right now, I think we're super selective, as a country, and probably too selective.

The number of patients who have acute alcoholic hepatitis-- so this isn't someone who was drinking for decades. This is somebody who has sudden, catastrophic liver failure related to alcohol. The total number of transplants for that in a year is about 150. And bear in mind that 22,000 number of deaths. So it's this tiny fraction.

And the last point I would make on that is we looked at outcomes. So how do patients, who were transplanted for alcoholic liver disease-- how do they do, in terms of how does that graft survive? How many of those are surviving at one year, two years, et cetera? And we found that outcomes in people transplanted for alcoholic liver disease aren't just as good as others, they're the best of any group that we considered.

Really?

So I think that highlights the very strong consideration that transplant centers are giving to making sure that patients who were transplanted for alcoholic liver disease are able to take care of the grafts, and they seem to. If you measure it by graft survival, it's as good or better than any other group.

So what do you attribute that to? That's an amazing statistic. Is it just because there's so much care that goes into working with those patients and making sure that they're ready?

The first adult to get a liver transplant, in the whole world, was a man with alcoholic liver disease. And so it's something which has been an issue from the very beginnings of liver transplantation, since Professor Thomas Starzl did the first one in 1963-- reported them, in any case-- to today. And I think that the need for it has only increased over time. And our ability to do them successfully has been key.

I think we are very concerned about not wanting to be seen to be using organs in a cavalier way. And based on these data and the outcomes, I think we're being, as I said, super selective and careful in consideration. And I think, probably, too much so. I think only transplanting 150 out of 22,000 people who are dying from it, that's probably not enough.

So we are starting to get questions from our viewers, which we always welcome. And I want to get to as many of those as we can during the program. And we'll start off with Dr. Fung on this one. I'm going to actually combine two questions, Dr. Fung. So the first one is from Carmine. Do ibuprofen or other over-the-counter drugs play a role? And the second one is from Sandra. What role do statin drugs play in the liver?

Well, statin drugs really tend-- that's not really a drug that we are concerned about co-mingling with alcohol. It has its own toxicity profile. But it's uncommonly associated with liver disease, even though we check liver function tests when we prescribe it. I think the first question of the anti-inflammatory analgesics, ibuprofen and particularly Tylenol-- Tylenol is hepatotoxic at higher doses. And we know, from past studies, that alcohol combined with Tylenol lowers the threshold for which alcohol can cause liver damage.

So we don't really recommend trying to take both of them. When you're getting a hangover, to take a lot of Tylenol and then drink to chase it, probably not such a good idea. Ibuprofen does have-- the nonsteroidals do also have a smaller degree of hepatotoxicity. But generally, if you stay within the drug recommended dosing, it's not such a problem.

Interesting. So here's one. I always love to pass these along. This is a compliment from Anna and says, this group gave my father a second chance to live a better life. I can't thank them enough. So that's kind of--

That's good to hear.

--nice to hear. Here's another one. And Dr. Charlton, we answered this one earlier. You answered this one earlier. Dr. Fung did, actually. But this is kind of a twist on it. Can the liver repair itself if you're still drinking? And if you stop drinking, can it then repair itself? I think that's-- we talked about a little bit, but a little bit of a different twist on it.

Yes, this is one of the most vexing and difficult issues in caring for patients with liver disease in that the liver has a tremendous capacity for recovery. Dr. Fung and Dr. LaMattina will remove up to 2/3 of somebody's liver, in living donor liver transplantation, and that remaining third has regrown to almost a full size liver within a month or so. Having said that, an alcoholic liver injury is very unpredictable.

One of the things that we saw in this national study was that patients with alcoholic liver injury, acute alcoholic liver failure, that the decline can be very precipitous. So patients can come in looking like they're probably going to be OK. And then, in a day or two days, all of a sudden, the blood pressure is unstable. Their kidneys are not functioning. There's a type of kidney failure specifically associated with sudden onset of liver failure.

And the sooner that somebody is considered to be in danger of life-threatening liver failure, they should be considering whether liver transplantation is an option. Based on this tiny fraction that we see of people actually undergoing liver transplantation, we think that the referral rate is much too low. It was also apparent, in the study, that the frequency of liver transplantation for alcoholic hepatitis in the United States varies eightfold between geographic regions. Eightfold.

So if you hear a no initially, at a center, be your own advocate or have a family or loved one be an advocate for you. Make some calls and see whether that would be true somewhere else as well, because there are enormous variation between regions and also between centers.

Great. So Dr. LaMattina, this is one we're going to throw at you. This from Karen. And Karen's wondering, why the increase of transplants? And the second part of the question, were you able to use livers from deceased COVID patients? So a bit of a hot button question there, I think.

All right. Thanks for your question. I'll do the second one first. So we have, personally, used donors that have had prior COVID infections. Each time-- although it's becoming a little bit more routine, we do treat it, each time, as we're starting over again, reinvolve our infectious disease colleagues, do a number of blood tests, as well as a number of imaging tests of the body before we would even utilize the donor. But that has been a source of organs that we have used safely and gotten people home to their families using those organs.

And then, if you could say the first part of the question again? I wasn't quite clear on it.

Just wondering, in general, why the increase in transplants?

The increase in transplants for--

Just in general liver transplants.

In general. Well, so in general, I would say, for liver transplants in the United States, we've been relatively static in terms of the number of transplants that we've performed as a country, generally ranging in the sort of 5,000 to 6,000 level over the past decade or so. Within that overall number of transplants that we do, what you will see is a changing reason for transplant. So 20 years ago, very few people got transplanted for fatty liver disease. That's becoming more common now. As we've been able to treat hepatitis C, we anticipate that the number of transplants that we do for that indication will go down.

We have seen an increase in the number of patients that have undergone transplant for liver disease that has some association with alcohol, whether it's the primary or secondary cause. I think a main reason for that is the recognition that with appropriate support, both from the family as well as the entire care team, these patients can do quite well. So we're offering transplant and considering people as candidates that we might not have considered really even five years ago.

And also, we're considering donors that we may not have considered at one point. Would that be accurate?

That's certainly true. I'm just going to go back to a couple of things that Dr. LaMattina said. We transplant around 8,900 livers a year, and it increased, actually fairly substantially, over the last five years, really in concert with opioid deaths. So as everyone who's watching this will know, there's been an epidemic of opioid dependency in the United States. And there's been a tenfold increase in deaths related to opioid use. And many of those patients end up as organ donors. So a lot of the increase in liver transplantation has related to that.

Within donors as a whole, we've started to use organs from patients who have hepatitis C, for example. So organ donors who have active hepatitis C infection, we now know that we can easily treat that following liver transplantation, or any other organ-- heart, liver, kidney, lung-- all of them have used organs from donors who have hepatitis C infection.

And we're starting to push the boundaries. We're learning that you can transplant from donors who are older than we used to think sensible and, also, what we called donation after cardiac death as well. So the pool has expanded in general, but most dramatically in donors who have experienced opioid overdose.

Interesting. So Dr. Fung, how long does it take to get a liver transplant?

Well, the waiting time really depends on geography, where you live in the United States, and also your MELD score. The MELD score stands for Model for End-stage Liver Disease. It is a combination of three factors, blood tests-- bilirubin, your ability to clot, and your kidney function. And that's calculated into a numerical score. And then, you're prioritized based on that.

The geographic differences, I think, will start to change as the distribution of organs has become broader. But we are seeing that the MELD score, now, is driving the priority. So the higher the MELD score, such as patients that we're talking about here-- the acute alcoholic hepatitis patients tend to have very high bilirubins, have bad kidney function, and coagulopathy and they're in the ICU on life support. So they're prioritizing those patients because of their physiologic risk, the status in their risk of dying.

In those patients, the waiting time can be anywhere from days to weeks. But for somebody who's generally at home, has chronic, stable liver disease, depending on the blood type also, it can be months to maybe one or two years.

So you mentioned geography a moment ago. And part of that is due to the fact that you just can't have the organ outside of the body for an extended period of time. Would that be accurate, or am I off on that?

Well, we try to get the organs in as quickly as possible. They tend to do better when they're in the icebox for a shorter period of time. That's called cold ischemia time.

But the geographic distribution, now, is enhanced. In other words, rather than looking at going into the same city, for example, or the same state, we are able to expand, to go outside that by looking at concentric circles, using distances of 200 to 500, 750 miles, and bigger, to try and capture the sickest patients. And we know transplanting the sicker patients will enhance survival more than restricting the travel of organs, because you can go pretty far in 8 to 10 hours, which is usually what we consider to be a pretty safe area, timeframe, for an organ-- in this case, a liver-- to be outside the body before it gets put into the recipient.

Sounds good. And Dr. LaMattina, we're going to go to you with this one, another question from a viewer. Are there any dietary changes, such as increased eating of certain foods or taking of supplements that can help your liver?

And, I'm sorry, this is for posttransplant or pretransplant? Both?

I think pretransplant, for somebody that may not be getting a transplant. Or the things that you can do, just in general, for your health, to keep your liver healthy.

So I think that's a good question. And this is an exceptionally common question that we get from our patients in clinic. And I will tell you, what I generally tell them is, anything that you can do that would kind of be more consistent with a healthy, active lifestyle will help you globally.

Now, to a patient that is really quite ill and is in the ICU in the hospital feeling sick, this cannot help. And this wouldn't help. But for a lot of patients that are stable at home, I give them the same advice I would give my family or myself, in terms of eating healthy and trying to stay active. And anything that they can do, even incrementally, will help us in the OR if it comes to that.

Interesting. So we had that, Did you know, up on the screen. And it references what you were talking about earlier, Dr. Charlton, such a huge increase-- 34% for alcohol, 13% for tobacco, which, obviously, we know is terrible for you. It's really kind of fascinating, to see those numbers, and alarming at the same time.

It is. One of the other interesting pieces of information to emerge recently is firstly, the sales have been across the board. Every demographic has increased consumption on average. The other thing that was interesting though, that there's been a variance in, is the age range. So we've seen the most profound surge in people who were aged 24 to 34. So there's been a particular spike in relatively young people.

And that really reflects what we seem to be seeing in our hospitals and clinics too, which are people presenting at younger ages with sudden-onset liver failure related to alcohol. So young people seem to be particularly struck by this aspect of the pandemic.

That's very sad, particularly at that age. That's tough. Another question from a viewer, Dr. Charlton. Do diabetes drugs affect or potentially increase liver disease, or do they actually help improve liver function, particularly-- it looks like metformin or the GLP-1 class of drugs?

So that's a great question. Overall, diabetes drugs are very liver safe. And I would say, specifically, for the GLP-1 receptor antagonist-- things like liraglutide, semaglutide, which millions of patients take-- we have a lot of knowledge of these. And experience with their interaction with people who have liver disease seems to be not adverse. Metformin, unless you're really unusually sick, it seems to be safe as well. But if you have really advanced liver disease, you should speak to your doctor about whether any drug is safe to take. But generally speaking, diabetes drugs have a good safety profile with liver disease, other than the more advanced or extreme forms of liver disease.

So we've heard a lot about these detoxes, too, that people are trying. Do they help at all?

I haven't found one that does. And there seems to be an infinite number.

There are a lot, yeah.

And I would say most supplements that are billed as liver detoxifying agents are almost certainly not that. And we have a steady-- I'm going to say, trickle. It's not a stream-- a trickle of patients into our hospital who are very sick with sudden liver failure related to agents that were meant to be detoxifying in some way. And they can be things that are very common. Valerian root, which is common in things like teas that help you sleep at night, green tea extract, Jamaican tea, red rice extract-- there are all sorts of things that sound great but are not friendly to the liver.

Interesting. Gentlemen, we're out of time. That was fantastic. You all were great. Appreciate you doing this.

Thank you.

A special thanks to our physicians for being with us today. And a big thank you to those of you who watched and participated in our program today. Please remember to check out our Facebook page for our schedule of programs that are coming up in the future. To make an appointment, go online at uchicagomedicine.org or call 888-824-0200. Thanks again for being with us today, and I hope everyone has a great week.

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