Alcohol-Associated Hepatitis

Podcast Transcript

Dr. Scott Steele: Butts and Guts, A Cleveland Clinic podcast, exploring your digestive and surgical health from end to end.

Dr. Scott Steele: Hi again, everyone, and welcome to another episode of Butts and Guts. I'm your host, Scott Steele, the chair of colorectal surgery here at the Cleveland Clinic in beautiful Cleveland, Ohio. And today I am very pleased to have Dr. Shreya Sengupta here who is a hepatologist and the medical director of the multidisciplinary alcohol program in the Department of Gastroenterology, Hepatology and Nutrition here at the Cleveland Clinic. Shreya, thanks so much for joining us on Butts and Guts.

Dr. Shreya Sengupta: Thanks for having me. I appreciate it.

Dr. Scott Steele: Today we're going to talk a little bit about alcohol-associated hepatitis. Very interesting. I've been waiting to get you on and ask you all sorts of questions. But before we jump into it, can you give us a little bit of background about yourself? Where did you train and how did you come to the point that you're here at the Cleveland Clinic?

Dr. Shreya Sengupta: Sure. I'm a little bit in enemy territory. I'm from Michigan. I did undergrad at the University of Michigan, and then I moved to Chicago for about 10 years where I did med school and residency. So med school at the University of Illinois, residency at the University of Chicago, and went back to University of Michigan for hepatology gastroenterology training. And then Cleveland had the right job when I was interviewing at the end of fellowship, and so that's how we made it here.

Dr. Scott Steele: Well, as a Badger, I can tell you I don't like Illinois or Michigan.

Dr. Shreya Sengupta: There you go.

Dr. Scott Steele: You kind of fail on both remarks. Thanks so much for joining us here. And today we're going to talk a little bit about alcohol-associated hepatitis. So first let's take a step up from alcohol-associated hepatitis and just tell us a little bit about hepatitis? What is it? And give us a little bit more background there.

Dr. Shreya Sengupta: Sure. Hepatitis is just a pretty general term. It just means inflammation of the liver. And I think when people think about hepatitis, they probably think about viral hepatitis, so hepatitis A, hepatitis B, hepatitis C. Anything can really cause liver inflammation. The liver's very happy to get injured. That can be toxins, it can be medications, it can be autoimmune hepatitis, it can be viral infections. And then, of course, alcohol can cause liver inflammation and liver disease. The liver is a pretty vital organ. It processes nutrients, filters the blood, and fights infections. So, it has a lot of roles but has a lot of different ways it can get damaged.

Dr. Scott Steele: So, how does alcohol fit into that? I understand the virus thing, but why alcohol and why liver? Why doesn't it affect other organ systems?

Dr. Shreya Sengupta: The mechanism of alcohol-associated hepatitis and alcohol-related liver disease is pretty complicated. So, it's not just one mechanism, not just one injury. The idea is that alcohol and its metabolic byproducts, particularly acetaldehyde, and then of course the effects of alcohol on cholesterol, such as triglycerides, all contribute to liver injury. And so that injury leads to inflammation. You get gut permeability, you get changes in the microbiome, you get basically increased oxidative damage. So, there's a lot of different mechanisms through which you can damage the liver through alcohol. So, it's not just one, but really multimodal. And, like gut barrier, gut mucosal integrity and the microbiome have a larger role to play, as we're realizing more and more.

Dr. Scott Steele: What are some of the signs and symptoms of alcohol-associated hepatitis?

Dr. Shreya Sengupta: It can be really non-specific, which is sometimes what makes it a little bit difficult to diagnose. Fatigue, abdominal pain, changes in your menstrual cycle, changes in your sex drive. But more specific symptoms really are weight gain, particularly abdominal swelling, abdominal distension because of fluid in the abdomen called ascites, and then, counterintuitively, weight loss. But not fat, just muscle mass loss. Other signs and symptoms can be day and night reversal, so basically going to sleep later and later until you're up all night and sleeping all day; confusion, which can be seen with encephalopathy. Other things are, of course, jaundice or scleral icterus, yellowing of the skin, yellowing of the eyes, and then very particular rashes. You can get little red dots or what are called spider angiomas, so they look like little red capillaries, little spiders all across your chest. You can get a really specific type of redness of your palms called palmer erythema, bruising. And then, obviously, we talked about jaundice and things like that.

Dr. Scott Steele: Great. So how is this diagnosed, this alcohol-associated hepatitis? Is it something that is a clinical diagnosis, or do you have to get a scan or a biopsy? How does this all work?

Dr. Shreya Sengupta: Yeah. Alcohol-associated hepatitis, per se, is a clinical syndrome, and it has a distinct histopathological or a distinct liver biopsy correlate that's called alcohol- associated steatohepatitis. So, if you were to just get a biopsy in the absence of any information or any sort of context, you really can't distinguish between alcohol-associated steatohepatitis, non-alcohol-associated steatohepatitis, and medication effect. It's really a clinical syndrome, and then you can get a biopsy to clarify any diagnostic dilemmas.

And, so clinically, how do you diagnose it? Basically, onset of jaundice within the last eight weeks, ongoing consumption of alcohol; and I'll talk a little bit more about the amounts because it's a lot less than I think people realize; for as little as six months and no more than 60 days of abstinence before the jaundice starts. When you get liver labs, look for a particular pattern. The AST is elevated more than the ALT and then a bilirubin that's greater than three. There's lots of confounding factors. And so, you can get drug-induced liver injury, you can have other types of liver diseases like autoimmune hepatitis or when people are really sick in the setting of a large GI bleed, or their blood pressure's really low, you can get ischemic hepatitis. So, you really need to make sure you rule out all the other causes but have a high index of suspicion as you're going to diagnose this.

Dr. Scott Steele: Truth or myth: only heavy drinkers can get alcohol-associated hepatitis.

Dr. Shreya Sengupta: I think that is the question of the day, year, month, however you want to say it. That's the question right now. I think a lot of that comes down to what is your definition of heavy drinking? And I think that's where people get a little bit surprised. And so, if you look at the definitions of how much alcohol is enough to cause injury, the guidelines will say it's 40 grams of alcohol for women and 60 grams of alcohol for men.

Now, what the heck does that mean? None of us are looking at grams of alcohol. But if you look at it with the different types of alcohol, a standard drink has 14 grams of alcohol. And then again, once again you get into, well what's a standard drink? And so, people say, oh, maybe I will have a beer or two. Well what kind of beer? What kind of alcohol content? How big is it? Is it one of the craft brews that's seven or eight percent alcohol? Because right there, you're getting 26 grams of alcohol. So maybe one or two of those beers is actually too much for women.

So generally, some sort of rules of thumb really are that a standard drink would be 12 ounces of regular beer, five ounces of wine, or about an ounce and a half of distilled spirits. Each of these contains 14 grams of alcohol. So, if you're a woman, you do the math, you shouldn't have more than a couple. If you're a guy, a little bit more, but still probably not as much as people think. The NIAAA, which is the national institute on alcohol use, has defined binge-drinking as basically four or more drinks in one day for women or five or more drinks in one day for men over the course of a few hours. So, I think those numbers, for lack of a better word, can be a little bit sobering. I think people are probably drinking a little bit more than they realize and need to drink a lot less than they think to actually get damaged.

Dr. Scott Steele: Yeah, I was going to say, why isn't this more common then? Or maybe it is more common, and they just don't know that it's happening. Because it just seems like I went to college, and the reality of the situation is you see a fair amount of this. So, walk me through that.

Dr. Shreya Sengupta: I think it's really shocking for a lot of people. And I have to be honest with you, when I first started learning more about this, it kind of makes you take a step back and look at yourself and where you've been and what you've done. And I think at different points in my life, I shudder to think about whether or not I was coming close to these definitions or not.

I think a lot of it comes from in some ways, I think of where we are now with alcohol is where we were with tobacco in the 1960s. It's widely advertised, it's in grocery stores, it's consumed in movies and shows. It's just this really normalized part of our day-to-day. It's not really regulated. There are no alcohol warnings, there's no pictures of what your lungs will look like if you smoke or what your liver will look like if you drink on the canisters. So, I think there's just not as much regulation, not as much knowledge at the general level as there should be. And I think that that's something those of us in the hepatology community and those who are interested in public health are pushing for more and more.

Dr. Scott Steele: What does treatment look like for this form of hepatitis?

Dr. Shreya Sengupta: I think numbers one through a hundred for treatment of alcohol-associated hepatitis is abstinence. You're not really going to get anywhere without abstinence, so that's first and foremost. Treatments for alcohol-associated hepatitis, a lot of times, really, it's just what we call best supportive care. There are a lot of medications that are being looked at, but probably the one that has the most data is corticosteroids or steroids. And so, there are very clear-cut guidelines on when you should prescribe steroids for people. You have to calculate certain scores. They have to meet the criteria for severe alcohol associated hepatitis. They shouldn't be infected, they shouldn't be bleeding, they shouldn't have kidney injury. There are a lot of things they can't have in order to be eligible for steroids.

Steroids, there was a huge trial called the STOPAH trial with over a thousand patients. It was conducted in the UK. And really what that showed is that, even with steroids, you're not really changing even 90-day outcomes. You're really only changing short-term mortality, or 28 days. So even the medication that we have a decent amount of data for, it's not a silver bullet, it's not a magic cure-all.

There are some other medications, like N-Acetylcysteine, that are used for basically the antidote for Tylenol toxicity or Tylenol overdose. Using that along with prednisone or steroids has some role. There are some medications that are used to promote liver regeneration, like G-CSF, or granulocyte colony-stimulating factor, that have mixed data out there that people are using. That's what exists now for treatment.

Dr. Scott Steele: Can you give me a little timeline on this? Is it potentially recoverable completely, or do you always just lose a little bit of liver function and can be completely reversed? What does that look like?

Dr. Shreya Sengupta: Yeah, I think it depends on the stage of disease you're presenting with. So, how bad is it when you come to medical attention? And I think it also depends on how much injury there has been going into the episode of alcohol-associated hepatitis. So, the idea is that you really have to have been consuming alcohol pretty routinely for about five years to get alcohol-associated liver disease, but that as little as six months of pretty intense drinking can get you there.

So, I think it depends. Are you coming in with alcohol-associated hepatitis after a lifelong of heavy alcohol consumption, so there's alcohol-related cirrhosis because if that's the case, your risk of not recovering is high. And even if you do recover, you're not going back to the baseline of a normal liver; there's a diseased liver under there.

If you're coming in as someone who, and we see a fair bit of this, people who drink regularly, have jobs, have families, have never had a DUI, have never had consequences related to alcohol, but are coming in because they don't realize that they're exceeding that 60-gram daily limit. For some of those folks, abstinence and supportive care can get them back to a completely normal liver. But one thing to remember is that even people who come in with moderate alcohol-associated hepatitis, though they have a survival at 30 days of greater than 90 percent, within the next six months, about 10 percent of them will go on to develop worsening liver disease with complications including death. This is really the most aggressive form of alcohol-associated injury. So, recovery is possible, back to a normal baseline, but not for everyone.

Dr. Scott Steele: Let's reverse it. And I'm not even sure you can answer this question, but how long can you live with alcohol-associated hepatitis? Or maybe asked in another way, is it going to shorten your lifespan?

Dr. Shreya Sengupta: Yeah, we always think of everything in terms of three-month mortality. That's like the MELD score and all of these other scores we have in the world of hepatology. So, someone coming in with severe alcohol-associated hepatitis, meeting a certain criterion based on labs, et cetera, they have a one-month mortality of up to 50 percent. So, there's a 50 percent chance of dying in one month from alcohol-associated hepatitis. So how long can you live with it? With the liver inflamed that way, the risk of mortality is very high. The liver can recover. It's to some degree a forgiving organ, as long as the damage isn't too far gone.

So even over six weeks, you can see the amount of fat in the liver going away. Over longer periods of time, you can see the inflammation going away. So, I've had people who've come in with severe alcohol-associated hepatitis who I'm seeing a year or two later who are doing well, but the key there is absolute abstinence.

Dr. Scott Steele: Let's step back very quickly and maybe ask a couple of other quick questions. We hear all the time, oh, you should have a glass of wine or a couple glasses of wine. It's good for your health and heart health. And we hear all about this, but are there certain people that are just more prone to alcohol-induced hepatitis? And if I'm a person listening out there, and I come home and have a glass of scotch every night or something like that, should I stop doing that? How does that fit into this?

Dr. Shreya Sengupta: And I think those are really good questions, and I think that's why it's so hard to counsel people, and there's no one number that's a safe amount of alcohol to drink. I think it really is pretty dependent. I think women are at much higher risk than men. And I think that's one thing we'll say. So, the absolute number of cases of alcohol-related liver disease are definitely higher in men, but the numbers are increasing at pretty alarming rates in women.

I think people who binge-drink, sometimes people will think, oh, I don't have a drink every day, I just have fun on the weekends, probably binge-drinking is worse maybe than daily drinking. If you have other types of liver disease, you know, a fair amount of the population is obese, has risk factors for non-alcoholic fatty liver disease or non-alcohol-related fatty liver disease, probably there. If you have a certain amount of inflammation or scarring in the liver, probably no amount of alcohol is safe. And then family history. If you look at your family and you see there's a lot of people with alcohol-related issues, alcohol use disorder, liver disease of unclear origins, you may want to take a step back and think, maybe this nightly drink isn't the right step for me.

Dr. Scott Steele: Are there any new things on the horizon when it comes to diagnosing or treating alcohol-associated hepatitis?

Dr. Shreya Sengupta: Yeah, I think for treatment, this is a really exciting area of medicine in that there's a lot of potential. I just did a quick clinical trials.gov search using alcohol, alcoholic hepatitis, and alcohol-associated hepatitis, and I think I got 106 hits. So, that's how many clinical trials are registered about this disease process. And so, there are some pretty interesting therapies out there, including fecal transplant, to help with the microbiome. There are different nutritional supplements. And then there's novel medications, one in particular called Larsucosterol which is being studied in phase two clinical trials. And then ongoing research about steroids, GCSF, and other medications that are FDA-approved for other indications. So, hopefully in the short term/near term, there will be more medical options just beyond steroids.

Dr. Scott Steele: Now it's time for our quick hitters, a chance to get to know you a little bit better. So first of all, what is your favorite food?

Dr. Shreya Sengupta: Oh, favorite food is tough, but I think I'd have to probably say sushi.

Dr. Scott Steele: Fantastic. And what is your favorite sport to watch and/or play?

Dr. Shreya Sengupta: Favorite sport to watch, hands down, is soccer. I could probably watch that World Cup final a hundred times and never get bored of it. And then, I can't play soccer to save my life, so my favorite sport to play would be tennis, but also poorly.

Dr. Scott Steele: And bucket list trip you want to go to, or you've heard about, or you've been to, and you got to tell our listeners go there. Where is it?

Dr. Shreya Sengupta: Bucket list place to go is New Zealand. Haven't been there, would love to go there. A place that I have been that was amazing was South Africa. I went there for my honeymoon, the best trip of my life. I recommend it to everyone.

Dr. Scott Steele: And finally, although you've lived in some inferior places around there, why don't you tell us something that you like about living here in Northeast Ohio?

Dr. Shreya Sengupta: Oh, Cleveland, the ease of life here is so incredible. And I never really realized before I had kids just how much parks matter and how many parks there are in Northeast Ohio. It's been a lifesaver with my very active toddlers having options to get out of the house and get there quickly.

Dr. Scott Steele: What's a final take-home message for our listeners about alcohol-associated hepatitis?

Dr. Shreya Sengupta: Yeah, I think alcohol-associated hepatitis, in terms of all of the potential damaging side effects of alcohol, is still relatively rare but pretty serious and can be very deadly. And I think really at the end of the day, if there's one message that you get from this talk is that really there is probably no safe amount of alcohol that we've been able to define. Everyone has their own risk, and probably at the end of the day, less is more.

Dr. Scott Steele: That's great, sage advice. And to learn more about digestive disease care at the Cleveland Clinic, please visit clevelandclinic.org/digestive. That's clevelandclinic.org/digestive. You can also call us at (216) 444-7000. That's (216) 444-7000. Dr. Sengupta, thanks so much for joining us on Butts and Guts.

Dr. Shreya Sengupta: Thank you.

Dr. Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts and Guts.