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Time Stamps

  • 01:42 Intro
  • 04:37 Pearl 1: Diagnosis
  • 13:20 Pearl 2: Differential & Treatment
  • 20:48 Pearl 3: Nutrition & Alcohol Cessation
  • 27:45 Pearl 4: To steroids or to not steroids?!
  • 35:34 Pearl 5: Throwback


Show Notes

There has been a significant uptick in alcohol use and alcohol-associated liver disease during the pandemic.

Pearl 1: How do you diagnose alcoholic hepatitis? Why is this important?

  • Diagnosis is usually made by clinical history and laboratory values
    • Typically with long history of drinking (e.g. 10+ years), with usually increase alcohol consumption over last 3-6 months
    • Symptoms often vague but may present with anorexia, malaise.
      • Patients usually jaundiced
        • Onset of jaundice within 60 days of heavy alcohol consumption for a minimum of 6 months
    • Patients with cirrhosis can present with acute on chronic liver failure (e.g. hepatic encephalopathy, variceal hemorrhage, increase in ascites, AKI)  
    • Moderately elevated AST, ALT
      • Typically less than 300 -400U/L
    • AST/ALT ratio > 1.5-2/1
    • Serum Bilirubin >3 mg/dL
  • Alcohol-associated hepatitis is an immune-mediated reaction that is multifactorial. 
    • There is an initial direct insult to the liver by alcohol which leads to the recruitment of inflammatory cells. 
    • Alcohol also leads to disruption of the gut barrier which leads to bacterial translocation and inflammation.
    •  This is why symptoms can often be delayed by 2 months from heavy drinking until presentation.
  • Patients with history of gastric bypass are at higher risk for developing alcohol-associated hepatitis.
  • Other risk factors

Pearl 2: Differential Diagnosis and Workup

  • What other things should you consider in your differential diagnosis?
    • When diagnosing, should exclude other causes:
      • Anti-hepatitis A IgM
      • Hepatitis B surface antigen, anti-hepatitis B core IgM
      • Anti-hepatitis C virus (HCV) antibodies
      • Drug screen including serum acetaminophen levels
      • Biliary obstruction or Budd-Chiari syndrome using transabdominal ultrasound
  • True list of differential is much longer but should be considered based on patient demographics (e.g. HELLP, AFLP, DRESS, Autoimmune Hepatitis).
    • DILI is also considered but is a diagnosis of exclusion so labs should be ordered regardless.  
  • Workup should also include ruling out infection including blood cultures, urine cultures, CXR, peritoneal fluid studies and culture if appropriate since a large portion of patients with alcohol-associated hepatitis will die from infection.

Pearl 3: Nutrition and Alcohol Cessation

Alcohol cessation and nutrition are interventions most linked to improved mortality

Pearl 4: Prognostication and steroids

  • MELD score is the best indicator at this point and has been used more commonly to risk stratify patients with Alcohol associated hepatitis. 
  • Maddrey Discriminate Function is used to decide use of steroids.
    • Can only deem high risk vs low risk
    • Score >32 indicates poor prognosis 
  • Steroids or nah?
    • Of note, mortality from AAH has not improved over the past decades. About one in 5 patients will die in 6 months.
    • Steroids:
      • STOPAH trial is probably the most cited trial.
        • RCT Evaluated both prednisilone and PTX. Prednisolone was associated with nonsignificant mortality benefit at 28 days but no benefit at 90 days or 1 year.
      • Mild forms can be treated conservatively
        • (MDF < 32 or MELD < 20).
      • More severe forms consider treatment
        • (MDF > 32 or MELD > 20).
      • Usual course of treatment is ~28 days followed by taper.
      • Can use Lille score to see if steroids are improving and can help guide early termination of steroids.
        • Initial model used 7 days but 4 day score can also be used.
      • If steroids will be used, infection must first be ruled out. 
      • Diagnosis of an infection at the time of presentation does not mean that steroids can never be used – the infection just needs to be under control prior to starting them. 
      • There is no data to support immediate use of steroids.
        • Delaying steroids for a few days won’t harm the patient but starting them hastily may cause problems. Steroids are often not started in the presence of AKI either.
      • Cochrane review of 721 patients concluded that glucocorticosteroids did not statistically reduce mortality but there was a trend toward benefit. 
  • Pentoxyfyline
    • Older studies showed possible benefit but STOPAH trial showed no mortality benefit.
  • NAC:
    • Some consideration for use of NAC; can be used in some patients as studies showed a trend toward significance but overall mainstay of treatment is nutrition +/- steroids.
  • Liver transplant is an option but an ethical dilemma because alcohol associated hepatitis implies recent drinking which usually precludes transplant.
      • Some centers will perform transplant in highly selective patients with AAH.

Pearl 5: Throwback

  • Throwback pearl? How do you treat EtOH use disorder?
    • Supportive care should be offered to everyone including peer support groups, 12-step groups, and psychiatric support and counseling. 
    • Medications
      • First line
        • Naltrexone – One of the most effective meds for AUD. NNT is 12. Traditionally taught to avoid in cirrhosis due to hepatotoxicity though data is emerging that it can be safely given in patients with alcohol liver disease. Many argue that the risk of ongoing drinking outweighs the theoretical risk of liver injury and one study found decrease in liver enzymes with naltrexone (through abstinence)
        • Acamprosate – has not been studied in patients with lvier disease but is thought to be safe because does not undergo hepatic metabolism. 
      • Second line 
        • Topamax and gabapentin – Their well-known side effect profiles (including memory impairment and somnolence, respectively) at the doses required to achieve efficacy may hinder their broader use in the outpatient setting.
        • Baclofen – individual studies have shown effectiveness compared with placebo in reducing alcohol intake and increasing abstinence rate among patients with alcohol use disorder and chronic liver disease. However, Cochrane review of all RCTs has not shown overall effectiveness in patients with alcohol use disorder when compared to placebo.
      • Emerging therapy


M: This is Dr. Marty Fried, Dr. Shreya Trivedi. This is the Core IM, 5 Pearls podcast bringing you 

S: High yield, evidence-based pearls.  

M: Today we are discussing one of my faaaavorite subjects in all of internal medicine – Alcohol Hepatitis.  

S: I am so excited – We wanted to give a shout out to Dr. Sean Burke, a hospitalist at Case Western as well as Dr. Indira Bhavsar-Burke (yes they are married) who is a hepatologist at Cleveland Clinic who did a ton of behind the scenes work to build this masterpiece 

M: No doubt – word up to the Drs Burke for their effort here. Shrey – I have news for you. 

S: What is that? 

M: So – we have commonly heard this illness referred as alcoholic hepatitis, which is sort of a stigmatizing title.  And there’s a push to refer to it as alcohol-associated hepatitis, which I’m totally into. In this episode our listeners will also hear us refer to it as that or as alc hep for short.  

S: Yes, that is much appreciated! And something else that I thought was interesting when making this episode is that 1 in 5 Americans report heavy alcohol use as their coping method for pandemic-related stress. 

Dr. Kavish Patidar: There’s a pandemic with alcohol associate liver disease and this is going directly linked with the pandemic with alcohol use disorder, this everything got, you know, we added fuel to the fire with COVID

S: That is Dr. Kavish Patidar, a hepatologist at Indiana University.

M: Yes – pandemic on pandemics – it’s like the inception of pandemics! So now is as good a time as ever to review alcohol use and one of its most severe complications. As you listen, quiz yourself by pausing after each of the 5 questions. 

S: Remember the more you test yourself, the deeper your learning gains. 

M: Pearl 1: Diagnosis of alcohol-associated hepatitis

S: What tests and notable history points help with the diagnosis of alcohol-associated hepatitis?

M: Pearl 2: Differential diagnosis?

S: What other etiologies should be ruled out?

M: Pearl 3: The Importance of Nutrition and Alcohol Cessation

S: Why are nutrition and alcohol cessation so critical in the treatment of alc hep?

M: Pearl 4: Steroid and Prognostication 

S: To steroid or not to steroid, THAT is the question.  

M: Pearl 5: Throwback Pearl.

S: What are the medications for alcohol use disorder?

Pearl 1: How to diagnose How do you diagnose alcoholic hepatitis? Why is this important?  

S: So let’s get started with diagnosis of alcohol-associated hepatitis. 

Dr. Elliot Tapper: The textbook definition of alcoholic hepatitis is a recent onset of jaundice with at least a total bilirubin greater than 3 … most of your patients will have a bilirubin far higher. They typically have a high AST. The AST is greater than the ALT. And if you add the AST to the ALT and it’s less than 400, then you think your patient is alcoholic hepatitis. 

S: That was Dr. Elliot Tapper, a hepatologist at the University of Michigan. 

M: Shrey – the diagnosis is something I always struggled with because I’m a guy who likes tests.  I like to know what I’m treating with some degree of confidence… and we don’t get that with alc hep. What we do have is lab patterns that are suggestive 

S: I feel you and on top of that, sometimes you get a vague story that person stopped drinking a while ago and then you are scratching your head why are they feeling crummy now and why is their bilirubin AST/ALT all of a suddenly up now. 

Dr. Kavish Patidar:  And they need to have onset of jaundice within eight weeks of their last drink. So they can be drinking all the way up until your presentation or maybe two months prior their present their last drink was.

S: And I’ve always found this so perplexing and couldn’t help but wonder WHY someone’s last drink could be a while ago and but they develop jaundice and LFT abnormalities weeks to months later

Dr. Kavish Patidar: Good question. Alcohol Associated hepatitis is an immune reaction to what’s going on. So the pathophysiology, when you think about it, one, you have direct insult and then once the liver gets damaged, it’s the, these dead tissue then recruit inflammatory cells, uh, to come to the liver. hat can lead to further damage then. Then finally in the gut, alcohol actually disrupts the tight junctions within, within the gut, these tight junctions get loose, bacteria and its products, can go into the portal vein the immune cells in the hepatocytes, you know, typically Kupffer cells will run, recognize this, and again, recruit more inflammatory cells to come in and cause damage. So really, you know, alcohol associated, hepatitis it’s an  immune mediated syndrome, and, and hence, that’s why we use anti-inflammatory agents to control the inflammation in the liver.  

S: Nice so alc hep has some complex patho phys but bottom line is that alc hep is an immune reaction to alcohol, and that  inflammatory reaction can be a while — 2 months or so to be precise for all the immune cells to gather its troops and  travel to all the places to wreak havoc   

M: Ah, that is so interesting, and sort of frustrating – but it raises a good question. How much alcohol is too much alcohol?  

Dr. Elliot Tapper: The first is to say it takes a ton of alcohol to cause alcohol-associated cirrhosis or hepatitis. And if that’s what your patient has, they were drinking too much for them.  

Dr. Kavish Patidar: In a nutshell, you need the alcohol content we talked about. So more than, uh, 40 grams per day for a female, and then more than 60 grams per day for a male for greater than six months.

M: OK so if a standard drink is 14g of alcohol that equals 3 drinks per day for women and roughly 4 standard drinks a day for men — that is actually less alcohol than I would have expected.

S: Well maybe its not the amount of alcohol as much but its that amount of alcohol was persistent overtime for 6 months or so, and that persistent insult is causing that inflammation response… but I’ve seen such variable stories and timelines.

Dr. Elliot Tapper: And I think will come to this condition through a variety of pathways. One is definitely going to be new onset, binge drinking with an abrupt increase in the amount of alcohol. That is a sure fire way to develop alcoholic hepatitis number two is that you will have people who have   consistent amounts of alcohol, but it is now extra toxic to their liver. In one case, I can’t really explain why that would happen, but it does. And then the other, what you’ll see is that people will start to feel more depressed or they’ll get sick and they’ll start eating less. And because they’re eating less, they become more malnourished and then quantity for quantity that alcohol is more toxic to their body.  

S: We will talk a lot more about malnutrition in pearl 3. And with those variable patient presentations in mind, Dr. Tapper had some really good pointers for what some high yield questions he asks when he initially is learning someone’s story

Dr. Elliot Tapper: I know that they’re drinking a lot, so it doesn’t matter to me to pin down the precise amount of alcohol. I’m really interested in what was happening over the last few months. And what you’ll start to learn is one, what were some of the triggers that led them to particularly risky drinking. Two, how depleted they are nutritionally. And then three, you’ll get a sense of some of the other things that they were using, the alcohol to cope with. It could be dental pain, and they’ll have comorbid abscesses and all kinds of things that are gonna be super important. As you decide on your therapeutic strategy.

S: Ugh so much good stuff in there but I wanna highlight understanding more the triggers and habits associated with drinking with a view towards the future and prevention

M: Yep, I also want to shout out that Dr. Tapper doesn’t spend so much time nailing down the precise amount  of alcohol consumed  – but when we sat down with the hepatologists we learned was that there are certain populations at higher risk for alc hep.  And this sort of resonate for me because I’ve seen plenty of patients who develop alc hep but they don’t fit the bill of 3 or 4 drinks a day for the last 6 months.

Dr. Elliot Tapper: Now, there are certain people that can get sick with less amounts of alcohol. Typically these are biological females and two those with gastric surgery. So gastric sleeve, Roux-En-Y bypass. These are highway tickets to alcohol hepatitis.

M: Ok so patient with a higher risk of alc hep are going to be those assigned female at birth and s/p bariatric surgery – any ideas  why alcohol has such a higher impact on those patients?

S: So, it’s thought that after bariatric surgeries the same amount of alcohol results in higher peak blood alcohol level and it takes more time to eliminate that alcohol. And to put some numbers to it, one study found that for women with roux en y bypass, drinking 2 beers actually ressembed the blood alcohol concentration that you would expect after 4 drinks. And some of this is thought to be due to bypass of gastric alcohol dehydrogenase.

M: Ya know Shrey – that alcohol dehydrogenase… if I had a nickel for every time someone mentioned alcohol dehydrogenase.

S: Hahah oh gosh, it similarly rears its head with the whole females being at risk so females may have are at higher risk because of differences in how hepatic alcohol dehydrogenase is distributed and differences in body compositions

M: This is all good food for thought because there are some patients who drink so much and never develop alc hep but then other patients who drink much less than them and develop disease – and your like this is such an injustice!

S: Very unfair! So is definitely a component of genetic risk.  

Dr. Kavish Patidar: So, you know, a lot of this has to be of this a genetic strong genetic component to this that primes them, and then you get a secondary insult, which is alcohol  

S: Again, almost a relief to hear to give some reason why it happens to some and not others.  Marty, do you want to recap for us?

M: Would be my pleasure Dr. Trivedi. So the diagnosis is alc hep is often a clinical diagnosis, usually having the classic AST/ALT pattern with elevated bilirubin higher than 3 in the setting of a recent  significant alcohol exposure, usually within 2 months of their last drink. Since alc hep is an immune response, these patients will often have vague complaints of malaise and anorexia.  And be wary of the bariatric surgery patients because they may end up with TWICE the blood levels of alcohol for any given amount of consumption.  Most importantly when you see these patients don’t forget to ask about their drinking triggers which will help you a ton down the road when it comes to long-term prevention. 

Pearl 2: Differential Diagnosis and Workup

S: Ok so say we have a patient that presents with significant drinking history with Tbili 14 as well as elevated liver enzymes that aren’t over 400. Case closed? No?  What else should we be thinking about?

Dr. Elliot Tapper: It is incumbent upon you to broaden your mindset and not have premature closure on one possible thing when your patient has very high liver enzymes. Because in fact, Tylenol toxicity can kill your patient faster than alcoholic hepatitis as can a stone in the common bile duct. Yet, you will meet people that might fit the bill and they have a very high AST/ALT. Yes, they might have alcohol related injury, but they could also have drug-induced liver injury from   medications, supplements, or illicit drugs that have been used. They could have acute viral hepatitis.

M: Sounds like they can have choice E, all of the above? 

Dr. Elliot Tapper: A patient can have both alcohol hepatitis and Tylenol toxicity, acute viral hepatitis, or a stone in their common bile duct. So they are entitled to break that rule.

M: And that rule that patients are allowed to break here is that the AST and ALT levels are typically less than 400. IF we have lots of things going on they are entitled to shoot those ASTs and ALTs all the way up. 

Dr. Kavish Patidar: So making sure they don’t have a  mass in their liver or a big, uh, portal vein  thrombosis, which can lead to very similar clinical pictures. 

S:  There may be some other things to consider like  autoimmune hepatitis, Wilson’s or if a pregnant  thinking of HELLP,  acute fatty liver of pregnancy, OR If you find yourself stranded on a standardized test question, naturally Mushroom poisoning.

M: Gotta watch out for that Death CAPPPPPP!!!! 

S: Apparently… and we should not forgot the most important thing we should be assessing for.

Dr. Elliot Tapper: Your patient with alcoholic hepatitis has about a 20% chance of dying from their disease and what are they going to die from? They might die from bleeding or renal failure, but more often than not, they will be dying from infections. So when I see a patient with alcoholic hepatitis, I put a li- I shine a light in their mouth. I look at their legs, the back of their legs, the front of their legs for cellulitis, for puncture wounds. And I’m constantly searching for, uh, a potential cause of something that could lead to sepsis. It is not unheard of for patients that I admit to have dental extractions during their hospitalization for abscess teeth. It is extremely common that patients will go on to develop bacteremia from even the smallest seeming sources of cellulitis. So I’m constantly scared of the possibility of missing an infection in my patients, from things that might seem benign to you in others.

M: Both our peer reviewers wanted to emphasize to please, please get that diagnostic paracentesis on any admitted patient with ascites regardless of the white cell count or an absence fever or absence of pain!

S: Yes to the paracentesis! But I just want to point out how tough it can be from a ddx because a lot of these patients will meet SIRS criteria but no obvious infection is found and a humbling reminder that not all that SIRS is sepsis. 

Dr. Elliot Tapper: At the same time, the alcohol toxicity makes the immune response more unrestrained. There’s less of a lid to put on the immune response. So you’re all SIRS and, uh, nothing to tamp that down.

S: I feel that – these patients can be really sick, and being “all SIRS” is pretty much always going to make me nervous, infection or not

M: And the other tough place we find ourselves  is thinking if this acute alcohol-associated hepatitis or is this just their cirrhosis worsening in front our eyes

Dr. Kavish Patidar: So, you know, alcohol associated liver disease is a spectrum. So you have hepatic steatosis then you have alcohol associated hepatitis, which is severe form, um, acute and chronic liver failure type form. And then you have alcohol associated cirrhosis. Now you can have to make complicate things. You can have alcohol, uh, alcohol associate hepatitis on cirrhosis. 

S: Yeah so I really pushed the hepatologist on this. And to normalize just how hard it is, Dr. Tapper told me about a patient he saw in clinic way back during his intern year.

Dr. Elliot Tapper: He hadn’t had a doctor for many, many years, and I noticed that he had decompensated cirrhosis that he had jaundice. And when I got the labs back after I’d gone home, I realized I forgot to get an INR to do a discriminating function, but because his bilirubin  was high and he reported to me excessive alcohol use, I sent him to the emergency department to get an INR. And if it was high, we could potentially start steroids. But after the dust settled and I had a therapy session with the consulting hepatologist, I came to the realization that we just didn’t know his trajectory. It was new to me. But if you asked, he’s been sick for a very long time and it was the judgment that this was progressive liver dysfunction, just based on the gestalt of the clinicians who had seen him. So to answer your question, there is no rule, uh, by which we can distinguish these two things.

S: I really appreciated hearing that bc sometimes especially when you get down to your assessment section of your H&P… gosh this person drinks alcohol regularly, was what they drink enough to acute this acute inflammatory insult to their liver or is it just their cirrhosis getting worse

Dr. Elliot Tapper: If I had thought clearly, it was clear that he was sick and it was, but he was presenting to me with an illness that had not gone away. He was presenting because of edema and ascites that had been lasting a few months. And the jaundice was really an incidental chronic feature of his presentation. And it was correct in the end to not try corticosteroids

M: So it sounds like we need to understand who this patient was in the past and just think about, does this looks and feels like a new inflammatory state vs a more chronic progressively worsening. May I echo the desire now for a single diagnostic test.  

S: Yes, I hear that.  Let me just wrap up what we are hearing so far. The diagnosis of alc hep requires you to  send off Hep A, B, C, serum acetaminophen level, for imaging RUQ US with doppler to r.o biliary obstruction or even thrombus or cancer in the hepatic or portal vein. Also, look for infection, yes the standard CXR, BCx UA and diagnostic paracentesis if needed but also everyday do a good skin exam and look in the mouths, look at those tushes and ask about tooth pain!  All of the above. 

Pearl 3: Nutrition and Alcohol Cessation: Alcohol cessation: 

S: On to treatment, after talking to Dr. Tapper and Patidar I’ve really changed my practice on what I focus on with patients – 

M: YES.  FINALLY.  This is the part of the podcast where we get to talk the age old pred vs pentox and maybe we’ll throw in a Lille score for lactulose and giggles, right? 

S: Wellll not quite. What if I told you there is something even more imp than pentoxifylline and prednisone?

M: More important?

S: So its actually nutrition and alcohol cessation. First on deck, let’s tackle nutrition.

Dr. Elliot Tapper: Nutrition is the first line therapy in the management of alcoholic hepatitis. And typically what we are doing is we’re trying to make them eat dense high calorie enriched foods, the entire time that they’re with us. This involves at a minimum, making sure that they have snacks at night and hopefully between meals. The people who are most likely to die from this condition are those who are not meeting nutritional goals.

S: A cool pathophys pearl that I learned about why these patients are so malnourished,  is in addition to much of their caloric intake coming from alcohol is that alcohol actually gets metabolized first and then impairs the absorption and digestion of other macro and micronutrients! So alcohol is just a big bully in the gut.

M: The biggest bully! OK so we know why they are malnourished.  I’m guessing the next steps are, like feeding them, right? 

S: Yes and I love how Dr. Tapper has a honest conversation upfront about the trajectory of Alc help and the possibility of  nasojejunal feeds.

Dr. Elliot Tapper: But what you have to do is begin from the beginning, which is to say they are very sick. They’re at very high risk of dying. The only thing that is gonna keep them alive right now is time to recover. And the only thing that will allow them that time is freedom from infection and, and nutritional support. So, because those are only two tools that we know are truly proven to save their lives. We have to meet those goals. So I will start out slow. What would you like to eat? If I can get rid of sodium restriction to help the patient, I will do that. If their family wants to bring in food, let ’em do that. If they want to eat nothing but boost or ensure, let them do that. But after meeting a, after setting a goal, failure to meet that goal in the next couple of days should be paired with an honest discussion about the role of tube to save their life.

S: I have to say in any other patient population on the floors, I try to avoid the NJ tube as much – it can be so uncomfortable for patients, but after hearing Dr. Tapper I am sold and like okay we gotta do this, give me the lube!

M: Shreya is now one  with the NG – what did Dr. Patidar or Tapper say about how much we should be feeding our patients with alc hep?

Dr. Elliot Tapper: So the calorie count that I want for this patient is something like 30 kilocalories per kilogram, per day. And then I wanna make sure that before they go to bed, they’re having a snack that has something like 2-300 calories and some protein in it. Uh, so that they have that. And they’re not fasting overnight.

S: Just want to emphasize that a good amount of those calories should be protein. So I’ll ask my patients to order that chicken and greek yogurt.

Dr. Kavish Patidar:Going back to pathophysiology, why is nutrition important? So whenever you’re in a starvation state, you, your lining of your gut on top of alcohol causes even more disintegration of your gut barrier. By keeping your gut alive by giving it nutrition, um, can help alleviate this part of the pathophysiology  

S: Powerful to think about. Keep the gut lining together with nutrition. This is a pretty vicious cycle. These liver injuries cause an extreme catabolic states and that increased energy expenditure only worsens that malnutrition.   

M: ok – so big moral of the story is not to overlook nutrition.    

S: Right and the  second critical pillar for treatment for alc hep is addressing the underlying issue – drinking.    

Dr. Elliot Tapper: Remember this person has liver disease because of alcohol use disorder. So while this person is in the hospital, it is a critical time to discuss with them relapse prevention. This is in your wheelhouse. It is not something to be deferred to the outpatient setting and every extra step that you can go talking to the patient, talking to somebody that they’re friends with to help them get a ride to the relapse prevention, prescribing the pharmacotherapy that they can use as a bridge when they get home. All of these things are well within your power.  

M: And props to Dr. Tapper for encouraging us to start medications for AUD in the hospital, and you better believe we’re going to talk more about that in just a moment for the Throwback the alcohol use treatment episode in Pearl 5  

S: But Marty this makes me reflect on how we put in a social worker consult and then the patients may get a list of alcohol cessation resources and a part of me always wonders if that’s enough but I get too busy on the next task or next page but I appreciated how Dr. Tapper challenged us to be an extra touch point – say for example on the next day on rounds.

Dr. Elliot Tapper: So closing the loop, what did you think about that? Which of these locations works for you? Is there somebody who’s off work and can take you at that time? All of that is reasonable. All of these things are gonna be helpful.  

M: So why don’t we recap the REAL treatment for alc hep. Its going to be making sure they are getting adequate calories, which is 30 kilocalories per kg per day. And run towards the alcohol use!  Take an alcohol use history to prepare patients for success after discharge and whenever possible link them to treatment, which can be meds or groups or counseling – the extra nudge is for sure worth the effort.   

S: And one last extra nudge from Dr. Tapper  

Dr. Elliot Tapper:  I am desperately asking you to make sure that there’s extra snacks on that patient’s table and that somebody is counting how many calories they’re eating.  

Pearl 4: Prognostication and steriods  How do you prognosticate? 

S: Let’s talk about steroids for a second.   

M: Yep – enter, STOP-AH.   

Dr. Elliot Tapper: The broadest, most rigorous evidence-based for it is from a trial published several years ago now called STOP-AH  or Stopa. And this is a two by two factorial trial that looked at prednisone and Pentoxyfiline and placebo. It’s why we know that pentoxifylline does not work. And in that trial, prednisone was associated with improved 28 day survival, but not 90 day survival. So this means it’s not a parachute. This means it is not necessary for us to use.  

M: That is a subtle but very important learning point regarding steroids. They have shown an overall trend in mortality, but we have to remember that steroids are not silver bullets.   

S: So classically the very simplified teaching is to* consider* about steroids (and with emphasis on the word is CONSIDER   for patients with high Maddrey’s discriminant function of >32   

M: Any thoughts on using MELD here  

S: Right so a new teaching for me but MELD is coming more to the forefront as the better prognostic score and you could consider starting steroids for a MELD >20    

M: But which score (MELD OR Maddrey’s) we’re using I always seem to myself torn about starting steroids.  Like, are they not sick enough – too sick?  What I found comforting was that both hepatologists we interviewed emphasized the importance of not rushing to start the steroids.   

Dr. Elliot Tapper: Take a step back and realize that there is no time to prednisone metric that you’re being judged by. Now, if you wait two days and the patient still is sick, or their bilirubin is rising and you feel like the prednisone me makes even a greater difference. Now, then you haven’t hurt that patient. The benefit from that prednisone has not been reduced. So do not rush this. If you never gave that patient prednisone at all, you are not hurting that patient. This is, these are marginal changes in 28 day outcomes. So don’t beat yourself up so much about this, take it slow, don’t overdo it.  

S: Wow I wish I had heard this years ago!  And if most of these patients dying from infection – in alc hep,  steroids can be doing real harm  

M: Yeah so if there was an initial concern of  infection like pneumonia when can you start steriods if they is indicated?

Dr. Elliot Taper: 10 outta 10 hepatologists agree that you at least have to have the infection under control. So you’ve started antibiotics and you’ve seen that the patient is at least stable before you start to think about prednisone. So this applies to pneumonia, urinary tract infection, SVP, bacteriuria, all of that.

Dr. Kavish Patidar: But if they get acute, if they get sicker, at that point, you have to stop steroids. Um, you know, infection is what’s gonna take their lives at that point  

M:  Ok – so IF I’m actually pulling the trigger on starting steroids in a patient with alc hep – which is honestly a little tough to do – but here we are – What about which steroid to use? This is a classic teaching point that we often hear being thrown around. 

Dr. Kavish Patidar: We give prednisolone not prednisone, uh, because, uh, prednisone has to be converted to prednisolone. And that happens in the liver… the liver is sick, it’s not gonna do that.  

S: Yes and I may have said this myself too before but turns out this is just theoretical and MedEd trivia. Honestly prednisolone is something we do because thats whats been used in landmark trials but in practice prednisone and prednisolone have similar efficacy. And if you want some cool pathophys backing, know that the enzyme that’s in the liver converting prednisone to prednisolone is also found in muscle and fat and that can help!  

M:Wow Shrey, we can just start calling ourselves the CoreIM Myth Busting team. So if we start steroids, how many patients do we expect to respond? And are there certain patients more likely to respond?   

Dr. Kavish Patidar: Um, and so we know also now that about, only about maybe 40 to 50, 40 to 60% and will actually respond to steroids  

Dr. Elliot Tapper: The people  who I think are most likely to benefit are those who are young, who are women. And I see that the alcohol trajectory is relatively compressed within the last year or two. That’s where my gestalt tells me I’ve got a more resolvable reversible condition.  

M: Ok so we have plus or minus a coin flip on response rate, and I’m prioritizing steroids for younger women and patients with a recent alcohol history.   

S: RIGHT BUT this is NOT a set-it-and-forget-it type of intervention…

Dr. Kavish Patidar: The Lille score when it  first arrived, look at day seven, uh, changes from your baseline to your, to your day seven labs. So a couple of single centers that looked at day four little score, and what they found that day four little score works just as well as day six, seven.. but one caveat to that study was it had very large confidence intervals. Um, so, um, you know, you have to put the whole clinical picture into it.   

Dr. Elliot Tapper: What I do is I start it and I follow that bilirubin, if the bilirubin doesn’t fall by day four, we’re done that, that pre, that person is not gonna benefit from the prednisone, not this is best articulated by the Lille score, which is just basically watching the bilirubin fall, but having a formal calculator to put in the chart for that. And I made that decision in 4 days.  

S: I love it. Now I like to arm myself with some numbers that makes it easier for my brain to translate that Lille score actually means and help me communicate it to patients  

Dr. Kavish Patidar: A score less than 0.45 indicates a good response to steroids. And the patient has greater than 80% chance of surviving at six months. If the score is greater than 0.45 than, uh, they’re not responding to steroids, and you need to stop. And, and at that point, their survival is, you know, maybe 20% at six months now.

M: Wow that’s a pretty shocking survival difference –  80% vs 20% based on bilirubin trend.  Wow.    

S: Well Dr. Paditar did have a caveat to the Lille score and that’s just how age gets factored into Lille score  

Dr. Kavish Patidar: I would say one Pearl that I’ve been, that’s been passed down to me is sometimes because of age factors into it, sometimes a Lille score will be unfavorable, but you’re looking at the bilirubin and it’s like, oh my God, it’s actually decreased by 40% in these patients, you can consider continuing, you could consider continuing steroids long as they have close follow up where you can get labs, making sure they’re not getting sick or infected  

M: Okay, so especially with older patients interpret the Lille score with a grain of salt and potentially look at their bilirubin independently.  If a patient who is older has significant improvement in bilirubin, it may be reasonable to continue steroids despite a Lille score > 0.45  

M:  Alright Shrey – It’s time to wrap this one up?  

S: Absolutely! We typically consider steroids with MDF>32 or MELD >20. It’s really the bilirubin that is the most important prognostic test which drives Lille score, which helps you at day 4 and day 7 make a better judgment if the steroids are helping and if you should continue for the 28 day course or if you should stop it. Most important takeaway for me from this section is there is no rush to start steroids and you really want to be sure infection is ruled out or under control.

Pearl 5: Throwback

M: So for this pearl, we have a throwback pearl all the way back to 2018 on  treatment of alcohol use disorder. We were thinking we would just replay the whole episode for you at 3x speed.  

S: … I don’t know if that is a good idea.  

M: For sure – so, to start, we know that overall we do a very bad job at prescribing pharmacotherapy to decrease alcohol cravings.  

S: Yeah there was actually a recent study of 35000 patients with cirrhosis and I was surprised to see that less than 2% were started on for medical treatment of the AUD… Talk about room for improvement!  

M: So with that, let’s get into the meds. The first-line pharmacotherapies for moderate to severe AUD include naltrexone and acamprosate.    

S: Naltrexone is thought to work on the reward pathway to blunt that anticipatory excitement that people with AUD typically experience just before drinking. I tell patients all the time there is a NNT of 12 to prevent returning to heavy drinking with naltrexone  

M: Yeah a powerful response rate indeed, now can we use it in patients with cirrhosis? This seems a bit controversial since its been hammed to use caution in severe liver disease but there was fairly unanimous agreement  by our hepatologist reviewers and interviewees  about using naltrexone even in patients with severe but stable liver disease, which was definitely a learning point for me.   

S: Yes I was surprised to hear hepatologist have been using naltrexone in patients with cirrhosis but maybe we overstate the caution since risk of NOT treating their AUD and drinking relapse typically outweighs the very theoretical risk of elevated transaminases.  Of course robust data for this is evolving. I think the big takeaway for me is to focus on the other things that  so maybe the real contraindications to naltrexone, which is 1) concurrent opioid use so always good to ask your patients if they using drugs or may plan to in the future 2) avoiding naltrexone if they are at risk of DTs in the outpatient setting since naltrexone can be so effective. On to the second first line option… Acamporsate is thought to reduce physical and psychological discomfort.. like sweating, anxiety and insomnia many alcohol-dependent individuals experience once they stop drinking. It usually takes 5-8 days for it to take full effect.  

M: And the other bummer is that acamprosate is 3x daily dosing, and is contraindicated in patients with creatinine clearance <30. I use both naltrexone and acamprosate fairly commonly in clinic, and it’s worth noting that BOTH meds have GI side effects – naltrexone more commonly cramps so take with food – acamprosate more commonly causes diarrhea and give patients a headsup it will get better with time.  

S: Now let’s get into second line options including topiramate and gabapentin.   

M: These meds are reasonable options, but you need to push the dose for both making their well-known side effect profiles more relevant when used for alcohol use disorder.  With this pair you’re going to counsel about cognitive fogginess.    

S: And a third option only briefly touched on in the episode was baclofen, which is the only medication that has been studied in patients with alcohol associated liver disease   

M: And there is that whole group of avante garde therapeutics including psychedelics.  Since recording our AUD episode, a recent paper was published in JAMA Psychiatry that supported the effects of Psilocybin in reducing alcohol use.   

S: Yes, this study showed that patients receiving psilocybin plus therapy reduced their heavy drinking days from 23.6% (in the control group) to about 9.7% in the intervention arm.    

M: Farrr out.  But seriously, that is super exciting.  We will wrap up with the episode with one last take away from Dr. Tapper:  

Dr. Elliot Tapper: The key take home messages about alcoholic hepatitis is one, this is a condition with a very high mortality rate. And although the hospitalizations are, can be long and there’s not much action, what happens in those day to day encounters, the connection that you make with that patient has the capacity to change their life and to save their life. And that means linking them to alcohol use disorder care and making sure that you have addressed their malnutrition, their risk of variceal bleeding and the like. Finally, I need you to be terrified that this patient has an infection. That means making sure you see their naked legs, that you’ve looked in their mouth and that you are constantly suspicious that you’re at risk of the patient sabotaging you, developing an infection in a focus where you’ve just, osculated where you’ve just looked at them. They can, you will turn your back on them and they will, they will get you. You have to be very worried about infection. So if a bilirubin suddenly spiked in the middle of the hospitalization, I am immediately thinking about infection.  

S: And with that, that is a wrap for today’s episode. If you found this episode helpful, please share with your team and colleagues.  Thank you to our peer reviewers Dr. Alyson Kaplan and Dr. Alan Bonder. Thank you to Daksh Bhatia for the audio editing and Dr. Sam Woodworth for the accompanying graphics. As always we love hearing feedback, email us at hello@coreimpodcast.com. Opinions expressed are our own and do not represent the opinions of any affiliated institutions.


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