I wanted to thank you all and the organizers for allowing me to be able to give this talk today. My name is Ashna Singh. I'm one of the transplant hepatologists, gastroenterologists at Indiana University. And this session, you know, you guys have sat through several hours in the post-grad course, which has been fantastic, of a very big room, a lot of people. I wanted this to be able to be somewhat more relaxed and a little bit more interactive as much as we can for this setting. So, all right. So, I have no disclosures and just an outline. So, during this next hour, we're going to work through three real inpatient cases. I want it to be as interactive as possible, though I know we're somewhat limited with the format. Feel free to come up to the mics and ask questions at any time. I am hearing impaired. I wear hearing aids. So, please speak into the mic if possible. And the objectives for this next hour will be to review criteria associated with acute liver injury versus acute liver failure versus acute and chronic liver failure, review common patterns of liver injury and common culprits of liver injury. And before we get started, I just want kind of by show of hands, how many in the room are learners or trainees? Okay. And how many are faculty, staff? Okay. And do we have any APPs? Excellent. Okay. And so, a lot of what you think of when you approach these patients can really be influenced by where you practice. And so, I know DDW always brings out people from everywhere. So, I wanted to get a sense of where people in the room are from. So, North America. Okay. South America. Okay. Europe. Okay. And Asia, as well as Russia. And Africa. Okay. All right. Now, many of my trainees don't know who this is. And hopefully, you guys are as old as me, if not older, know who this is, but it is important to distinguish acute liver injury from acute liver failure. Right? When I get the call from a transfer, you know, from an outside hospital or from one of our sister hospitals, really important for me to be able to triage where this patient goes, what level of care they got, whether this is truly acute liver injury or acute liver failure. So, in both instances, you will see significant abnormalities in the liver chemistries. Right? They're going to be abnormal, pretty markedly so. And you can have coagulopathy present in both, though typically many times acute liver injury will have no coagulopathy initially and only later develops. But the one big kind of distinguishing factor is that there should be no encephalopathy in acute liver injury. And in cases that do have, you know, fulminant liver failure patients, typically, that encephalopathy eventually, you know, comes about. So, within 26 to 28 weeks of presentation, many times patients don't hit the door. Right? Don't hit the hospital until they've been having these symptoms for weeks or weeks before. But really important for acute liver failure patients is that these are patients who have had no prior history of any preexisting liver disease. So, this is not the decompensated cirrhotic that now has acute on chronic liver failure, which we do get those calls. But being able to distinguish these two is important. And the rest of this talk is going to focus mostly on acute liver injury. So, what patterns of liver chemistries do I typically look for when I approach these patients? So, there is this formal R ratio that you can calculate, which is taking the ALT and dividing it by the upper limit of normal, and putting that over the alkaline phosphatase and dividing that over the upper limit of normal. And that gives you values that tell you if this is something that's more hepatocellular, a mixed picture, or a cholestatic picture. I will tell you the reality. I do not do this calculation real time clinically. And so, below it here, I've provided kind of a primer of what do those liver tests look like. So, in a hepatocellular pattern, you'll typically see AST, ALT be markedly elevated. The ALTFOS might be normal or just minimally elevated. And what's important here is the T billy is usually very low. For mixed picture patients, you'll see moderate elevations in the AST and ALT. Again, the ALTFOS may be normal, may be mildly elevated, but you'll typically see an abnormal T billy. And for cholestatic pattern patients, the AST, ALT might be a little bit elevated, but you're not going to see marked elevations, not in the hundreds or thousands. The ALTFOS is typically high, and the total billy ribbon is also high. So, on to our first case. This is Mohamed. He is 40. He is a Yemeni male with a history of metabolic syndrome who presents to the ER at the direction of his primary care for jaundice, right upper quadrant pain, and anorexia. So, 100% they're going to call GI, whether in the ER or after they admit him. And so, I want you to start thinking a little bit about the differential, which is quite broad with what I've given you. So, some more history. He presents in June, but in April, he actually started to feel badly. He had right upper quadrant pain. He had nausea, losing weight because of the nausea. And the PCP gets some basic lab tests. And you see here, the AST, ALT are pretty high. ALTFOS, not as high. And billy ribbon and INR are normal. So, very rationally, the PCP decides to stop the statin, stop anything that could be causing any injury. And he continues to check labs as an outpatient. So, these are the initial labs. And then you see that things are actually getting a little bit better. The AST, ALT are coming down. The ALTFOS has come down to totally normal. And the billy ribbon has continued to stay normal. Also, very appropriately, they check an acute viral panel. And that's all negative. And so, just kind of to go back to his time course. So, April symptoms started. May, they were all improving in terms of the liver test and the symptoms. But then he takes a downturn. And in June, starts to turn yellow. And had return of the symptoms. And so, was asked to come to the ER. So, when he comes to the ER in June, these are his new liver enzymes. So, AST, ALT have taken a marked uptick. ALTFOS, not much. But now the billy ribbon is elevated. So, he has a mixed cholestatic picture. And of course, in the ER, they do imaging. The CT scan's not very revealing. It's showing really nothing other than some maybe borderline adenopathy. And a thickened gallbladder wall. And so, they call us for a further evaluation. They do grab a lipase. And it's normal. And a liver Doppler ultrasound, which shows patent vasculature. So, what's in the differential now? And is it the same as it was before? Is pancreatitis lower down on your differential? Because you see a normal lipase. But we haven't given you much history. Does he have a history of drinking? And just hasn't owned it or been truthful about it. So, really, everything's kind of still in the mix. So, we go on to do more workup. So, do check the acute viral panel. Again, it's been a few months. So, hepatitis A and B are the only two viruses other than E that would cause such an elevation liver test. So, those are negative. His ALKFOS, I mentioned a few times. It's been borderline low to normal. And so, that does make you a little bit worried about things like Wilson disease. But his seroloplasmin is normal. We do check a hepatitis E IgM. This was the case back when I was in Michigan. And so, we do have several farms and well water areas. And so, that is a routine part of our testing. And so, that was detected. The viral tests, CMV, EBV, VZV, HSV, which you wouldn't expect to give such a marked elevation in bilirubin, were tested, but negative. Autoimmune liver panel tests were negative. Alpha 1 genetic testing, negative. His iron studies are abnormal. So, iron saturation is quite high, and the ferritin is high. But obviously, he's having an acute illness, right? So, it's an acute phase reactant as well. So, we do further testing. We do send off for the hepatitis E RNA quant, and that is negative. And then, we also check for the hemochromatosis gene testing, and that is negative. So, what do we do next? He goes for a liver biopsy. So, this, his biopsy shows moderate mixed lobular and portal inflammation, and predominantly, you know, lymphoplasmicytic inflammation. And he has interfaced hepatitis. So, this very sharply demarcated region you can see of inflammation to the regular rest of the liver. And some non-caseating granulomas. So, the pathologist equates this as autoimmune hepatitis. But this is a 40-year-old guy, and all of his autoimmune markers are negative, though they can be in about 20% of patients with autoimmune liver disease. But it leads us to kind of go back to him and talk to him some more. So, we ask him about any supplements whatsoever, which we had asked him about a few times before. But sometimes, patients kind of don't realize what is important to bring to the table and to the story. So, he actually tells us that he previously grew cot in Yemen. And that when he was there, he would frequently chew it, as well as drink cot tea. And then, once he came to the US, he continued this habit. And so, in the course of the few months that he had presented to his primary care, he had been doing his routine chewing, and then felt bad and kind of backed off for a few months. But then, started to feel better again, as we saw. Liver tests got better, and then went back to chewing it. And so, off I went to liver talks to try to figure this out. So, there is a phenomenon, cot can cause drug-induced autoimmune hepatitis. And so, that's what this gentleman had. It is a leafy green that is grown in Ethiopia, Yemen, Saudi Arabia, Uganda, and can be taken to other places to be grown, though not legally so in many countries. It is a very similar substance to methamphetamine. It's a little less strong than methamphetamine, but it has a very similar profile of kind of being an upper. Most times, cot-related injury actually causes a hepatocellular elevation in liver enzymes. So, AST, ALT predominant. But there have been cases that have been described with this cholestatic mix picture, like our patient presented with. So, take-home points for this case. Timeline is really important, and then kind of being able to track, if you can, find old liver tests and be able to take a look at them and see what they've been doing. This patient clearly had this kind of undulating pattern of liver test elevation, which makes you think autoimmune process, or could there be some repeated insult from a toxin. Eliciting a very thorough history of supplements of any kind or any kind of illicit drugs is really important. Sometimes, you know, there's stigma associated with especially illicit substances like cot, and so people are not always super forthcoming, but trying to get that information, and I think repetition, asking every time you see the patient to see if they can elicit that is important. And then liver tox is a really great resource. All right, so on to our next case. This is Mike. He is 54, has a history of alcohol use disorder, has been away from care for several years, and he comes in from an outside hospital for elevation of liver enzymes. When we ask him more questions, he says he has been told that he's had abnormal liver tests once before when he had COVID. And then in my review of systems, liver review systems, no tattoos that are homemade, no homemade piercings, no illicit drugs or IV drugs, and no supplements. Denies any blood transfusions before 1992, no new vaccines, but does admit to drinking six to seven beers a day for the last 10 years or so. And also tells us that he works for a living with sheep. He's a cattle farmer. He tells us that two weeks ago, he just started to feel so bad that he stopped drinking cold turkey. And since then, he's noticed he's turned yellow, he has nausea, he has fatigue and anorexia. So, in your differential, probably the biggest thing that's coming to the top is this must be alcohol-associated hepatitis, right, just talking to him, looking at him, and not seeing any other lab values or anything else. These other diagnoses are definitely in the mix, but acute alcohol-associated hepatitis is probably at the top for all of us. Until I see the lab work. And so, his liver tests, his AST and ALT are markedly elevated, more so than I would expect with simple alcohol-associated hepatitis. So, something else is going on. Alkfos is relatively normal, and his total billy is quite high. Albumin, acute phase reactant, so low, doesn't necessarily correlate with chronic liver disease. And then, the rest of his lab work is really unrevealing. His INR is normal, essentially. So, we get more lab testing. His PATH test is very mildly elevated, so kind of consistent with the story that he's telling us that he stopped drinking a few weeks ago because he didn't feel so good. IGG, markedly elevated, over 2600. We do check a serolopasmin. He's young, less than 55, and his alkfos was low. So, it's normal. And then, we did check for acute fever because he worked with sheep, and that was negative. So, I want to bring attention. His AST, ALT also is not in that classic two-to-one pattern that you would expect if this was alcohol-related, you know, associated hepatitis, even with knowing that this is way too high for it to be just alcohol. So, we go on to get cross-sectional imaging. So, he definitely has steatosis, right? His liver is a lot darker than that spleen. He has a relatively normal shape of the liver. It's not overly large, not nodular. There's no sponomegaly. So, we get more imaging, especially with that biliary ribbon of 18. So, MRCP is done, and we see no biliary obstruction. There's no strictures. There's no stones. And then, I do some digging. And, we find old records, not that old, but from 2020, where I do see that he's had two occasions of AST and ALT elevations. Then, they were in the hundreds. And, the ALT at that time was greater than the AST, just like with this presentation. And so, this is a list. This is not an exhaustive list, but a list of some of the things that can cause that ALT greater than AST. So, drug-induced liver injury can do this, genetic diseases like autoimmune liver disease, hemocomatosis, Wilson, alpha-1 antitrypsin deficiency, acute trauma to the liver from surgery, other things can do it. So, we did more testing. And, many of his autoimmune markers were markedly elevated. So, his antimyocardial antibody was high. His anti-smooth muscle antibody was high, though not markedly so. 1 to 64 isn't crazy high, but it's high. Ferritin elevated, but again, it could be an acute phase. And then, the iron sat was elevated at 35% right at that cutoff that we think of for hemocomatosis. So, more labs. We did get his HFE gene testing back. And, it was indeterminate, but he really only had one copy of the HFE gene. It was a heterozygous, with this copy, less than 2% of patients would ever go on to develop any clinical hemocomatosis. So, not likely. So, what did we go to next? Liver biopsy. And so, this was his final pathologic diagnosis. So, prominent lymphoplasmicytic inflammation with parenchymal collapse compatible with autoimmune hepatitis. Whenever I see that final path diagnosis, I actually kind of very quickly glance at it and then go down to the microscopic description where all the meat of what this is described. So, there's severe lymphoplasmicytic inflammation, interphase activity. That is really, those findings are very consistent with an autoimmune hepatitis. Surprisingly, there's no significant steatosis, even despite his six to seven beers a day for 10 years. And, there's no significant cholestasis, despite his bilirubin of 18. What that tells me is that he hasn't had that bilirubin of 18 for very long. And then, the most important finding for a transplant hepatologist in looking at, well, he had areas of parenchymal collapse, but there was no significant necrosis, which means his liver should recover. If you see a lot of necrosis, especially over 50%, that's when you're geared towards thinking this may be somebody who will eventually need transplant sooner than later, even if we get everything under control acutely. And, he only periportal fibrosis, which is F1, F2 at most. And, iron staining was negative. And, this just demonstrates that interphase hepatitis. So, a little bit about true autoimmune liver disease. It can present in a myriad of ways, and usually has a very undulating course. There are several diagnostic criteria, biomarkers, serum biomarkers, with an ANA, anti-smooth muscle antibody. Sometimes, you'll see correlated mitochondrial antibody elevations. That's for type 1, type 2, mostly found in pediatric patients. But, the anti-liver kidney microsomal antibody will be positive. Seeing, while IDD is a very nonspecific marker, it being elevated can sometimes point you in that direction. Those who have one autoimmune disease often have many autoimmune diseases. And so, the presence of other autoimmune conditions can lend some credence to this diagnosis. But, really, having a liver biopsy is key. And, from a patient perspective, the symptoms can be, can vary from zero symptoms to this kind of fatigue, lethargy, anorexia, kind of annoying right upper quadrant pain, and pruritus. So, in cases of acute kind of flares of autoimmune hepatitis, these are the typical lab findings you would see. So, the ASTLT being in the hundreds of thousands like this patient presented with. The OCVOS being relatively low to normal. And then, the total belly being high. And so, this is a classic autoimmune flare. So, these were the labs he had to start with. We got him on treatment. And, this was actually his labs as of last month. So, market improvement. Not total normalization just yet. He did not want to come to Indianapolis for further care. He lived about two hours north. And so, he's following with the local gastroenterologist in the area. Taking mycophenolate mofetil up to 1,000 milligrams twice a day now. As well as prednisone. And so, he's doing well. I did want to share. There's actual diagnostic criteria for autoimmune hepatitis. Most of us in practice probably don't go through and calculate this again. But, this patient did have autoantibodies that were, you know, positive. His IgG was markedly elevated. He had typical findings on liver histology. And, he didn't have any coexisting viral hepatitis. So, he had a score of eight. Which gives you this definitive diagnosis. And so, more comments kind of on the diagnostic criteria for autoimmune liver disease. You really cannot make the diagnosis without a liver biopsy. So, that's a really important point. Even if the autoimmune liver markers are sky high. To commit somebody to, you know, most people are on lifelong treatment. Immunosuppression for this. Without having that definitive biopsy. I do not do. And, like I mentioned earlier. 20% of patients who have autoimmune liver disease. Actually have none of the typical biomarkers positive. So, you don't want to miss those patients either. The other thing the biopsy gives us. Is it does help us to know how much scarring is in the liver now. As a result of, you know, many patients go years and years without the diagnosis just because they weren't having any symptoms. And then, especially nowadays, just to be able to rule out coexisting liver diseases, co-factors of liver disease, like metabolic-associated liver disease or other overlap syndromes with autoimmune diseases. All right, so on to our next case. This is David. He is a 56-year-old who has a history of bipolar disorder as well as hypothyroidism, secondary to Graves. He also has COPD, some coronary disease with a stent remotely, and he comes in with several falls at home and anorexia. And these are the labs that he comes to the ER with. And so, AST-ELT, mildly elevated. His ALK-FOS, pretty markedly elevated. Lily Rubin, somewhat high. And INR is also high. But he is not confused. He is completely with it. So, we get more lab tests. His TSH, one of the highest I've seen, upper liver normal being 4.2, and his 3T4 is low. He has an elevated antebrow BNP, a mild elevation in his troponin and the lactate. So, we get some imaging. And on this ultrasound, you see he has a normal appearance of his liver contour, right? Very normal. His gallbladder without significant stones or sludge. He does have trace ascites, and his liver is brighter than it should be. So, we get more tests. So, this is his cross-sectional imaging. So, you can see the perihepatic ascites here. But he has a relatively normal liver contour otherwise, but he does have trace perihepatic ascites. So, when I look at his x-ray, it's something I don't usually look at, but he does have cardiomegaly as well. So, that leads us to the echo. So, he has an ejection fraction of 20%. Global hypokinesis. He has some biatrial dilation, RV dilation. He's got severe mitral valve regurge, and he has an elevated RVSP of 40. No pericardial effusion. So, I'm gonna stop here and talk a little bit about heart failure and elevated liver tests. We get this consult all the time. So, typically, an acute heart failure episode or ischemic episode, you will see correlate with hepatocellular elevation of liver enzymes. So, marked elevation of the ASTLT. Sometimes in the thousands and thousands, and that's when you get the panic call. For chronic heart failure, you will typically see more of a cholestatic hepatocellular mixed picture. So, a little bit of elevation in the ASTLT, but mostly, it's the ALKFOS. And right heart failure, in particular, you will see elevations in the ALKFOS and the INR. So, if you see a marked elevation in ALKFOS, think that someone probably has pulmonary hypertension or just really high right-sided pressures. Albumin is typically low, but again, it's because it is an acute phase reactant. If they're presenting in the hospital, usually, they're acutely decompensating from the heart failure or ill. That doesn't necessarily correlate to underlying liver disease, but not to discount that people can have heart failure and cirrhosis, right? So, long-standing heart failure can predispose to things like cardiac cirrhosis, and especially in our patient population that's now coming of age, you know, 20, 30 years, post-Fontanne, you will often see, because of the changes in physiology, changes in the liver that can correlate with cirrhosis. And so, you can have cirrhosis and heart failure at the same time, but to kind of do a deeper dig and assessment of the liver enzymes and imaging to get a sense of what's going on. So, what makes liver tests better? Treating the heart failure. So, this patient, because of his thyroid testing being so abnormal, does get an endocrinology consult, and they actually think he probably has myxedema, and that's what's resulted in his falls. So, they recommend IV liver thyroxine. So, the question is, really severe hypothyroidism can put you at risk for heart failure. So, what came first? Was it that he just had heart failure or did his really uncontrolled thyroid disease for a long time cause weakening of his heart? I think that's likely what it was, but. So, I want to talk a little bit about the thyroid and elevations in liver chemistries, because we also get those consults all the time. So, extremes in thyroid function, so hypo or hyper, that's extreme, can cause elevation in liver tests. Typically, it's a hepatocellular pattern, but you can present mixed as well. Thyrotoxicosis or myxedema coma, those are the kinds of extremes that you'll see these chemistries being off in. Other things to consider, many of the drugs used to treat, especially hyperthyroidism, are actually implicated as drug-induced liver injury agents, so keeping that in mind. But the treatment is improved control of the thyroid disease will help over time resolve the liver chemistries as well. So, a little bit more about this patient. So, he was being diuresed once we found these findings, and liver tests were getting somewhat better, but then he spikes a fever. All of his blood culture bottles are positive for bacterial infection, and then we had signed off, but they call us back, because now his bilirubin is on the uptrend. So, what is going on now with this patient? So, this is a term that we use all the time, but just to kind of break it down a little bit. He has an active infection, and likely the bilirubin piece of this is because of cholestasis of septicaemia. So, this can be either from directly from the breakdown of bacterial products in the patient, or many times also it's the host response to the infection that can lead to jaundice. So, I was a biochemistry major back in the day, so I'm taking it back to basic physiology. So, bilirubin carried it through the bloodstream with a bound albumin as it enters the podocyte, gets rid of that albumin, becomes conjugated, and bilirubin by itself, very hydrophobic, right? So, it won't be easily secreted into the bile ducts unless it becomes conjugated. So, it gets conjugated and then goes across the membrane and out the liver. In septic states, you have an increased load secondary to hemolysis, some of that is an autoimmune hemolytic anemia that you'll see, and so you kind of overwhelm these transporters here. Many times patients will have ischemic hits to the liver because of the septic state, right? They're on pressers, and so those hepatocytes are shocked, and so the normal mechanism that should be working don't work as well. So, you're having less of this happen. There's oxidant stress that happens, there's DIC that happens, and that all leads to decreased bile flow, and that's why we get these elevations in bilirubin. Typically, when it's just sepsis alone, you'll see bilirubin elevations in the 2 to 10 range. We most times see this markedly higher, but that's usually because most of these patients have some degree of liver, other things that are causing liver injury. Many times, even some of the drugs used to treat sepsis can cause liver injury, and so you'll see it be higher than that most times. You may see a mild elevation in the transaminases, AST and ALT, and even ALFOS will go up. All right, so I wanted to share, and I'm stealing this from this reference here. Dr. Fontana, Bob, had written this great practice guideline for ASLD for drug-induced liver injury and how to kind of approach liver chemistries that are abnormal in that lens, but I actually really like it for, in general, how to approach elevations in liver chemistries. I have changed it a little, so if you go to the reference, you will see it a little different than what his is, but if I see two occasions of elevated liver chemistries, AST, ALT, ALFOS, then that makes me want to do more. If I see a total bilirubin that's greater than 2.5 with either an elevated AST, ALT, or ALFOS, an elevated INR with, again, one of the other liver chemistries being abnormal. So, the next step is take a very thorough history, if I can. I talk about homemade tattoos, homemade piercings, IV drug use, snorting drugs, or illicit or not illicit, blood transfusions before 1992, Ayurvedic treatments, homeopathic medications, herbal supplements, any family history of liver disease or autoimmune diseases, and then also getting a good thorough alcohol use history. I also like to discontinue unnecessary medications. Obviously, usually have co-signature from the PCP in those cases, but as long as none of them are, you know, very critical medications, trying to get rid of what I can. And then you see that you can kind of go through and do the R ratio to kind of classify it in hepatocellular mixed, which leads to a different role of diagnostic testing, or cholestatic, which leads me down a different path. So, this is a lot of testing, some of which we kind of went through in our cases here, but depending on what etiology I'm thinking and what kind of tests we do. So, we can see the thyrotoxicosis and hypothyroidism is on there. The genetic testing that we typically do, many times Bud Kiari, especially in my pregnant patients, we think about getting a Doppler ultrasound and then drugs and toxins. For cholestatic things, it tends to be more things like, you know, bone disease can cause market elevations in ALKFOS. Infiltrating cancers can cause abnormalities. TPN, cholestasis, you see a lot. And then, kind of putting it all together, if we do all of this other kind of evaluation modality, whether it's blood testing or imaging or endoscopy, and that's all negative and we can't find a culprit for the elevation of liver enzymes, that's typically when I'll consider a liver biopsy if either the presentation is really atypical or if I'm concerned for autoimmune hepatitis because I want to rule that out or in definitively if that's where things are looking like they're headed. I think that's it. So, questions, I'm happy to take. Hopefully, you all got at least a brief snapshot into a hepatologist's mind. On the first patient with the COT, the HEV IgM was positive and the RNA was pending, I guess. What, I was in the thought that that was the diagnosis. What led you to look for the COT toxicity? Yeah, that's a good question, especially because the liver tests were elevated in a way that would make you think it could be hepatitis E. Hepatitis E, and I have a whole lecture about this because I love talking about it, but hepatitis E is one of those viruses, you know, if you get hepatitis A, your body develops IgG against it. You should never get hepatitis A again. Hepatitis E is not like that. You get hepatitis E once, you may develop IgG for a temporary period of time, but it's not lasting. And so, you can reinfect yourself over and over again with hepatitis E. I think that hepatitis E, actually, in his case, given the presentation, could have been the diagnosis. And so, I think because he was inpatient and admitted for this and because it had been going on for a few months, everyone felt like we had to do something else next and we had to do something now. And so, I think that's what prompted the liver biopsy. Had we not done the liver biopsy, very well could have just said, hey, this is hepatitis E, because the RNA quant testing actually takes, it's a send out most times to ARUB, and it can take a week plus to come back. So, you're not, that's the other thing. You don't want to keep, right, you have the houseless breathing down your neck. Like, we don't want to discharge this patient. You don't want to keep the patient there for a week, waiting for that test to come back. So, I think that was also part of what, you know, tipped the scales in getting the biopsy, because most times, if I can get the biopsy before noon, I can get at least a prelim read that day by my pathologist. So, seeing the findings we saw on the biopsy, hepatitis E was out of, you know, out of the mix immediately, because of how that looked. So, it's a good question. Other questions? Any questions about approach, or? I'm guessing these are all diagnoses. You guys are consulted on and see, because many times GI is the, you know, the initial, you know, even at our sister hospitals where there are no hepatologists, GI is the one kind of heading off that initial workup and testing. Thank you for a great lecture. Can you hear me? So, for the first patient, did you treat that patient with corticosteroids? What was your approach in regards to, do you hear me? I'm sorry. Okay. It's not on, I think. The first patient, did you treat it with corticosteroids, and what is your treatment approach in regards to the corticosteroids in these drug-induced autoimmune hepatitis patients, and in regards to weaning them off corticosteroids? So, that's a great question. I didn't go into how you treat drug-induced autoimmune hepatitis when it's related to COT. There's no consensus on how to treat that. I, because of where I practice, and there were a lot of Yemenese patients there, I saw it not infrequently. Most times, we could actually get by with just telling them to abstain from the COT use, and over time the liver enzymes would return to normal much quicker than I would see in, like, say immune checkpoint inhibitor autoimmune hepatitis or things like that. But the major studies that have been done in kind of larger cohorts of patients that have had drug-induced COT liver injury have come out of Egypt and Saudi Arabia, and really have not been, they've been kind of all retrospective reviews, and so it's a mixed picture. Sometimes people will start steroids for a short period of time, like we do with these other drug-induced autoimmune hepatitis. Many times people will do nothing and just see how they do with time away from the substance. There's no consensus. I personally, if someone was very symptomatic like he was, I actually do give steroids, and so start with 60 inpatient, go down to 40 outpatient, and typically taper by five every two weeks until I see improvement clinically in the symptoms, and usually that follows with the lab testing. If patients are not very symptomatic, because I've had multiple patients just come to clinic with this, right, they're outpatient, they're thriving, they're going about their lives, they're just liver enzymes, they're abnormal, those patients are the ones I will talk about abstinence and withdraw from that drug, and typically those will resolve in time, and they're not symptomatic. But if they're symptomatic, I do typically treat. There's nothing in any guideline anywhere to tell you what to do, because it's not described very much, except for in certain countries, but we definitely see it here in the U.S. I know my patients grow out here in the U.S., so it's just, you have to think about it, so. Other questions? Yes, so IV NAC, that's actually a great question. I think I go off on tangents with this with my fellows. So I actually think when I get a patient who comes in with acute liver injury, and they're inpatient, you know, their liver enzymes are significant enough or their symptoms are significant enough to warrant an inpatient admission, I typically, unless the patient has an allergy that's known to N-acetylcysteine, I will start it. That, and depending on what the pattern of liver enzymes are, if the bilirubin is really low, if the AST, ALT are really high, I will also empirically start acyclovir typically as well, just if the clinical picture fits that it could be an HSV hepatitis until that HSV PCR comes back. But the NAC, you know, regardless of the liver chemistry elevation pattern, I typically will start until I can get a better idea of what's causing what. There's really no downside unless a patient is allergic to one of the components. But there have been studies to show that it does help just from an antioxidant perspective with inflammation of the liver. And so if there's a chance. Hi, great, great presentation. What would you say, though, would be your most cost-effective approach? So you get the consult, day one, what tests are you telling them? Order these tests because, you know, it's the hospitalists, they want to get them in, get them out. What's your short list? I think, so that's where going back to Dr. Fontana's kind of diagnostic algorithm, right, I do this day in, day out. This is, you know, my brain is wired to think about what are the most likely culprits when I see certain test pattern elevation. I actually get on my fellows about doing the kitchen sink approach, right. And like you don't need to send every single thing. You need to send the things that are based on the kind of elevation you see. So I think, you know, having, sorry I'm trying to get to this last slide, trying to have a rubric or an algorithm like the one you see, depending on what pattern of elevation you're seeing and kind of correlating with the clinical history, that's the kind of approach I take when I go to doing that workup. And so I know that's not a, it's not a simple kind of approach per se, but I really do follow this for the most part. Like I agreed that I didn't modify a whole lot of what Dr. Fontana put on here, but depending on what category of elevation, liver test elevation they have, it's kind of what I do. So many times people are like, well why aren't you ordering an MRCP, you know, for someone with elevated belly ribbon? I'm like, well if it doesn't clinically fit and if there's no other indication for it and then they really do fall under something else in this section, then I'm not going to order an MRCP and wait three days for the MR scanner to be open for that patient. Like, you know, I feel confident enough without it. But I think that's, you know, some of the viral testing, the acute viral testing, most of it will come back quickly. With hepatitis E IgM, unfortunately, most places don't have a reflux. We don't do RNA quant testing. And so the hep E IgM comes back quickly, but the RNA test can take forever. So just having a high clinical suspicion, but hepatitis E IgM is often falsely positive too. So that makes that hard. It's hard. That's a hard question. Because like you said, there's a big push to get these patients in and get these patients out. But a lot of our tests don't come back quickly. You know, all these autoimmune markers take days to come back. And so, but I think using something like this rubric to try to help guide your diagnostic testing is helpful. Sorry, sort of a tangential question. Cardiac cirrhosis, do you do hepatoma screening for those patients? Yes, I do. So I, my practice, I focus on pregnancy and liver disease. And so I actually have a lot of reproductive-aged Fontan female patients, post-Fontan physiology. And so, one, when they come to me from the, you know, peds cardiologists, they try to determine staging of fibrosis. And if they definitely have either by FibroScan, by biopsy, by imaging evidence of cardiac-related cirrhosis, we start screening. And that patient population kind of also tended to, even without full-on cirrhosis, they are at a higher risk of HCC development. So it is very important. So I do, once you've made that diagnosis that they definitely have fibrosis, you should start HCC screening. Other questions? Really good questions. I hope you guys are enjoying the course and the symposium so far. If any questions, feel free to email me. I can try to send that back, put that back up. Or find me on social media. On Blue Sky, you're just going to see a lot of politics. But on Twitter, I typically will have more academic backings. Thank you.

transplant hepatologist

gastroenterologist

liver injury

acute liver failure

diagnostic criteria

R ratio

liver biopsy

clinical decision-making