Thank you very much, Dr. Martin. That was fantastic. I think I'm going to start the Q&A with you if you don't mind. There was a question about the elevation of isolated bilirubin and normal transaminases and kind of your thought process on how to work that up. Yep. So remember that bilirubin can be fractionated. So oftentimes what happens when a bilirubin is elevated is you'll see two things. You'll see the bilirubin fractionated, so you'll see a total and direct. And then you will also see that other liver tests, typically the liver enzymes, the aminotransferases AST and ALT, as well as an alkaline phosphatase will also have been ordered. Now you're suggesting that the AST, the ALT, and the alkphos are all stone cold normal. If they are all stone cold normal, that right there makes the likelihood that the bilirubin elevation coming from the liver or the bile duct is less likely. Then going to go back and look at the total versus the direct fraction. If the source of the bilirubin elevation is liver or bile duct, you're going to see an elevation in the direct fraction of the bilirubin, the direct bilirubin. I would bet you that in the majority of cases that you encounter in your career, if the AST, the ALT, and the alkphos are stone cold normal, and the total bilirubin is elevated, it's going to be indirect hyperbilirubinemia where the direct is probably going to be normal or pretty near to it. And the bilirubin elevation is going to be due to something other than the liver or the bile duct, such as excess hemolysis for whatever reason. Or the patient may have a syndrome like Jill Bear syndrome. Thank you so much. Eric, I know you answered a lot of the questions about the management of IBD in the Q&A. And so I'll refer everybody to that. And if there's some additional questions, just send them to the Q&A now. But I did want to highlight the question about vaccines, because I think that's a really important one. Can you talk about what vaccines are safe in patients who are on therapy for IBD? Yes, yes. And I definitely should have mentioned this in the talk. So when a patient is on a biologic, they cannot receive any live vaccines. So non-live is fine. In the Q&A, someone wondered if their patient, you know, you do your hep B screening before you start a biologic and say that they are not immune, they can definitely get the hep series while on a biologic. But you cannot receive live vaccines such as MMR or our previous herpes zoster vaccine that was live. You cannot receive live vaccines when you're on a biologic. And then I think just coming off of that, what was the recommendation regarding COVID and the COVID vaccines? Yes. So our recommendation is to get the COVID vaccines as well as the boosters. We have great data that our IBD patients develop a robust antibody response to COVID vaccines. The only hindrance to that antibody response is high dose steroid use. So in our patients who are on high dose steroids, we recommend that if we can start tapering below 20 milligrams, that's the best time to give them any vaccine so they can actually mount a response. Thank you so much. There's a question about acute pancreatitis and how long to continue the aggressive IV fluid resuscitation. And so in general, that's 24 to 48 hours, and it really should be goal directed, meaning that you're frequently assessing their hemoglobin and hematocrit, and you're actually looking to see that you're starting to get that dilutional effect. You do have to be cautious in patients who have CHF or chronic kidney disease and have chronic kidney disease and watch for fluid overload as well. So there's a bit of a balance there, but really looking at the hemodynamics, the hematocrit and the BUN and directing it based on that. Eden, do we have some other questions? We sure do. What do you do when the ALKFOS is high, but the ALKFOS isoenzyme is normal? Yeah. So let me first clarify what's meant by isoenzyme. So when I was talking about fractionating, you know, bone versus liver ALKFOS, the isoenzyme thing means the same thing. You know, much as my talk reflected, medical terminology is really unfortunate. You know, there's 8,000 different ways to say the same thing, and they're most of them are a mouthful. It's just a horrible lexicon. But anyway, we're talking about the same thing here. So you're suggesting that the ALKFOS is elevated. Make sure I understand this question right. The ALKFOS is elevated, but the liver ALKFOS is normal? I believe that. I believe that's what that was the scenario. Yeah. Yeah. So then that suggests that the alkaline phosphatase elevation is not coming from the liver, but it's coming from another organ. So it's not coming from the liver or the bile duct. So, you know, it could be coming from some bone disease or metastatic disease to the bone or some myelophysic disorder, you know, some bone marrow disorder that's affecting the bone. I'm trying to remember where else ALKFOS comes from. It comes from the placenta, you know, so basically it boils down to a more generalized internal medicine workup at that point. If you want to, you know, quickly sort of assure yourself that it's not coming from the liver, you could check a GGT or a five prime. If that's elevated, then you're in trouble. You better check that ALKFOS again, make sure that it's not a lab error. And our next question is given the low incidence of alpha-1 antitrypsin death, do we only alpha-1 antitrypsin if known AAT death and pulmonary symptoms? I want to see that question. So knowing that alpha-1 antitrypsin deficiency is not common, then what's the rest of it? Question is whether we should always check it or only check it if there either is a known family history or known pulmonary symptoms that would give you a higher suspicion for alpha-1 antitrypsin deficiency. Yeah. So that's a really good question. And that depends on your practice. Okay. So if you are a referral hepatology practice, you're going to be much more likely to order a full battery of liver tests, which is a pretty expensive proposition. Why is that done? Because that's usually a destination patient who's already seen one or two gastroenterology practices already, and is being referred and have flown halfway across the country to see you. And you may not have a second chance or a third chance to draw specialty blood work. So you better get the whole battery right now. But if you're just starting a liver workup, my personal opinion is that it's not cost efficient to order the rarer tests. Get a good history, get a good physical, let that help you decide whether you're going to order which common tests first. Usually the common tests are common viral serologies, simple autoimmune markers, and an ultrasound of the liver and right upper quadrant with or without Doppler's. Those are pretty cheap tests that can be done just about anywhere. If and then the rest of the more specific stuff like alpha one should then depend on what the history, physical and those simple tests that you started out with make it more likely to yield. Does that make sense? Yeah, thank you. Yeah. I was going to actually shoot a question to you. There was a question about the use of MRCP and acute pancreatitis. And so if a patient has normal liver enzymes, but their workup is negative, and we're kind of going on the idiopathic acute pancreatitis, would MRCP be helpful in that setting of normal LFTs? So, yes, I think we do find our way towards an MRCP in many patients with pancreatitis for one reason or another. To specifically address the value of MRCP in a patient with pancreatitis, coming in with so-called idiopathic etiology. Remember that only a very small minority, probably a single digit percentage, truly warrant the moniker idiopathic. If you dig deep, you know, the usual statistical causes such as biliary and or alcohol or medications usually will surface as the cause. But MRCP helps specifically with the anatomical construct of pancreas divisum, as you correctly pointed out in your talk. Although endoscopic ultrasound is also quite sensitive and specific for picking up pancreas divisum, the patient may not have had an EUS, may not have EUS available easily locally, or high expertise EUS available locally. So MR does serve that purpose, because a 3D deconstruction, or even without that, a competent radiologist should be able to tell you that the patient has pancreas divisum. Now, here's a caveat that if the patient has pancreas divisum doesn't mean that that was the cause of their pancreatitis. That's also an important thing to take home, because 5% of the world's population has pancreas divisum. If it was a very common cause of pancreatitis, I would probably never go home and John would never go home. So that's how many patients we would have. So I think even in patients with pancreas divisum, it's important to consider the more common causes of pancreatitis, such as microlithiasis, biliary sludge, stone disease, and or medications. The other thing that the MRCP will tell us is the presence or absence of common bile duct stone. And sometimes, these are not picked up on CAT scans or ultrasounds, typically, so an MR will be able to tell you that. And then finally, in a specific subset of population, older patients, patients we know as high risk individuals for a variety of reasons, genetic composition, family history, but mostly in older patients who present with idiopathic pancreatitis, high quality cross-sectional imaging, such as an MR may pick up a cancer. Every so often, you'll have a tumor in the pancreatic head that has not been picked up on a study two or three months ago. So there's significant value there. But I think the protocols have to be done properly, the contrast injections timing and everything has to be done well. And the person reading it should be an experienced individual. John, I think you have some comments. Yeah, thanks, Vivek. I wanted to add to what you and Sarah are mentioning about imaging. And frankly, not only for pancreas, but also for bile duct. Unfortunately, both ultrasound and MR, including MRCP, are highly operator dependent. And the quality of imaging and interpretation of those studies is extremely variable institution to institution. So you know, a study done somewhere else in a study done at your institution may yield very, very different results. Thankfully, those are non-invasive tests. So they are largely without risk to the patient, although not without risk to their wallet, particularly MR. But sometimes repeating those can be worthwhile. If the study was not done well, because experienced operators did not perform or read the imaging study. Yes, I agree. I think going back to that question on the liver and liver testing, I think my general rule of thumb is exactly like we just said, right viral hepatitis and autoimmune markers on the top. Then if we start going metabolic, then I would go to iron profile as hemochromatosis being the more common one next up and then celluloplasmin for Wilson's disease. And then finally, things like alpha one and such, because that is, in my sense, the order of opportunity there and almost rarely do alpha one on a routine basis. So that's important. I do think that, you know, Vivek, you and I have sort of spent our careers at academic centers where a lot of the liver patients or, you know, liver abnormality patients or test abnormality patients are destination patients. And so we've had a probably in our career have mostly been ordering batteries of tests. But I realized that that's not the way to approach it. Certainly not in the community setting and in the early phases of the evaluation. I think it's just an uncommon event. But if you don't test, you will not pick up the uncommon events either. So the reverse is true as well. There was a question about autoimmune requiring liver biopsy. It's an it's an important question. I think, you know, if you are a purist and a traditional operator in this realm, the liver biopsy really is an important part of the autoimmune diagnosis. You know, clinching, there are features in the liver biopsy that contribute to a scoring system that is part of the initial diagnosis. Is it absolutely necessary? I don't think so. But I think, again, the book does say that liver biopsy is is required as one of the contributing elements. But more importantly, down the road for treatment monitoring and for prognostication, liver biopsy becomes very important because a certain percentage of patients, even though the disease course is indolent, they will progress to a more significant fibrosis and a small percentage will end up having liver transplant despite the best efforts. So although patients with PBC and autoimmune will remarkably do very well with transplant, these are some of the best patients that a transplant center wants to have because they do so well post-transplant compared to some of the other etiologies of liver disease.

liver function tests

bilirubin levels

indirect hyperbilirubinemia

IBD vaccines

acute pancreatitis