Is FIB-4 calculation an okay stand-in for elastography? It isn't done at my local hospital, so I have to send my patients two hours away with a $28 toll, plus most are hourly workers without time off benefits, so they'll miss a day of work and run the risk of being fired. I think, Dr. Martin, did you want to address this one? I'm actually going to ask Andrea if she can, because I'm not familiar with FIB-4, and that's something I'm going to learn from her. Well, yeah, so thank you for the question. FIB-4 is a calculation, as this person who's asking the question likely knows, in order to determine the sort of prognosis, the stage of fibrosis. It is a calculation that can be done without fancy imaging, and thankfully, therefore, the utility is great. I will be very frank in that where I practice, we do rely heavily on our fiber scans and MR elastography, so I use it less than many of my colleagues, but that I do believe is a good substitute for a fiber scan. Andrea, can I ask you something really quickly here? I take it you perform fibro-scan exams yourself, is that right? That's correct, yeah. Is that something that is commonly done by APPs? Is it difficult to learn, easy to learn? What's your take? So there are a number of non-invasive assessments for fibrosis, including shear wave elastography that are performed by our colleagues in radiology. The fiber scan is nice because, again, the machine is relatively small, it's portable, and we can roll it to do point of care. The training through the company is about a four-hour training, and then with an assessment of competency, and then one could argue, one of my colleagues, Dr. Patrick Hammond, said there's actually a study that suggested you're most competent if you performed 100 of these, so I've clearly gone beyond 100 by now, but the skill set, really, it's relatively easy to learn. There are practices that have the nursing staff doing them as well, and some of my physician colleagues will perform them during the clinical evaluation, so very user-friendly, yeah. Great to know. Next question is, when do you order a liver biopsy, and in what situation? I can take that. I'm going to assume this person is asking in the setting of cholestatic disease, because I do think that the rules, if you will, are different, depending on what the underlying liver disease is. In general, for cholestatic disease, it would be uncommon to order a liver biopsy, again, unless you had a patient who you were highly suspicious for primary biliary cholangitis, and yet the anti-mitochondrial antibody was negative. In those settings, a biopsy may be helpful to confirm AMA-negative PBC, and again, because we have good therapy options, it may make sense to perform a biopsy. I think performing a liver biopsy in the setting of primary sclerosing cholangitis would be rare. My only caveat to that would be that the patient has underlying inflammatory bowel disease, they have a cholestatic profile, and the MR cholangiogram shows you nothing. There are perhaps 15% of all patients with primary sclerosing cholangitis where it's what we call small duct, meaning you can't see it on an MR cholangiogram, or if I had Dr. Martin do their ERCP, he wouldn't be able to see it, because there's really no involvement of the large ducts. That may be a situation where you want to perform a liver biopsy, but beyond that, usually in PSC, it's not necessary. Autoimmune hepatitis, however, I would say that you should consider a liver biopsy to confirm the diagnosis. Andrea, do you sometimes order a liver biopsy these days in the last setting there to document response to treatment, et cetera? Yeah, so that's an excellent point. Once you have a patient on therapy, and certainly if you're considering withdrawal of therapy, there's good evidence to suggest you perform a liver biopsy to confirm that the disease is inactive before you fully withdraw therapy. Thank you. Our next question, this person says, I feel like I struggle to not order the million-dollar workup when patients present with abnormal liver tests. I tend to lean on ordering AMA if ALKFOS elevated, AFP if cirrhosis, but otherwise, I am ordering the whole shebang. Do you have any guidance on how to better unpack the patient presentation with elevated AST slash ALT? Well, I think if it's an elevated AST and ALT and there's not really evidence of a cholestatic liver disease or if it's mild elevation, then I think you need to think through what are the other potential causes. Drug-induced liver injury or DILI, Dr. Martin alluded to, we see that not uncommonly. I have a gentleman right now who's on seven different herbal supplements and we're seeing elevations of his liver test because of that. I do think you can be very thoughtful as you work through the diagnostic algorithms to make sure you're coming up with a probable cause without doing the quote-unquote million-dollar workup. I think in the event you're moving through and you've come to the conclusion that it's some sort of cholestatic process, it's difficult. You could consider an abdominal ultrasound and ultrasounds are good at picking up upstream dilation from a presumed downstream stricture. It's just ultrasound, it's going to be more difficult to really confirm that there's a ... It would be a challenge to really be able to see true PSC or biliary tract disease. It would have to be pretty significant before it's going to be evident on the ultrasound. But to the question, I think you work through things gradually. I agree, we don't want to order a bunch of tests up front. We need to move through that methodically to make sure that you're not able to arrive at your conclusion or diagnosis sooner, only moving to the more expensive tests if need be. I don't know. John, do you have any thoughts on that? That's a great explanation, Andrea, because it's hard to provide a single one-stop prescriptive answer because the question is really broad. It's a very situationally nuanced answer that we have to give you because some of it has to do with not just even the medical or clinical aspects of the patient, but what the social or even geographic issue is. If this is a patient that comes to see Andrea from the West Coast or something, and you're not going to be able to see them again for months, then you may have to order more stuff than you might for someone who lives three miles away just because of the patient's access. Or even insurance issues may have something to do with how much or what you're able to order at any given point in time. Some of it is driven by patient acuity of presentation or whether you think that there's a possibility that some of that workup may have been done elsewhere, and you might be able to access those results by contacting someone even though they're not available on your EHR because you're not on the same network. I think the answer has to be adequately nuanced, and that's the only thing that I wanted to throw in on top of your erudite answer to the question. So our next question is, are there hereditary or environmental risk factors per primary biliary cholangitis? This person has diagnosed this three times in the past two years with a service population of around 46,000 patients or people. They feel this seems high, and these patients were not related, and they don't live in the same area. So any thoughts on that? So we certainly do see that there are pockets geographically that there seems to be an unusual number of patients that may be related to sort of that Northern European ancestry and the increased risk for PBC in those patients. But in general, to the point of sort of environmental triggers, we don't yet know what those may be. There's a lot of work being done in this space by Dr. Costas Lazaridis, one of my colleagues at Mayo Clinic, and I do think one day we will be able to be more specific about that. But at this time, I would say it could just be by chance. There might be that component of sort of, you know, sort of their background, but I also think that there is just a greater awareness for making the diagnosis today than there probably was even a decade or two ago. The approval of E. coli, I do think, raised awareness for some, which has been a terrific thing, because people are getting on treatment earlier, and that really is the key, is getting them on therapy as soon as they are diagnosed. But as with any autoimmune conditions, you can sometimes just see these kinds of pockets where you see more cases than perhaps in other areas. Hard to know exactly why. John, I don't know if you have other comments on that. I don't have anything to add to that, Andrea. That's interesting and educating to me, too. Andrea, there is a fibro lab test you can mail out, this person says, as well, if the fibro scan isn't available. What are your thoughts on the lab test compared to the scan? So I have to say I'm not actually familiar with that. Are any of the other GI hepatology folks on the call familiar? I don't know what that is. Sarah, have you heard of that? Is that the fibro lab test? Sarah, have you heard of that? Is that the FibroSure, maybe? Boy, I don't know. We've used FibroSure in the past, the blood test for it, which is a send-out lab. We've largely replaced that with FibroScan. The comparison is actually quite good, and we had done a literature review prior to getting the FibroScan. But we find that the ease of the FibroScan, just having it in the office and being able to perform it and have that real-time assessment has been really helpful for us. We primarily were using it for patients who had hepatitis C and needed to have a fibrosis score prior to having treatment. And so we rarely use it now. I would say in the last two years, I maybe ordered it once. And I can remember a patient who lived about four hours away. I had done a video visit. So rather than have them come in to do a FibroScan, I had ordered the blood test. So it works well, but I think that it's not needed if you have a FibroScan available. Yeah, I just want to add from a broad overview for the audience, there have been many attempts to study liver fibrosis. And liver biopsy remains the gold standard, so to speak, but is invasive, can be done in multiple ways. Number two is the non-invasive imaging, which is FibroScan nowadays in our clinics, but also MR elastography, shear wave elastography with ultrasound and so forth. There are a lot of attempts at doing non-invasive imaging on that. Finally, there are blood tests, which are the so-called non-invasive markers of fibrosis. They have been studied for the last quarter century and FibroSure is one such commercially available test. So the number of times it's done is relatively inconsistent as Sarah just said, but these are out there and you just have to weigh in the yield of doing the test versus the cost and how much you can rely on that. And our next question is, can you explain why gamma globulin needs to be checked if there's a concern about autoimmune hepatitis? Can the immunoglobulin G levels be checked instead? So we use IgG4 to look for autoimmune pancreatitis or autoimmune biliary tract disease. We don't use that to confirm the diagnosis of autoimmune hepatitis, that we use the gamma globulin. I don't know if others have thoughts on that. Yeah, I think what I want to say to that is that the total immunoglobulin test, not the subtypes, but the total immunoglobulin testing is done and we do it, and it frequently is elevated in the common variety of autoimmune hepatitis. And I think it adds another data point to your diagnostic criteria. And of course, if you're looking at specific subtypes, then that's what you're going for. For the previous question, I failed to add that these non-invasive tests are usually best performing in the extremes of the fibrosis. So no fibrosis and cirrhosis are relatively easy for them. Stages two and three are more difficult. And that's true for all modalities in my mind, but Andrea and John can correct me if I'm wrong. No, completely agree. Okay, we have an open, or we have a raised hand, excuse me. So, Sarah Stanko, we have unmuted you and you are welcome to talk. I think you might have your cell phone on, so you just need to unmute yourself. There you go. Can you guys hear me? We can. Thank you. Go ahead. I was going back and forth. We have done the rectal variceal, the glue injections on our patients. And I think you guys already answered my question. So sorry, my hand was raised. But as far as the APP role, I know that we've had some patients that have really low platelets and we've done an extensive blood workup on those patients. And I can't think of what it is, but just their further coag times. I didn't know if you guys do that in your practice or just order blood products before the procedure. I'm going to ask you to rephrase that question, Sarah. Can you ask the question? Yeah. For the patients that need like the glue injections, do you guys pre-order blood products before the procedure on, I guess, an outpatient basis or inpatient basis? I don't see patients on the inpatient side. So I guess, do you do all this workup prior to the procedure? Well, I mean, a couple of things, Sarah. First is that glue injection, I'm assuming you're talking about glue injection of varices, usually done for gastric varices in the United States, rarely elsewhere because band ligation works in the esophagus. Yeah. Gastric varices. But we've also done rectal variceal advanced procedures where I'm at. Yep. You can do that. Blood, in other words, blood products for infusion, for supplementation, the ordering of that for a patient who's acutely bleeding is the same regardless of what endoscopic modality you're entertaining using. So I'm assuming the clinical situation is an acute upper GI bleed due to portal hypertension, specifically due to gastric variceal bleeding. And in that case, in admission to the ICU, usually frequently with endotracheal intubation and giving loads of crystalloid to get the blood pressure tanked up. And also at the same time, typing and crossing for blood product infusion, all of that is appropriate. And whether you're ultimately going to use band ligation, which would be temporary in that setting, the placement of a Minnesota tube, for example, to staunch bleeding or even the use of glue really wouldn't influence the ordering of blood product. It's the clinical situation of the acute portal hypertensive upper GI bleeding that indicates typing and crossing for blood products. Does that make sense? Yes. Yes. Thank you. Just wanted to make sure that that's clear. Thank you so much, Sarah. And thank you, Dr. Martin, for that dialogue. We have a request here. Someone didn't quite catch the recommendation regarding surveillance imaging for PSG. So in general, what we do is an annual MR cholangiogram with CA19-9. We used to use ultrasound, but once we switched to MRCP, we really had a hard time going back. I would say that we'll add in ultrasound on the off six months if patients have evidence of cirrhosis, just for HCC surveillance. So CA19-9 plus an MR cholangiogram on an annual basis, if possible. And we have a request to go over varicea screening in patients with cirrhosis. So from an outpatient perspective, I will say that the patients that I'll send for an upper GI endoscopy for variceal screening would be those that have evidence of advanced fibrosis slash cirrhosis on imaging or fiber scan. And particularly if the platelet level is low or they're splenomegaly on exam or on the imaging study, those would be the candidates that I would send for an EGD. So this person asks, can you please elaborate on the effectiveness of fiber scan after hep C treatment? Well, that's a great question. I actually haven't seen any data whether or not, I mean, presumably if they're relatively early stage, there may be some improvements in fibrosis, but I really don't manage C patients often. So I don't know if others have comments on that. You know, this has been addressed in the way in the past when we were early on in our liver disease management journey back in the nineties and so forth. The big question used to be, does cirrhosis ever regress? And there were some case reports where they were able to demonstrate said regression. Now, the counterpoint for that was that fibrosis can be very patchy as Dr. Schiff had shown two laparoscopic biopsies from each lobe a long time ago. So I think the jury is still out in general. In general, the well agreed upon fact or factoid is that once you treat a treatable underlying chronic disease, liver disease, you do halt the progression of fibrosis from that point on, just like you reduce the risk for lung cancer the day you stop smoking, provided other risk factors are not coming along as well. So if you treat hep C, so you're doing good from a hep C fibrosis standpoint, but then if you start drinking alcohol or get NASH, you know, you'll continue on your journey with liver disease. So that's how I would answer that. Our next question is, what are short and long-term tips for, let's see, they say complication. Can you elaborate on beta blockers in the setting of esophageal varices? Sure. Tips. Thank you. It sounds like you understand the question. Yeah. Unless the tips they're referring to is the procedure, the tips, if it's tips as in tips regarding management of a non-selective beta blockers, I would simply say that in the event, again, we talked about when you would order that screening endoscopy. Once you've done that at our center, they're rated as small or large with the threshold being five millimeters. I don't know if that's universal, but that's the criteria we use. And so if they're small, we would use primary prophylaxis at that point. So I would start them on low dose beta blockers with a goal of blood pressure around 100 over 60 and pulse 55 to 60. We'll have to sometimes titrate their doses as needed. Now, in the event they have large varices, particularly with high risk stigmata, then I hopefully have had a conversation with them up front because sometimes if the endoscopy is being performed, they're going to need to start banding right then and there. So I always try to have that conversation before I even send them for the procedure so that they are aware of the potential outcome. But in general, primary prophylaxis if small varices and no evidence of prior bleeding or high risk stigmata. And Andrea, what changes, if any, if there's intolerance to the pharmacotherapy that you've attempted to initiate? Yeah, that's a great question. And we definitely have patients where the fatigue is so profound or we simply can't get them adequately treated to feel good about their primary prophylaxis. And I have had patients who have said, I want to go ahead with serial banding simply to get off of the beta blocker. So that is a conversation that we have. And I was just going to say that, sorry, go ahead, Joe. Go ahead, Vivek, just in case we say the same thing. Yeah, for the liver disease patient, you know, three things. The beta blocker question is extremely important for primary prophylaxis, also for secondary as well. But that's a quality metric really. I mean, it's, you know, along with vaccination for liver disease patients and hepatoma screening, if these are the three things you're doing for these patients, you're checking most of the boxes. But if a patient with established cirrhosis and, you know, portal hypertension is found not to be on beta blockers, bleeds and has a negative outcome, and, you know, they've been under your care for a while, that's not going to be an easy one to defend. I just want to add that when Andrea brought up a good point when she talked about the stigmata, perhaps, or high-risk findings of bleeding, in addition to size, we look for these spots. They're affectionately known as red whale spots, but they're actually just these slightly raised red spots on the varix that could be a sign of recent bleeding or, again, a risk factor for bleeding. So just to make sure when everyone understood that when she said stigmata or risk factor, just that's something you may see in a report or hear your collaborating endoscopist discuss. I think it's also important just to make sure these patients are educated on the risk in the event that they have evidence of an acute bleed. This is an emergent, which hopefully everyone would recognize, but I always have the conversation. If you ever begin vomiting blood, have melanin stools, this is something we want to know about right away. It's got a high mortality rate. I believe it's around 20%. I'm sure someone may know that more accurately than me, but it's something where we really just need them to be aware of any signs or symptoms and prompt evaluation in the event they develop them.

liver disease

FIB-4 calculation

elastography

liver biopsy

abnormal liver tests

variceal screening