Good afternoon, everyone. I'm really excited about today's webinar. It's a timely and important topic that perhaps doesn't get enough attention. Today we have two fantastic speakers. Dr. Reem Shara is an Associate Professor of Medicine at the Weill Medical College of Cornell University. She's the Director of Interventional and Therapeutic Endoscopy, as well as the Director of Bariatric and Metabolic Endoscopy. Her research is primarily focused on interventional endoscopy. Our second speaker is Dr. Zach Henry. He's a Transplant Hepatologist at the University of Virginia in Charlottesville, Virginia. His work focuses on portal hypertension, specifically the management of gastric and ectopic viruses, and quality improvement in the management of patients with cirrhosis. Both are master clinicians and exciting speakers and communicators. Both have published extensively, demonstrated citizenship, and shown superb skills as mentors. However, both are considered wonderful people who are deeply collegial and care about everyone they encounter. This, for me, is perhaps one of the most important things we could say about those we surround ourselves with. I also want to thank the SLD for putting on this webinar, thank all of you for attending, and sit back and enjoy the show. We start with Dr. Henry. So Dr. Shariah is just going to share her slides, and I'm going to introduce a quick case and then let her take it away. And so we wanted to frame this around a case to try to give some real world feel to this as we talk about these very new technologies, so that you can kind of have a better understanding of when and where they may fit in your practice. So this case is a 55-year-old woman who has multiple metabolic risk factors, also had a history of breast cancer that had been diagnosed two years prior to referral, and was presenting with recurrent melanoma and mild anemia. Her outside provider had noted a first bleeding event four months prior to her clinic appointment with me. She had an EGD initially that really only suggested PHG per the reports. And then a few weeks before our appointment, she had a second bleeding event, again, just with melanoma and mild anemia, and this time suggested a possible gastric varicose, and so she was referred to me for evaluation. You know, imaging at that time suggested a normal-sized liver with some mild steatosis and possibly a mildly nodular contour. Her exam was negative for any overt signs of cirrhosis, no pulmonary erythema or spider angiomata. You can see her labs there on the right are pretty normal. Her platelet count is a little borderline. And then at this point, you know, we always have to ask ourselves, what do I need? You know, endoscopy, biopsy, do I need a pressure gradient? Do I need elastography or something else? And so this is where we start with our patient and then go from there. Okay. So thanks again for inviting me to speak and thanks again for the wonderful introduction. So hopefully by the end of this talk, you'll sort of agree with us that EUS and liver disease sort of go hand in hand and that you could use EUS for a variety of things or endoscopy. So measuring liver stiffness for PPG measurement to do a biopsy for variceal screening and banding and we're not limited by obesity or ascites. It's definitely a big topic. And if you can see the rise in PubMed publications over the last few years, especially sort of in the last three or four years. And this is sort of a slide I got from Ken Chang where he was sort of convincing us that we really should start looking at the liver. And initially we were ignoring it. And this is an easy way of just when you're doing an endoscopy and an endoscopic ultrasound to do what we call a sort of a pillow sign, just measuring the liver stiffness. So if it's more than five centimeters, then the liver is pliable. And if it's less than that, then you can consider that there might be some underlying issues. So the real obviously thing is to do elastography. So this is sort of fairly more recent. Liver stiffness measurement has become obviously an accepted and widespread measurement as a non-invasive test for liver fibrosis. And it was first introduced in the U.S. in 2013. In via EUS, you can do it in two different ways. One is by using a strain elastography and the other one, which is a newer technique, which is a shear wave elastography. So strain elastography measures the relative stiffness and you get a color histogram. It's not very accurate, but you know, you push hard on the scope, you'll get a hard measurement. You're soft, you get a different type of measurement. But this is a little bit better. It provides a KPA. We're still new on this. It's been available since 2019. But we're sort of not 100% sure on the measurements as you are with the fiber scans that you can get, but you can get sort of 10 measurements as I'll show you in a little bit. So this is shear wave elastography on 28 patients with cirrhosis and the overall accuracy is about 96%. And sort of you get, if you get 10.7 KPA or 14.0 KPA in the left lobe, that sort of more likely indicates liver fibrosis. And that has been shown in multiple studies. Last year at DDW or earlier this year, this is a study from Marvin Rue, basically showing that shear wave elastography is sort of more consistently, it gives you better consistent measurements, and it's more correlated with liver biopsy and your final biopsy, which is sort of the gold standard in patients with obesity. And that makes sense. With patients with obesity, you're sort of really pushing hard to get any measurements. So this is the fibrosis stage, and the KPA that you're getting with the shear wave elastography. And you can see sort of it highly correlates with that. And then doing the same sensitivity analysis to the different non-invasive measurements like the FIP4, the APRI score, the NFS score. And again, you see really good correlation. So it's still very early data with elastography. But hopefully, it's going to be a big player. What about US guided liver biopsy? So I know Dr. Henry is going to talk about this in a little bit. But basically, the advantages of doing US guided liver biopsies is that you can screen for varices and do the liver biopsy at the same time. You can do a targeted approach. So here you can see some masses, and you're able to biopsy them. Now, obviously, I'm speaking to a group of hepatologists, and I'm not a hepatologist. You all know the practice guidelines from the ASLD of getting at least two to three centimeters with at least a minimum of 11 complete portal triads. But we've tried multiple times to get good data for this. And if you look at our data with EUS over time, initially, it was reported back in 2015. And there's been variability in technique. I would say probably in the last two years, we're getting much, much better at doing liver biopsy. So here is sort of the grandfather who's really taught us how to do all these liver biopsies. Can shine showing a different approach using sort of a wet suction stylet technique, and what he calls a samurai approach of literally just jabbing the liver. You can see you get big cores of tissue with this. At Cornell, we've adopted this technique, and we're getting good measurements, and I can show you the data as well in a little bit. This is a study that was published a few years ago, basically looking at 152 procedures comparing EUS versus the transjugular approach. And what you can see is that roughly, you know, similar number of portal triads, 13 versus 10. And the specimen length was slightly longer via EUS, but there was a lot of fragmentation, and that's probably due to the technique. This was a randomized study of IR versus EUS. And although the numbers were, you know, the numbers of complete portal triad were similar between the two, the specimen length was slightly higher in the percutaneous approach. And the length of stay was similar, but the total cost in this study was higher in the EUS approach. We've criticized this study because we think that the technique for EUS wasn't using wet suction, and that's probably where you get better technique with this. And this is sort of our data from Cornell, where we're comparing two different size needles, and you can see here, the bigger the needle, the better the core tissue. And this is early data, and you can see here, this is a five centimeter core. And more recently, we presented this at DDW this year, looking at 48 patients for liver biopsy, and we compared two different types of technique, wet heparin suction, which is the standard, what we call the standard technique now versus the hydrostatic stylet technique, which is a wet suction pull. And basically, what I wanted to show you is that you really can get a high number of accuracy, diagnostic accuracy with a good technique, a high number of portal triads, so 27 versus 21, lower fragmentation rates with a stylet technique, and obviously, you know, fits in with all the diagnostic criteria from the American ASLD to the European and the Asian. So when done properly, you can get a good technique. What about treating varices? Obviously, you can do it with endohepatology and EUS. I'm not going to belabor the point here, but here you can see gastric varices, and you can treat them at the same time. So we all know that the prevalence of gastric varices with portal hypertension ranges anywhere between 70 to 23 percent, compared with 85 percent for esophageal varices. And in the setting of cirrhosis, gastric varices can be seen in at least 20 percent of patients, and they often can bleed, and you can do EUS to do multiple things all at once. So this is a great paper on how to approach patients with gastric varices. It's from Gastro in 2022, and really the summary of this is that you shouldn't do it alone. You should have local expertise and work together in a group, and if that's all you take on from this whole talk, it's all that IR, interventional endoscopy, and hepatology should really and can work together. Obviously, to treat varices, there's a variety of treatments, but I just wanted to focus on the glue and coil treatments. And so this EUS guided glue and coil is where you can see the gastric varices on EUS, and you can coil them directly, and you can inject glue as well. And this is the largest study to date on 152 patients, where you can see that the technical success is nearly 100 percent. You can inject a number of coils under direct visualization, similar to what they do in IR. You don't necessarily need radiology, so we do it a lot of the times in the MICU, and we follow it with what we call a glue chaser, sort of to keep the coils in place to act as a scaffolding. And in this study of 152, they had follow-up on 125 patients with complete obliteration of the varices in 93 percent of cases. And in some patients, you need more than one session for repeat. The adverse event rate is very low with mild abdominal pain, and one patient had a PE. Now, obviously, you can follow up, as I mentioned, but if that doesn't work or if there's shunting, then you really need to know the cause of the gastric varices and maybe involve IR, especially if there's shunting. This is a meta-analysis of 11 studies with over 500 patients, and really, the summary of this is that you shouldn't use either technique alone, but coil and glue, even though all of them have a high number of technical and clinical success, but the rate of adverse events is much lower in the combined approach of glue and coil, and the rate of reintervention is also lower in the coil and glue approach. So, dual therapy is key, and EUS with coil and glue is the way to go. And this is a meta-analysis of sort of newer data with nine tertiary centers essentially showing the same thing. And now, sort of moving on, and Dr. Henry will talk a little bit more about the measurement of hepatic venous pressure gradient, but I want to just bring it back to the other part of what I do a lot, which is obesity. So, we know that over 1.5 billion patients have chronic liver disease, and patients transition from cirrhosis through a compensated to a decompensated stage, and portal hypertension really marks the transition to decompensation. And obviously, to measure the portal hypertension, you're measuring the hepatic venous pressure gradient or the portosystemic pressure gradient, which I'll just now call PPG for ease of saying that. So, we know from our IR folks the different types of measurements, and really what's important here is that the difference between the two is the portal pressure gradient, and less than five is normal, six to 10 is sort of elevated but not clinically significant, and more than 10 is clinically significant, and that's where you get varices, and more than 12 you get variceal bleeding or ascites. And if you reduce the gradient, you reduce the risk of death. And so, looking at this in a different way, you can see the histological gradients also going from the clinical sort of non-cirrhotic compensated and decompensated, and these are the pressure gradients that I mentioned. So, sort of looking at this differently, if you decrease the portal hypertension gradient by at least 20%, it decreases the risk of variceal bleeding, and as a subsequent of that, the risk of death. So, it's important to measure it well, and these are a few studies that basically look at the outcome for this, and I'll mention them in a little bit. So, the limitation of the current practice is that we're doing it via IR, we're not accurately measuring the portal pressure, we're measuring the portal vein pressure, we're measuring a wedge pressure gradient, which in patients that have either sinusoidal or presinusoidal causes for portal hypertension, it may underreport that. So, the other question, which is the obesity question, is how reliable is your standard measurement in patients with NASTRID or cirrhosis? So, this is a study that was done with liver biopsies and hepatic venous pressure gradient measurements were collected at screening and at one and two years, and during the follow-up period of a mean of 2.6 years, about 19% of patients with compensated cirrhosis at baseline experienced a liver-related decompensated event, which included ascites, hepatic encephalopathy, varices or variceal bleed, and some people experienced a two-point increase in their CP score or an increase in their MELD and resulting in death. 14% of patients who developed a clinically significant event had an HVPG measurement of less than 10 four months prior to the event. So, this then led to the question is how accurate is it in patients with NASH? And so, what they decided to do is at the time of a TIPS measure the actual pressure in the portal vein. And so, what they found is that in the NASH group compared to the control group, the agreements between the wedge hepatic venous pressure and the portal pressure was terrible essentially. So, there was a disagreement between the two groups versus 37% versus 14%, and it was mainly due to an underestimation of the portal pressure gradient by at least five millimeters of mercury. And so, in unilateral and multivariate analysis, only the NASH etiology was associated with the disagreement, sort of suggesting that when you're doing HVPGs in patients with obesity, you might be underestimating their gradients. And so, what can we do about it with EUS? And so, here is using EUS you can get these gradients directly. So, you can insert a needle both into the hepatic vein and into the portal vein directly and measure the pressure gradient. So here you can see a needle going into the hepatic vein and a transfuser giving you three different measurements. So you take the average of this and it's 13 and then you go into the portal vein and get a similar measurement and then you minus the two and you get obviously the difference. And in the initial studies you can see that the portal pressure gradient correlated again with patients with high risk with cirrhosis if it was high versus low presence of varices and the pressure of portal hypertension as well. We looked at our data and we showed that again there was a correlation with liver biopsy and KPA. So the higher the portal pressure gradient was the higher the FIB4 score and the higher the elastography score. And this is a multi-centric experience again showing similar data to this again showing good correlation with the portal pressure gradients and the score. And finally this is a study showing from the Brigham that was just published a few weeks ago showing a good correlation between weight loss and improvement in portal pressure gradients. These are patients with NAFLD with at least an F2 score on the FibroScan. 45 patients were enrolled. You can see at 6 to 12 months following a weight loss technique with suturing they had everything improved. So the FibroScan with the FibroScan you can see that the fibrosis improved and also they did liver biopsies that also showed again the scoring improved. They also looked at the non-invasive outcomes and again they all improved with weight loss. But what was more important and this was the first time that this was done with weight loss showing an improvement in portal pressure gradients between zero and six months with improvement in weight loss. So there are future rules for PPG. You can assess response to beta blockers, assess response to antiviral agents, pre-surgery, post-surgery in liver transplant patients and do a one-stop shop for the diagnosis of these patients. And this is a case report that I had and it's not letting me play properly but maybe it will here. This is a patient who presented with obesity and hyperlipidemia. And so we did a FibroScan on them. We did an endoscopy to look for varices. And then we did elastography via EUS and again showing the same thing. So here you can see a KPA of 14. You can get 10 measurements with that. And then this is the setup of the portal pressure gradient. And you can see here that the portal pressure gradient was measured a few times and you can use the Doppler again to see it. So this is the hepatic vein and you put a needle into that and get the measurement there. And then you can go into the portal vein and you can see that the flow for that to sort of tell you that you're actually in the portal vein. And finally, you can do a liver biopsy at the same time. And this is us when we were doing the Heparin technique and you can see in real time sort of a big core of tissue. I tried to write my name but it wasn't possible. So this is just, you know, a few highlights on how to use EUS and hepatology to sort of marry the two techniques together. Thank you so much for your attention. I'll happily take any questions as well. All right, I am going to say that. Move into my talk. And then, and can everybody see the actual presenter view? I never quite know. Yeah, perfect. Okay. All right. So that was excellent. Just basically switch the display. Okay, sorry. Okay, there we go. All right, hopefully that'll work now. So, you know, just an excellent talk of kind of the kind of different, different just fun things you can do with EUS. And I want to talk a little more about how it relates to our patient presentation and as a hepatologist, kind of how I use some of this information when I'm thinking about decision making of when to do this. So, first, just, I don't have any financial disclosures. I did just want to say I participated in some educational sessions for Cooke, but they were unpaid. But I do think that's pertinent. And then, so to get back to our case, you know, we have a 55 year old woman, she has metabolic risk factors, certainly kind of predispose her to, to not be able to to Nash or what we are now calling steatotic liver disease. And so could potentially have a reason to have cirrhosis. She had this breast cancer diagnosis two years prior and had gone through chemotherapy and radiation for that, and is now having what appears to be recurrent bleeding, not severe bleeding with hematemesis or life threatening hemodynamic instability, but it is recurrent and needs to be evaluated. And so again, coming back, I have to ask myself, you know, the, the ultrasound might be suggestive of cirrhosis, although a nodular liver contour doesn't always mean cirrhosis. She doesn't have any overt signs of it on exam. Her labs are really not terrible. And so when I was asking myself, what should I do for this? The easy answer is an endoscopy. So she was sent to me for, for GI bleeding and, and possibly a suspected gastric varix, but I don't really have a good reason right now for her to have portal hypertension, or at least I don't have a confirmed reason. So I'm also thinking in my head, am I going to need a liver biopsy? Is a pressure gradient going to be helpful in this case and, or with her metabolic risk factors, is any elastography even going to be important? And so beyond the endoscopy, I want to start with the liver biopsy. So asking myself, do I need this? And, and we just got an excellent review on, on kind of the importance of a liver biopsy and what we need from it. So as hepatologists, when we're doing biopsies, most of the time we're doing it for one of two reasons. We're either trying to assess an etiology of chronic liver disease, sometimes acute liver disease, or to assess fibrosis, or in some cases to do both in one, in one procedure. Less often, but still used to assess treatment responses, whether it's autoimmune hepatitis, treatment of rejection in a post-transplant patient, et cetera, or even weight loss in a, in a steatotic liver disease patient. The key though, with liver biopsy, as was mentioned, is we need it to be an adequate sample. And so from our own guidelines, it's recommended to use a 16 gauge needle and have a two to three centimeter in length sample. But more importantly, the reason that that, that those specific sizes are mentioned is because we need the, the portal tracts. Generally 11 portal tracts or more is considered to be an adequate sample to get a diagnosis. And, and even with percutaneous liver biopsy, this can vary. And, and just to show you, you know, this is a study from a while ago now, about 20 years ago, looking at patients with viral hepatitis and trying to assess essentially the size of the biopsy on their ability to grade and stage disease. And all of these biopsies were over three centimeters in length and were done with a 16 gauge needle. And so we're 1.4 centimeters in width. And what they did is they slowly cut the biopsies down in size. So they read them all at their normal size, cut them down to 1.5 centimeters, cut them down to one centimeter. And what they found is the biopsy got smaller, they were less likely to find advanced disease, or as this table shows, more likely to find milder stage of, of fibrosis and milder grade of inflammation. They showed the same when they looked at width, when they cut it down from 1.4 millimeters down to, I'm sorry, 1.4 centimeters down to one centimeter, you also lost some diagnostic accuracy. And so, and that's even just the difference between using a 16 gauge needle and potentially an 18 gauge percutaneous biopsy needle. And so as we look at any modality of liver biopsy, this is kind of what we're looking for is kind of size, but also portal tracts. For our patient, as far as what we need, I definitely need the first two, you know, based on her presentation, like I said, she could certainly have steatotic liver disease, but I'm not certain about this. Her biochemical workup for etiologies of liver disease was otherwise negative. And I also want to assess for fibrosis, since it seems like she has portal hypertension based on these outside reports. So EUS guided liver biopsy compared to percutaneous liver biopsy. Dr. Shara just showed you some great studies comparing these. This is actually kind of a systematic review just published actually earlier this year that tried to combine these studies as much as possible. And you can see here for portal triads, the percutaneous liver biopsies, which is kind of the right column of the red boxes, did come in a little higher, or a little more portal triads than the EUS guided, but for the most part, the EUS guided liver biopsies did produce more than 11 portal tracts. And you can see all of these studies are from relatively recent from 2020 to 2021, which is important because these EUS guided liver biopsies for the most part did include the newer techniques, the modified techniques that Dr. Shara was bringing up about liver biopsy, because that has changed over the years with EUS guidance. And the biopsy specimens now are getting much better. I can tell you just from our anecdotal experience here at UVA, that's definitely been the case. When we first started doing them, they were very poor. And just with better techniques in the last few years, we're getting really good samples now. On the right, this is just kind of the total specimen length. And you can see similarly that the percutaneous liver biopsy slightly outperforms in general EUS. But the EUS guided liver biopsy, again, pretty much meets the standards that we need to make a good and accurate diagnosis. So the other part of this is also looking at side effects. And so that top box is actually looking at EUS guided liver biopsies. And this is a study, kind of a pooled analysis. And you can see on the far left over here, overall adverse events pretty low at only 2.3%. But when you look at doing these biopsies using an FNA needle, and it's not really an FNA, it's still a cord, but it's using this 19 gauge needle, you have great diagnostic yield, you have very low rates of insufficient specimens, and actually pretty low rates of adverse events, which compared to down here at the bottom percutaneous liver biopsy, they're pretty equivalent as far as adverse events go. So that being said, though, I have to admit, in most cases, if I'm considering an EUS guided liver biopsy, it's probably in place of transjugular approach, as opposed to a percutaneous approach. If I have a patient who just has elevated liver enzymes, and I'm trying to confirm or assess the etiology of disease, I'm probably just going to do a percutaneous liver biopsy, because in that patient, they don't otherwise necessarily need an endoscopy. A percutaneous biopsy is still kind of our gold standard. And so in most cases, I'm thinking EUS guided liver biopsy anytime I would have formally thought transjugular approach. So how do those compare? So this is a little tricky. This is not a direct comparison. This is essentially two systematic reviews, one of EUS guided biopsies and one of transjugular liver biopsies, and trying to kind of informally compare the results of these. And so, you know, at the at the top, this this darker box up here is kind of the results of the EUS guided biopsies. You can see again, specimen length in general, pretty good. A few of the studies had smaller samples, but these were also some of the older studies, using kind of older techniques and needles. Same with this, the portal triads, or portal tracts, for the most part, pretty good. A few that were very low, but again, using some of the older techniques, as we just saw on the previous slide, these newer techniques, you actually get much better samples and much more higher portal triad, portal tracts, complete portal tracts. However, I would like to show that down here at the bottom, you can see this kind of this is kind of a pooled result here using this true cut needle that's being used a lot for the transjugular liver biopsies, is that the complete number of portal tracts are actually pretty equivalent to EUS and maybe even a little lower when compared to our modern techniques. And so although there's no direct comparison, using a very loose, informal comparison, at a minimum, I'd say they're equivalent. And it may be that EUS is actually outproducing the transjugular liver biopsy in forms of adequacy of specimen. And then again, looking at side effects, the total side effects for transjugular liver biopsies are about 6.7%. If you look further down, most of these are minor. And in general, significant hemorrhage, arrhythmia, et cetera, is pretty low. And again, pretty comparable to EUS. So again, thinking about biopsy, you know, in the last few years, having newer instruments and newer techniques with EUS guided liver biopsy is actually producing pretty good results. They are often a smaller gauge and therefore a little thinner, but typically that's made up for in the length of the specimen. And so in many cases, you're still getting 11 portal tracts. I will say again, percutaneous liver biopsy is still probably our, you know, our gold standard in most cases. But as Dr. Shreya showed, there are a lot of times where we're already needing an endoscopy. And this might be a reasonable technique to kind of combine all of these into one procedure. I will say, I think that EUS guided liver biopsy is at least equivalent and maybe superior to transjugular liver biopsies as far as kind of length of specimen, fragmentation, as well as numbers of portal tracts. And so, you know, nowadays, anytime I'm kind of in that mindset of what I used to say, well, I would do a transjugular liver biopsy, I'm now asking myself, well, maybe I should be doing this under EUS instead. And so if we think back to my case, so my patient who I'm trying to figure out both etiology of liver disease and fibrosis, I think in this case, I've also added on that I would like a liver biopsy. I do think it would be helpful at a minimum to assess for fibrosis and know if she has underlying cirrhosis or not. So now the question is, do I need an HVPG? And again, we've kind of reviewed this, but, you know, we have these specific cutoffs for HVPG that very much relate to our clinical outcomes that we care about in patients with cirrhosis and portal hypertension. And so we have patients with early portal hypertension, we have patients with clinically significant portal hypertension, and then we have our patients who are decompensated and at higher risk to, for death and for further complications. And, you know, this data goes back a long way. So this is one of the earlier studies with HVPG looking at a group of patients with alcohol related cirrhosis from, you know, the early and mid 80s. And you can see in these two graphs, just on the left, varices present and absent, and more importantly, on the right, bleeders and non-bleeders that we're already kind of detecting the cutoff of 12 millimeters of mercury here for HVPG as a good predictor of having varices and a good predictor of those varices being at risk to bleed. You can see even more pointed here, the bleeders had a statistically significantly higher HVPG up around 20 compared to non-bleeders as well. And so this was kind of some of our early data with HVPG, you know, building on that, you know, we introduced beta blockers. And I say we, the field of hepatology, introduced beta blockers as a potential way to decrease the risk of bleeding from varices. And we were able using HVPG to find specific cutoffs for an HVPG that we should aim for. And specifically using these studies with propranolol found that decreasing HVPG by greater than 20%, but ideally to an HVPG less than 12 millimeters of mercury, really reduced the risk of a patient having re-bleeding after their initial event. And so again, just kind of illuminating where HVPG is an important aspect in what we do every day. Beyond varices, we also know that HVPG can predict development of ascites, predict long-term survival, even predict development of SVP and potentially HRS. And this again is a study using propranolol where they looked at responders versus non-responders using the HVPG. And we were able to prove all of this. And I also think it's important here to point out in this study, there were only 28 responders, 45 of the patients were non-responders. And the reason I bring this up is because having potentially a way, not just to check an HVPG or a PPG, which I think physiologically, hopefully we can consider them interchangeable in the future, but also checking at once is good, but being able to treat a patient and assess response in potentially a less invasive way than repeating a transvenous HVPG might be something that we can use in the future when we're trying to titrate beta blockers, assess response to beta blockers, assess need for something like early tips, et cetera. And so, you know, potentially the EUS version might give us more access to this in a real-time manner than what we're used to now. you know, lastly, this was a study again, looking at, um, HVPG as a predictor of decompensating event. And I'm just putting this up here to show that multiple different models, HVPG stands out. And so we all know this, this is a strong predictor of decompensation. More importantly, this study also reaffirmed our kind of cutoff of 10 millimeters of mercury as kind of that good cutoff of what we call clinically significant portal hypertension, where patients that have an HVPG less than 10 have a much lower risk of decompensating over time compared to those with a higher HVPG. So this is obviously one of our most useful clinical tools. We currently use a transvenous approach with balloon occlusion, um, which correlates pretty well to the portal venous pressure. Some limitations of this transvenous approach is just some patients it's undesirable, um, having their jugular vein punctured to do this. It might miss out on presinusoidal portal hypertension by using the balloon occlusion of the hepatic vein. Um, if you do find clinically significant portal hypertension, that patient ultimately may need endoscopy to screen for varices anyway. Um, and just simply access, then the United States, this is done, um, almost exclusively by interventional radiology. And so depending on your area, you may have somewhat limited access to that resource. So then what about EUS? Well, for EUS PPG as a hepatologist, I have to first say, does it compare to clinical outcomes? So do the results I get with a PPG compared to what I see clinically as far as decompensations, um, ascites, varices, et cetera. I would also very much like to compare it to the classic transvenous HVPG and understand that they correlate well, um, uh, and that we can either use the exact same cutoffs or a modified, um, uh, version of our, of our standard cutoffs to predict decompensation, death, bleeding, et cetera, like we've been able to do with HVPG. We need to know what the impact of sedation is. I will come back to that. Um, and then I need to know just generally in what scenarios is it helpful? Is it just anybody that would undergo a transjugular or transvenous HVPG? Are there other indications beyond that where I should be using it? And then ultimately at the end of the day, and I don't really have data on this yet, it's just cost and value of the procedure. If I'm combining procedures, that's great, but is it really saving the patient money and time? And so, you know, again, some of the data that was already presented, this is kind of early animal data, um, that was comparing the EUS guided, um, uh, pressure measurement to a transjugular pressure measurement. You can see what these are values showed incredibly high, uh, correlation between the two, um, during the same procedure. And then as Dr. Shreya already showed, you know, looking at clinical outcomes, as I said, it has to kind of support and, and, um, show correlation. And it seems to in patients who had a kind of pretest, uh, probability for a high risk of cirrhosis versus low risk that kind of bore out with the PPG measurements as did the presence and absence of varices and the presence and absence of portal hypertensive gastropathy. Um, but this is from kind of the early data from, from seven or eight years ago. And, uh, Dr. Chang actually, after doing many of these up to close to a hundred, I think actually went back and pulled all of his data again, um, and then published this. And after six, seven years of doing this pretty consistently, they continue to show, um, good correlation between the PPG measurements that they're getting, the gradients that they're measuring and, um, uh, clinical symptoms of portal hypertension, whether it be thrombocytopenia, varices, portal hypertensive gastropathy, et cetera. And this is, again, one of the things that we need now, I do think it's important to address the sedation issue. So, um, most in most cases, I think at all, I should say EUS guided PPG is being done with at least moderate or deep sedation. And in some cases, even general anesthesia, whereas generally, uh, the transvenous HPG is done with little to no sedation, um, either very low doses of midazolam or none. And the reason that is, is shown here on the left, looking at, uh, transvenous HPG, um, at the top is with no sedation, the circles in the middle are with very mild sedation and even just a small increase, um, from 0.02 to 0.03 mix per kilogram was enough to, to drop the HPG almost by two points. And the point of this was to show that the lower dose of midazolam for a transvenous HPG probably isn't going to change the gradient that much. And if needed, it is okay, but sedation does have an effect on this. They looked even further again, this is transvenous and showed that when you use deep sedation with, with propofol plus or minus fentanyl, um, you also can see some changes. And so the column on the left, um, shows kind of awake, unsedated, they measured the HPG and we're just going to look at this top a section and then going to the right is with deep sedation. And what I'll point out though is yes, if you look at the individual numbers between the free hepatic vein and the wedge to paddock vein, you will see variation between inspiratory and expiratory pressures, and even the mean pressure. But overall, when you look at the HPG, um, they're not significantly different from when it was measured when the patient was awake. Um, and it's, it doesn't mean that this is irrelevant, it, it is not, and this needs to be looked at with EUSPPG moving forward and we need to further evaluate the effects of sedation. However, um, it may be that kind of both ends, both the free and, or the hepatic venous pressure and portal pressure are changing similarly so that we're seeing kind of similar drops into the overall HPG isn't changing very much. That being said, it is important. It's something that we need to consider. Um, but like any new methodology, there are going to be growing pains. Um, you know, this is from 1979, you know, even when they were first doing balloon occlusion, instead of just kind of, um, uh, direct wedged catheter and, and one of the first things that they did is they looked at the balloon occlusion and then they compared it to the direct portal venous pressure and found an excellent correlation, um, just like we've done at least in animal models. And I'll show you even between those two techniques, you can look at the HPGs and there is difference. If you look at each individual patient, there is some variation between these two measurements, but when you look at the bottom overall, the pooled results are really not that different. And I think that's what we're seeing, you know, similarly with deep sedation, um, versus being awake. So again, something we need to look at, but overall, uh, potentially something that's easily to overcome. We may just need to define slightly different cut points for what we're defining as clinically significant portal hypertension, higher risk to bleed, higher risk for death, et cetera. And I will make a statement that study is ongoing right now, primarily in Europe where they're doing direct comparisons in a human cohort, comparing US PPG results to trans venous HPG. And hopefully that data will be published later this year or early next year. So let's go back to our patient. We have a 55 year old woman. She's got recurrent mild GI bleeding, some melanin, some anemia, no overt, um, hemodynamic instability kind of bleeding. She's got risk factors for Nash, but no overt signs of cirrhosis. And so we sent her for EGD and EUS guided, uh, PPG. So here's our endoscopy results. You can see her esophagus looks pretty good and her stomach. And this took us a second to really see this. She does have a small variceal complex here, kind of along the greater curve of her cardio fundal region. And up here, this very small looking varix actually had a little flat high risk area. And this was our suspicion at the time of what might've been bleeding. And so when we did our, our, uh, gradient measurements, we measured the middle hepatic vein and kind of the average result was 9.6. The portal vein was 24. And so we got a gradient of 14.4, which is well beyond clinically significant portal hypertension. And it would potentially explain, um, developing varices and bleeding. But at the same time, we were also able to do a liver biopsy all in this one procedure. And so on top of that, we have a biopsy that shows patchy areas of the thickened hepatic plates, hepatocyte atrophy, suggestive of NRH, a reticulant stain did confirm this. We did not find any fibrosis. And ultimately we're able to determine that her trastuzumab that she was taking for her breast cancer had probably led to NRH and non-steroid portal hypertension. It is a relatively common cause of that. Um, and so we had her hold that. Um, this was done a few years ago. I didn't have any cross-sectional imaging. So we did end up doing that and found a gastro renal shunt and proceeded with BRTO to treat her GV, but we could have done an EOS guided cyanoacrylate injection with or without coils in that moment and potentially not only diagnosed her, but treated her all in one procedure and just been, have been completely done after that one case. And this is what it looked like later. So we've done this now multiple times, um, over the last few years, kind of following up. Um, the gastric varix is gone. You can still see, she has some portal gastropathy. Her esophagus still looks pretty good. Um, she did have to restart her trastuzumab, but we're just kind of monitoring her portal hypertensive symptoms, um, and, and it's been pretty minimal follow-up for her, um, as far as what she's needed for that. So kind of some conclusions from all of this, and then we'll take some questions. Um, so endohepatology, so determining portal hypertension of cirrhosis, but also like as in our case, pre sinusoidal portal hypertension, um, EOS guided PPG can do that. Um, determining whether or not patients have clinically significant portal hypertension for preoperative concerns. We didn't get into this too much, but we know from HCC data that if you have an HVPG less than 10 millimeters of mercury, you'll do much better with the hepatic resection for your HCC than if it's greater than or equal to 10. And these cutoffs have already been published as kind of correlates for bariatric surgery patients. So as our, uh, uh, number of patients with cirrhosis from steatotic liver disease continues to balloon, um, that will eventually potentially need liver transplants, being able to catch them when they're compensated and when they don't have clinically significant portal hypertension to do say a sleeve gastrectomy is a really good time to try to get to them. And since they really all need a preop EGD anyway, you can do EOS PPG. You could just do elastography. You can do biopsy again, all in one procedure. Similarly, we've, we've been doing this quite a bit for our kidney transplant patients who have compensated cirrhosis to try to determine whether they need kidney alone versus SLK. And it's been helpful for that similar to what we used to use trans jugular HVPGs for, um, you know, in the longterm, we do need some more data. I do think ultimately it could probably be used in place of any indication for a trans jugular HVPG. But before I say that, or rather before I can prove that we need to see these upcoming studies doing direct comparisons between the two modalities. We do need to understand how sedation may affect them. And we need to continue using studies, whether it's large cohort studies, multi-center studies, looking at PPG results and clinical outcomes as well. So I will stop there and say, thank you very much for letting me take part in this. And we would be happy to take any questions. Thank you both for really fantastic talks and overviews. I think you summarized the literature incredibly well. We have three questions. The first question is directed to Dr. Shreya. Do you do all of your direct portal pressure gradient measurements under general anesthesia? So, so great question. I guess Zach touched upon this a little bit. Yes, traditionally, although we're trying to move more towards propofol based sedation, we haven't noticed any difference in the, in the, in the measurements in those. The key thing is to have a CRNA who's comfortable at really sedating the patient, because you don't want to be sticking a vessel and then the patient moves, but it has been okay with propofol. It's just the comfort of the anesthesia team that's with you. Then to Dr. Henry, you mentioned that you would consider USPPG. This by the way, is from Dr. Nabil Wahid, biopsy in any patients you would have previously considered transregular pressures in biopsy. Is it practical to do this without overwhelming interventional GI with referrals for these? Perhaps that could go to Reem as well. Do you want to be overwhelmed? And has UVA created a clinical protocol for referring patients for USPPG biopsy? Yeah, so that's an excellent question. So I'm probably behind the eight ball because I have not created a clinical protocol. I think when we started doing this two years ago, a little over two years ago, it was relatively still kind of an unknown and all of our referrals were internal. But when I say internal, I mean internal like for me, it took me a while to get my, my hepatology colleagues to refer. But even internally, we're getting referrals, direct referrals from some of our hepatobiliary surgeons before they do hepatic resections from the kidney transplant team. And so as of right now, no, they haven't overwhelmed them. Or at least I work with Vanessa Shammy here at UVA. She hasn't told me she's overwhelmed, although she did three of these today. So I do think having a clinical protocol with some cutoffs is helpful. I think as a hepatologist, that's where I think it's my responsibility to work with our interventional colleagues to try to outline some of those scenarios that I just mentioned in my talk of these are the patients where I really think this can be helpful right now. And I do think there's some patients that are probably borderline where we probably need some more data on like whether or not it's really useful. I think the surgical pre-ops, it can be very helpful, definitely when we're trying to rule in or out cirrhosis, non-cirrhotic portal hypertension, et cetera. But I don't have a written clinical protocol right now. So I'm glad you asked, I need to write one. And then there's a question from our fearless leader, Dr. Aki. Can you talk a bit about the cost of EUS guided pressure measurements versus a HVPG? I cannot. Only because I'm unqualified to do so. I don't fully know what the cost is of the EUS PPG, Reem, you may be able to give some insight into that. It's around $2,000. But I think the real question is because there was that cost study with EUS guided versus IR and EUS guided when you're using it in an OR endoscopy room will cost more. The question is, are you doing anything else with that? And then hopefully you can bundle that cost together. So you're getting one anesthesia, but you're doing an endoscopy, an EUS, fibroscan, a liver biopsy and a portal pressure gradient all at the same time, it will be more cost effective, but we'll need to do those studies. So there's nothing out there yet showing those. Yeah, and I'm not the impending study that, again, hopefully within the next six to 12 months, we'll get published doing the direct comparison between PPG and transvenous HVPG. I'm hoping it will have some cost data associated with it. I don't know that that was originally part of their study design. So I don't know that they're like prospectively looking at that. But I agree 100%, Dr. Rocky, it needs to be always right. Cost is always part of this process. And I also think, though, the more we do it and the more efficient we get at it, generally over time, costs can come down as we get more efficient with these procedures. And then I have a question about pediatrics. I'm not sure if either of you have pediatric experience, but where this sort of thing comes up all the time is in the, or somewhere assess a polycystic kidney disease, for example, where people have congenital hepatic fibrosis and significant portal hypertension, which is often underestimated, and then they need a kidney transplant. Would this be aware of staging liver disease? And is this something, has pediatrics been explored at all? I'm not aware of any data with PPG in pediatric patients. And in polycystic liver disease might, specifically, might be a tough one to do sticking through the stomach and trying to access without hitting assist. But I mean, I'll speak to the expert as far as difficulty for something like that. So usually, it's not really the it's the congenital hepatic fibrosis. That's more the issue. Gotcha. Yeah, yeah. Um, I mean, we have done, I can only say, you know, we've our interventionalists, you know, do other interventional procedures in pediatric patients. We have, unfortunately, had to do some cyanoacrylate injections in pediatric patients that have gone well. So there's no reason to think that you couldn't. I think like everything, unfortunately, I feel like we do things in adults, and then peds is five years behind, you know, once it's all approved, and we've done it 1000 times, and we're all comfortable with it. Now, we'll take that risk. So I suspect it'll take time. I think for for peds, the main limitation would be Oh, inopportune, the size of the patient. So if the if the if the patients Oh, sorry, did I? Did I lose everybody? For a second? Yes, repeat. Yes, the main limitation. I know, I was gonna say, I think the main limitation is the size of the patient with peds, because it's the size of the scope that needs to go down. And that would be the main limitation. So they need to at least be, I want to say, at least 15 kilos or more to put down the scope safely. And then you should be able to do it. We're at the top of the hour. And before I hand over the bottom of the hour, so before I hand over to our fearless leader, I want to thank everyone who attended. Thank both of our fantastic superb speakers. Hopefully, we'll come back. And I want to thank all the attendees for making this such a successful event. This will also be available on liver learning within 48 hours. So if you know anyone who missed it, who wanted to hear it, it will be up online within the next two days. Thank you. Thank you, guys. Great job. Fantastic. Thank you. Take care.

endoscopic ultrasound

EUS

portal hypertension

liver disease

liver stiffness

variceal screening

gastric varices

hepatic venous pressure gradient

EUS-guided liver biopsy

transjugular liver biopsy

Kim Foxx