So I'm going to talk to you a little bit about, just to complete the assessment when we see patients with liver disease, and then how we manage portal pressures, not as a hepatologist, but more as endoscopists, and sort of what we can do and how we can do this all around. I'm not able to advance. Okay, so these are my disclosures and the main disclosure in this is that I'm not a hepatologist, so don't expect me to tell you anything else. All right, so when you do the one-stop shop that we just heard about, you're looking for liver stiffness. Instead of doing fibro scans, we're able to do it via EUS. You could do portal pressure measurements, which we heard about, biopsies, but you could also screen and treat for varices. You heard the bleeding talk earlier on, but this is sort of how we do it via EUS. And we're not limited as endoscenographers by ascites or obesity. So it's definitely a hot topic. There's been a rise in publications in the last few years, and you can see sort of in the last three years, there's been a whole host of publications. So as was noted, Ken Chang really developed this field, and he was one of the first to what we call the pillow sign of the liver. So instead of just looking at the liver and moving on to looking at the pancreas and elsewhere, you can look at the liver and see how stiff it is. And based on that, we started looking at the liver stiffness measurement, initially measured through transient elastography, which is the fibro scan, but we can do it through EUS. So EUS initially had the shear wave, the strain elastography SE, which was back in 2003. And more recently, we started doing it with shear wave elastography. And the way it measures, it measures absolute values with 2D measurements by sort of the amount of pressure that the transducer does. In an early study, what it did show is that there is really good measurements in patients with cirrhosis in both the right and the left lobe of the liver with upwards of 96%. And in a study that was just presented yesterday at DDW by Marvin's group, they looked at 54 patients with NASH and NAFLD. And what is important here is that shear wave was the best predictor out of all the non-invasive measurements, including fibro scan in this group, sort of suggesting that maybe as endosynographers, or if you want to do that one-stop shop, it's patients with NASH and obesity that we want to really target. So now we shift from diagnostics to therapeutics. So when you do an EUS or an EGD, you see someone with varices. How do we treat them? Well, we know we can treat them with banding, with endoscopic techniques, IR, and via EUS. Gastric varices can be present in portal hypertensive patients in anywhere between 17 to 20% of patients, in cirrhotic and up to 20% of patients, but they can happen without portal hypertension. And I want to draw your attention to guidelines that were published last year by the AGA, where you really look at your local expertise before embarking on anything else. So if you're able to do it, great, but you should combine expertise with your IR group as well. So management, as with anything bleeding, it's the ABC intubation, blood products, etc. But for EUS, you really need to know the difference in gastric varices between GOV1s, 2s, and whether they're connected to the esophageal varices. And so when we look, and what we're going to talk about is the cyanoacrylate and glue injections, and that's what we can do via EUS. This is a video from Marvin back in 2018. You can see here the actual advantages of EUS. So you can see the varices, and then you can stick the varices with a 19-gauge needle, and then advance coils, which are the same coils that IR use for embolization. And then you can do color Doppler flow at the time of the injection or the embolization to confirm that you have obliterated the varices. You can do this via fluoroscopy, or sometimes you do it at the bedside when you're in the ICU. And then you can follow it with an injection of gelatin slurry or glue, depending on what you have available. And this was a study back from Kenman Moller's group with 152 patients. What you can see here is that the technical success is upwards of 99%. They injected an average of 1.4 coils, followed by glue. The follow-up time at three months showed complete obliteration of the varices, which is great, and it's a really good way of treating these patients that would have traditionally gone to IR. So the follow-up is either at one month to do repeat treatments, at four months to ensure complete eradication. And if you re-bleed or they continue re-bleeding, you should consider doing cross-sectional imaging to ensure that there's nothing else going on. So what do you do? Do you do just cyanoacrylate? Do you do just coils, or do you do a combination? This was a meta-analysis published now three years ago with 11 studies, and essentially what it did show is that the combination group, which is the cyanoacrylate coil, is better than one alone. You can see here that the technical success is higher in the groups, and also the rate of success is higher. The rate of adverse events are lower, and the rate of re-intervention are also lower. So in summary for the acute gastric varices treatment is that although they're uncommon, you can do management via EUS. You don't need to call your IR colleagues, except if you need to, but you can do combination therapy. But you need to ensure that you have good expertise and good backup in your local hospital. So then we move on to portal pressure gradient. So we've heard about the different types of ways you can measure portal pressure gradient. You can measure it via EUS, which is hopefully what I'll convince you is the better way, or via IR, which is the hepatic venous pressure gradient. Now the way IR people measure it is they puncture the hepatic vein, and then they wedge their catheter towards the end to do a wedge hepatic measurement that is a surrogate for the portal pressure venous pressure, and then they have a gradient. What is important that you understand is that when we look at this as a continuum with liver disease, you go from the non-cirrhotic compensated and the decompensated stages is that the more you become decompensated, the higher the pressure is. But you do have a pressure gradient that once it's more than five, that's clinically, it means that you have hypertension. Anywhere between five and 10, it's clinically insignificant, but it probably portends a worse outcome down the line. And so once you get anything above 10, you start having a high risk of varices. Anything above 16, you have variceal bleeding and ascites. So this is sort of what I just mentioned. Anything above 10 to 12, ascites and varices. The severity of portal pressure gradient, meaning if it's above 16, you have a high risk of death. But if you decrease it by 20%, then you decrease the risk of variceal bleeding. Obviously, the risk of hepatocellular carcinoma is higher. It goes up if the pressures are above 10. And the disease progression also increases by up to four years. So you can get, you're more likely to see decompensation if your pressure gradient is greater than 10. So our aim is to reduce the pressure no matter how. And if weight loss is the way, and you'll hear about obesity later on, then that's great. So the limitations of the transdrugular approach is obviously, it's cumbersome, it needs contrast, it needs radiation exposure, but it's also not accurate for patients with obesity. And I'll show you a couple of studies as we're trying to. So when we think of causes of portal hypertension, you have presinusoidal causes, sinusoidal causes, and postsinusoidal causes. When IR is trying to measure the portal pressure, and it's doing a wedge pressure, you're inaccurately going to measure the pressures in presinusoidal causes such as, for instance, sarcoidosis, portal vein thrombosis, primary biliary cirrhosis, et cetera. And so you're going to get a falsely normal pressure or a lower pressure than normal. So there are these groups of patients that you're not going to accurately predict whether or not they have portal pressure, an elevated portal pressure. And so this is a study that looked at this with, is pressure measurement via IR not as reliable in NASH patients? And what they did was they looked at liver biopsy patients that were collected at one and two years, and follow up, 90% of those patients had an episode where they decompensated, they became decompensated either via ascites, bleeding, or death. And of those, about 14% of those patients had a normal pressure gradient as measured via IR. They took this a step further back in 2021, where they compared the wedge pressure with the accurate portal pressure gradient in patients with NASH and compared them with patients with alcohol or viral hepatitis. And what it showed is that there was a disagreement. So in the patients with the NASH group, in about 37% of patients, the pressure was measured as normal or low, when in fact that wasn't, it was an actual underestimation. And so you're four times more likely to have an inaccurate pressure in patients with NASH, sort of another reason why you should really be doing portal pressures. And so this is one of the first studies that was published out there, looking at 28 patients with suspected cirrhosis, and they classified them as high or low. And what the study showed was that in patients with high versus low cirrhosis, you can see that the pressure gradients were different. And so here is the high risk versus low risk cirrhosis. And then the next graph shows the high versus low risk of varices, and you can see that the portal pressure gradient was significantly different. And this is the evidence or absence of portal hypertensive gastropathy. Again, the portal pressure gradient was significantly different between the two groups. Sorry, I think I speak faster than the mouse. So this is our data with 24 comers of all patients with liver biopsies and portal pressure gradients at Cordell. And what you can see here is that we correlated really nicely, that the portal pressure correlated with both the FIB4 and the FibroScan, sort of showing that it's a good surrogate for this. So here at DDW, both Marvin and I were part of a group that prospectively looked at measurements of portal pressure gradients and liver biopsies. And this is sort of the main summary of this is that it's easy, it's simple, everyone can do it, very low side effect profile. So how do we move on this clinically? So we know and we've shown that if you lose weight, your hepatic ceatosis index improves, and that means your fibrosis improves, the NASH score also improves with weight loss. This was done with an endoscopic sleeve gastroplasty, and we published this a few years ago. The Brigham group looked at this with a different placation device and looked at the fibrosis scores measured with a portal pressure gradient and also liver biopsy. And what they showed is that with weight loss, the NFS score, the FIB4, all these noninvasive scores also improved at the 6 to 12 month mark. But again, also the hepatic venous pressure improved, the portal venous pressure improved, and the portal pressure gradient also improved, sort of suggesting a good correlation that when you lose weight, you're going to get improvement in NASH, but you're also going to get improvement in portal pressure gradients. So how do we tie this in all together? At Cornell, and I know at a lot of other places, we have a multidisciplinary clinic for NAFLD and patients with obesity, where they have an integrated approach, they see an on-site GI hepatologist, they get a fibro scan, they get an in-body scan, if they see me, they'll get a liver biopsy and portal pressure gradients, and maybe some procedure for weight loss, or they get medications. So it's important to see that we can all tie it in together in that one-stop shop. And if I can play this video, but Marvin might be able to show it a little bit later, but we'll show this. This is a patient that came in with obesity, and came in with obesity, so had a fibro scan measurement done, and it showed F3 and S3. So we then go in and do an endoscopy, and the endoscopy looks for any evidence of varices, portal hypertensive gastropathy, to see if we can treat it. I don't know if you can advance the video to the sort of dots, that those are the most important parts of the video. What it basically does show is that you can do the shear wave elastography, which we did, and here the shear wave elastography showed a KPA of 14, which is similar to what the patient had on a fibro scan. And then we go in and do the hepatic venous pressure gradient and portal pressure gradient with the Cooke 25-gauge needle, and this is obviously a proprietary needle. It's all in sort of a one-step shop here. In the next few images, you can see us accessing both the portal pressure and the portal vein and the hepatic vein, and you could use Doppler flow to sort of know which vein you're in. And so the sinusoidal approach shows you that you're in the hepatic vein, and then the portal pressure, you can see the portal vein, you can see sort of more of a halo around it, so you know you're in the portal vein. And then after that, you can do a liver biopsy with sort of a modified suction technique, either pull through, wet suction, whatever you prefer, but it has to be a core needle. And hopefully with that, you get good core. And so this is sort of the summary to show you that you can stop the video. You can get everything all in one-stop shop with these patients. Can you move on to the next slide, please? So one-stop shop, you can also assess, which we haven't really talked about because there's very little data, response to beta blockers, response to antiviral agents, and maybe even assess the risk post-hepatectomy for liver failure. There's so many indications for portal pressure gradient and liver biopsy and where we can access them as endoscopists here and not hepatologists in these patients. And so the evolution is to use portal pressure gradient in these patients. You know that hepatic venous gradient is not accurate in patients with NASH, and they may get underestimated. You should be able to do a one-stop shop, talk to your hepatologist. Multiple studies are forthcoming, but we need to collaborate with our hepatologists. Thank you very much.

liver disease

portal pressures

endoscopic ultrasound

varices

portal pressure gradient measurement