We will switch next to Dr. Kenneth Chang from UC Irvine, who will demonstrate an EUS-guided portal pressure gradient measurement, shear wave, and liver biopsy. UC Irvine, you are live on. Maybe we can start with the in-room just for a second. I want to say hello to my illustrious moderators. Thomas, good morning. Ken, Sai, Amit, great to see you all. Can you all hear me okay? Yes. Okay, great. So in my room, I just want to introduce the amazing team we have. So we have Jay, who's our GI tech, Eliza, our nurse, Dr. Mike Perez, our anesthesiologist. And I'd like to introduce my advanced fellow, Dr. Rahim. So Dr. Usman Rahim is a special bird in that he is a board certified transplant hepatologist, and now he's finishing up his advanced endoscopy training. So very recruitable guys. But anyway, he is the perfect person to present this endo-hepatology case. Usman. Hello everyone. Usman Rahim here. So our case is a 75-year-old female who presents with asymptomatic jaundice. Previously, she's been told by other physicians that she had fatty liver. Her past medical history is obesity, Crohn's disease, which is well-controlled, hypertension, actinic and seborrheic keratosis, and surgical history includes cholecystectomy and prior fistulactomy for Crohn's disease. Social history, she does not have any high-risk features, no alcohol use, non-smoker, no tattoos, and no illicit drug use history. And in terms of medications, she takes Herbiceratin, 150 milligrams once a day, and Mercaptopurine, 50 milligrams once a day for over 10 years. Yeah, I just got an update. She's now on a hundred milligrams. I see. So she got increased. Clinical data, her BMI is 35.58 kilogram per meter square. Her total bilirubin is 6.8. Direct bilirubin is 0.8. Alkaline phosphorus mildly elevated at 107 units per liter. AST is 34, ALT 31 units per liter. Albumin, 4.2 grams per deciliter. Her autoimmune labs were negative. That includes ANA, smooth muscle antibody, and anti-mitochondrial antibody. And her viral hepatitis workup was also negative. In her metabolic workup, ceruloplasmin was 17 milligrams per deciliter. IgG was normal at 932 milligrams per deciliter. Ferritin, iron saturation, and hemoglobin are all normal. Her hemoglobin is 13. She does have low platelets of 127,000. It's now 87,000. It's now, okay. So Dr. Chang has more updated news. INR 1.34. Endoscopy done six months prior to her referral to us. There were no esophageal varices and her colonic mucosa was normal and her Crohn's disease was very well controlled. She had an outpatient fibro scan which revealed 22 kilopascal consistent with F4 fibrosis. Outpatient MRI done by referring physician to assess for primary sclerosing cholangitis. There were no PSC changes. The liver was diffusely enlarged and nodular. There were no masses. Spleen was moderately enlarged measuring 16 centimeter. And there were prominent perisplenic vessels. Planned today, we have a patient with isolated total bilirubin elevation. A gradual rise over the past six years. Our differential diagnosis given her past medical history includes NASH or should we say updated metabolic associated stator hepatitis, NASH, versus drug-induced liver injury versus PSC, early PSC changes. We're going to get an updated staging of her fibrosis through shear wave elastography and assess whether she has elevated portal pressures, you know, which may predict future decompensation. So end-of-hepatology workup, one-stop shop, EUS, EGD, PPG, liver biopsy. Thank you. Thank you, Ismail. And tell us about what you found just before camera, on camera. Right. So we just did an endoscopy. She does not have any esophageal varices. Retroflexion view of the stomach does not show any gastric varices. And mucosa, there are no mucosal changes consistent with portal hypertensive gastropathy. So overall, a completely normal EGD examination. Thank you so much. Okay. I just wanted to pause just for a second because the, you know, these liver cases can be a little bit more complex and nuanced. So I just want to hear from the moderators of the audience. Any questions about the case? You know, what are the moderators? What are you thinking? What are the possibilities? What are the likely diagnoses? And then we'll get to the case. Any thoughts on the case itself? And we can switch off the PowerPoint. I thought it's interesting that bilirubin is elevated because usually for mastoid or MASH, usually bilirubin should not be elevated. So, yeah. So it is unusual for NASH or MASH to have these numbers. Absolutely. So, Sai, what do you think? You think it's DILI? It's going to be DILI, but we'll see. But also, fibroscan is 22 kilopascal, and I feel like that is going to be falsely elevated because of the BMI greater than three, looks like. So I think that might explain why on EGD we do not see varices or portal hypertensive gastropathy. Yeah, so there's splenomegaly, there's some dilated perisplenic vessels, but no gastric or esophageal varices. So it's a mixed picture, but down-trending platelets. So synthetic functions are going down, up-trending INR. So it's certainly concerning for ongoing deterioration of liver function. So cirrhosis possibly on the way to decompensation, but she feels absolutely fine. She has no symptoms, not even pruritus. OK. Any other thoughts from the panel? Ken or Thomas, we're good? We're good. We look forward to your demonstration because I think it'd be very valuable to evaluate the portal pressure gradient in the case like this. OK. Thanks, Ken. So I think you're seeing the EOS image now? Yeah. Is it OK? Do I need to brighten it for you or we're good? Oh, it's good. OK. Thank you. All right. So we're looking at the left lobe of the liver. I'm going to take a look at the liver edge first. The reason for that, I'm looking for any blunting of the liver edge. And I would say, I would say based on this very mild initial blunting, you see the angle of the liver here, a normal, normal liver will drape in the same contour of the gastric wall. And this is coming off a little bit. So I would say very mild, subtle blunting of the liver edge. Then I'm going to look at the liver contour, the liver surface. And if you follow my arrow, you can see that the liver surface is not perfectly smooth. There's some undulation of the liver surface. Maybe here it's getting a little, a little lumpy bumpy right in here. So there is some signs of some possible nodularity. At least they're early. I'm looking for a trace ascites. I don't see any ascites. And then on the liver parenchyma, I'm looking for typical signs of either steatosis or regenerating nodules. So as I just look at the liver parenchyma echo texture, I see a little bit of a little bit of subtle beginnings of some possible regenerating nodules, maybe this one. But, you know, maybe here, but extremely subtle. But at least our eyes are telling us this isn't normal, right? This is not our normal liver. There's something it's heterogeneous. And there are these little areas that are, you know, possibly early regenerate nodules. So so far, just based on five seconds of imaging, this is not a normal liver. And I think we can say that. Then the next thing we want to do is we can perform a shear wave elastography. And shear wave elastography is essentially ultrasound guided fiber scan. There is a push pulse wave that comes out through the same transducer while the imaging wave is going on. The push pulse wave punches a sound wave into the liver and it sends a secondary wave, which the transducer can calculate the speed of. The faster that secondary wave caused by the push pulse, the faster the wave is moving, the stiffer the liver. And so that's how we get our liver stiffness. And it's in kilopascals. So I do want to show you shear wave elastography because it's part of the Arrieta processor. It's part of most of our EUS units. And it's a pretty quick and noninvasive way. And we can measure the left, the right lobe, just like in with a fiber scan. But we can also measure the left lobe, which is hard percutaneously to measure the left lobe. And we can measure the spleen stiffness, which cannot be done by percutaneous routes that can only be done by MR elastography. So we have an advantage in we can sample bilobar as well as splenic stiffness. So I usually like to go to the right lobe to measure my first shear wave. So I'm advancing the scope through the pylorus right now just to get some imaging of the right lobe. I'm trying to gently get this through the pylorus. That'd be funny if I couldn't. I'll angle it. Okay, I'm in the duodeal bulb. And so here in the bulb, I'm imaging the liver. So the idea with shea wave is you want to have very good acoustic coupling, but you don't want to compress the liver with your transducer because you can very easily artificially create stiffness by compressing the liver with your transducer. So here I have a decent non-compressed view of the liver. So I'm looking here, I am not compressed, my transducer is not pushing on the liver, and that's the only, you know, subtle kind of technical consideration for shear wave. So now I'm going to turn on the shear wave button and I'm going to put my, this is my region of interest here, and then once I'm in a stable position, I just hit the button update. And so I'm getting a E-value of 34.52, which is extremely high, and the VSN is 91%. The VSN has to do with, within that two centimeter box, the transducer was able to get good information on 91% within the region of interest, so that's a good number. We wanted it to be at least over 50, so 91 is excellent. So what I'm going to do is I'm going to get a few passes here. So now I'm getting 23. Now I'm getting 19. There's 29. There's 24. 21, and we're getting 100%. I'm going to get two more because the first two, I think I got some duodenal fluid that may have interfered with the assessment. So I'm going to do two more, and that'll knock one and two off by doing 11 and 12. No, I think I'll do one more. Okay, so now I've done 10 passes, and I'm looking at my chart on the right. I'm looking at all the E values, and it's telling my mean score is 25.0, which is very similar to the Fiberscan score of 22. And then the VSN is 2.89, which is the mean. And then the interquartile range divided by the mean is only four, and we like it to be less than 15. That tells me my numbers are very tight relative to each other, and that makes a more reliable score. So this is about as reliable as you can get with the VSN being 100%, except for one at 99. My dad would be upset at me, Asian dad. Why didn't you get the 100? But anyway, so we've got 10 good passes at nearly 100%. So this corroborates the Fiberscan. I also measured the left lobe before we came on camera, and it's pretty much the same number. Eliza, what did we get for left lobe? We got 22.4 in the left lobe. So very, very, very similar right and left lobe. Sometimes we get a little bit of discrepancy, but not a whole lot. So that confirms her liver is stiff. So now we're going to go to the spleen and measure the splenic shear wave. Any questions on shear waves so far? Dr. Chang, as you're transitioning, we'll quickly go to Orlando Health and we'll come back to you in a few minutes. Okay. What's the plan now, Ken? Yeah, so I showed you the shear wave of the right lobe. I won't bore you with the left lobe, but I do want to show you the spleen, and then we'll go to the portal pressure measurement. So this is the patient's spleen, quite enlarged. I measured it to be about 12 centimeters. And I do see some dilated tortuous vessels, perisplenic. Let me turn on the color flow here. You can see now there's flow in those dilated perisplenic veins. So she doesn't have any gastric or esophageal varices. And I looked in the gastric submucosa, there's nothing going on there, but certainly we have some perigastric vessels. So that corroborates the MRI findings. So in terms of, and there's also a small accessory spleen right here. So I'm going to show you the shear wave. So I've hit the SWM, the shear wave button. And again, I want to find an area where I'm getting good imaging, but I'm not compressing. So if I compress like that, that's too much. I need to back off, relax, and then put my box about there, and I'm not compressing. So I'm getting 43 kilopascals with a 72% VSM, which is very good. And I did the whole spleen while we were off camera, so then I can show that to you. And this was the number that we got of the spleen. This was the number that we got of the spleen. So the median was 44.93, shown right here. So in our studies, because there haven't been much studies looking at shear wave of the spleen. So we did a study comparing the spleen stiffness with liver biopsy and portal pressure measurement, and we determined a cutoff of 25. Above 25, the spleen is too firm, and is suggestive of portal hypertension, and certainly her spleen is 44. And the nice thing is, there are things that can attenuate your measurement of the liver, fat in the liver, fibrosis, obviously can affect your stiffness, but there's nothing that can affect the stiffness of the spleen other than pressure, unless there's infiltrating granulomatous disease, or lymphoma, but aside from those zebras, the spleen, if the spleen has increased stiffness, that's from elevated portal pressure. So it's a very clean way of measuring surrogate for portal hypertension. So we do right lobe, left lobe, and spleen. So based on that, we're predicting the portal pressure gradient to be elevated. All right, so now any questions on that before we go to the PPG? No, I think everything is clear. It's nice to see after all the interventional work that you sort of get back to the slow motion imaging type of. That's right, that's right. Thank you for that. Yep, there's still some use for us old guys. Okay, so I want to look at the vessels, because obviously I want to make sure my needle goes into the correct one. So I'm here in the left lobe of the liver, which is by turning my shoulder leftwards. And then as I pan right, the first vessel I'm going to see is the left hepatic vein. This is the left hepatic vein. I like to say it's a smiley face of the liver. Welcome to the left lobe. So this is the left hepatic vein, and I can follow the left hepatic vein with my arrow all the way back up to the IVC. So that's the left hepatic vein, there's IVC. Ken, is that necessary to follow it to be sure that's the right one? Not absolutely. There's three ways of confirming. One is by its contour and location. Two is by its connection to the IVC. And three is by doing pulse wave, and you get the typical four phases of the hepatic vein pulse wave pressure. ASVD, and that's, you know, there's no way you can be wrong when you get the pulse wave, obviously. So now if I want to, so that's the left hepatic vein. If I want to go to the middle hepatic vein, I just simply rotate shoulder right, and that's the middle hepatic vein. So again, this is the aorta, and this is the middle hepatic vein, which separates segments four from segment eight. The left hepatic vein separated segments two from segment three. And I like to say that the middle hepatic vein looks like the head of an elephant. This is the elephant's head. This is the elephant's trunk. Maybe there's a tusk here, but anyway, this is the elephant head, a sign of the middle hepatic vein. So this is a possible candidate for hepatic vein pressure. The left hepatic vein may be easier for this case, not always, usually it's the middle. And then the other vein, if I continue to turn right, I get to the IVC here, and the right hepatic vein is right there. So you get a small nubbin of the right hepatic vein here, and that separates segment eight where my arrow is with segment seven, which is the most posterior segment here. So just a quick overview of liver anatomy. So this is- Amit, why would you select the middle versus the left? Left seems to be more accessible, right? Yeah, so I don't know if I said it correctly, but what I meant to say is today for this patient, I'm going for the left hepatic vein. Okay, but you could choose either between the left or the middle, right? Yeah, so I was deciding a little bit, let me just share with you my thought process. So I like the imaging of the middle hepatic vein, however, it's a little bit narrow here, it does widen more here. So this is a nice target, but now I'm also looking at my distance, and that's quite a bit, and that may almost be at the end of my needle throw. And then getting it here, maybe better from a distance point of view, but it's a little bit narrow. So those are just kind of my thoughts. When I look at here, the left, it's just as wide as the widened part of the middle, but now I'm closer. So I'm kind of leaning towards this, would you agree? Yeah. All right, so I'm going to do one more E-flow just to make sure that I'm not going to hit a vessel on the way to the vessel, and I'm good there. All right, so now we're going to use the 25-gauge portal pressure measurement device. It's the 25-gauge needle, like just similar to an FAA needle, will go down the inlet of the channel. I'm going to adjust my sheath just as if I'm preparing for an F&A. So I've got my sheath there. So the difference is this needle is specially tested and designed and approved for intravascular work. And so it is indicated for this purpose. And the needle is attached to a three-way system called a stopcock, and that's attached to a 90-centimeter long non-compressible tubing. The tubing is then attached to the device, which is the pressure gauge. And I don't know if you're seeing the pressure gauge image yet or not. We should have that for you shortly. So the pressure gauge is sitting on a table. I had the table leveled. There's your pressure gauge. It's sitting on a table. And I had the table leveled to the patient's right atrium, which is approximately the mid-clavicular line height-wise. So then that's the proper zeroing point for the pressure transducer. And so now I'm going to advance the needle into the vessel, and then I'm going to flush the needle. The needle is already primed with very dilute heparin saline. You can use saline by itself or dilute heparin saline. And once I'm in the vessel, I will just flush a few drops out to clear the needle tip, and then the pressure will rise, and then it'll equilibrate, and then I'll take a measurement. So I'm going to demonstrate that to you. So my needle is right there. So I'm just gonna adjust myself a little bit so my needle trajectory is going to hit the vessel. And then it's okay to go through and through these vessels because nothing will happen on the opposite side once the needle comes back. So I got my trajectory, I'm gonna go fast. So the needle went fast, it went through the vessel, through the outside wall, which is fine. And so now I can safely back up until the needle is in the vessel. And the nice thing about this backing up technique is as I'm pulling back in the needle, the vessel will actually get larger because I'm tugging on that front wall. So watch, I'm pulling, pulling. See how the vessel is actually getting larger, not smaller. If I go the other way with a front door approach, I will collapse the vessel a little bit before entering. So this is a nice way to get it right in the middle there. So I like my position and now we're gonna do the first flush. Okay, I saw some micro bubbles and now we're gonna wait for equilibration and Uzman will call out the numbers. 23, 22, 21, 20, 18, 17, 16, 17, 18, 17. 16. And Dr. Chang, do you always intubate your patients for this procedure? I do, I like to. It can be done on the mat, but I like them to be really still. 13. 12. 13. 12. 10. I know that this has to be repeated. Would you donate 30 seconds or a minute for Chaim to conclude? Sure, please. I'm gonna do two more measurements and then by the time you come back, I'll be in the portal vein. Okay, great. Oh, that was fast. Welcome back. So we did- I promise. Thank you for keeping your promise. I did five and so the last three in a row, I'm gonna have Uzman tell me what those three were again. Okay, so the measurements were seven millimeter mercury, six millimeter mercury, and eight millimeter mercury. Okay, seven, six, and eight. And even I can make an average of eight. Okay, so eight millimeter mercury, which is normal for the hepatic vein side. So now I'm gonna come out, I'm gonna turn on eFLOW and come out. And I don't see any flow in the needle track, typically we don't see any flow from a 25 gauge needle, but our platelet count is 87,000. So I just wanna be very careful and I don't see any flow. So I'm gonna come out and now I'm going to target the left portal vein. So I'm just gonna move my scope in a little bit and there's the left portal vein. How do I know that? Because it looks like it, but I can always double check with the eFLOW with the pulse wave. I'll invert the, we optimize this for Thomas, he'll appreciate it. And quickly tell the audience what you would do if you saw some flow in the needle tract as you're pulling out. Yeah, so for these small needles, the main thing is don't pull the needle out, just leave the needle in and that'll tampon out it. You can slowly back up and change the angle of your needle as it comes back, because blood is harder to make those corners. But if you're doing a liver biopsy, 19 gauge needle and there's flow, I did make a seven minute video on the US blood patch salvage technique. And if we have time, we'll show that to you. And hopefully I don't use it in this live case, but anyway, if you see flow and your needle is full of specimen, you can put your stylet back in, give back to the patient 25 to 50% of what's in the needle. You're just giving back the last portion of what came in the needle. And usually that's blood and that blood's already clotted because it's been in the needle. And so you give the patient's own blood back to plug up the hole. And then once you confirm there's no flow beyond your little barrier that you created, you can come out. So it's an excellent question, but a really important safety maneuver. It's an interesting hemostasis technique. Maybe you should consider where you could use otherwise. Ah, Thomas, you're still thinking. All right, so we've confirmed that that indeed is the left portal vein. So I'm going to optimize my distance this way. I think I like that distance. And so I'm going to aim my needle thusly. Oh, hold on right there, right there. And then I'm going to go, once I have a good position, I'm going to go quick. So that was quick and I'm in. So let's go ahead and flush. So do you see the level of today? 29, 27, 24, 23, 22, 23, 22, 23, 22. Okay, 22. So let's take another sample. So right now, assuming that's a good number, 22 minus seven is a gradient of 15. 26, 25, 23. So normal should be five or less. Five to 10 is portal hypertension. Greater than 10 is clinically significant portal hypertension. And greater than 12, high risk for bleeding from varices. 16. 16, okay. Take 16. 28. That's data from indirect portal pressure measurement, right? That's correct. We have to kind of, this will be the new standard, Thomas. So we'll have to create new numbers. 16. You want to repeat another value? Yeah. So we've got a little bit of divergence of numbers, 21, 16, 16. So we keep going until we get three numbers that are close together. 16. 16. What's the reason that it's dropping on? Yeah, sometimes you can have like a couple of air bubbles and that could influence the pressure. So each time we clear the bubbles and we get another measurement. So the last three in a row that were consistent were what, Usman? 16. 16, 16, 16? Yeah. Okay, so 16 minus seven is nine. So this is more consistent with her clinical picture, meaning she has portal hypertension. It's one point away from clinically significant. She doesn't have gashing or esophageal varices. And this is really the key. We can diagnose these patients who are not yet clinically manifesting, yet are on the way to portal hypertension decompensation. And we've had a number of these and Sai is really turned on by this. She's published some studies where you can drop their pressure from abnormal to normal after an endoscopic sleeve gastroplasty. They lose, you know, 20% of their total body weight. You come back in a year in a NASH patient, you measure their pressures and they normalize. And that means that we have a window of reversibility for these patients, which is tremendous. And before this technology, you couldn't even know that they were in that potential reversible window. You wouldn't even know to be so aggressive in managing their metabolic disease. So anyway, preaching over. I'm gonna take my needle out. All right, so taking my needle out, there's no flow. And do you do this one supine or left lateral, Dr. Shane? Yeah, so the patient is completely supine because we're trying to get to that right atrial level. And if they're up on their left side, I'm not sure where the heart is exactly. But when they're lying flat, and that's the standard for interventional radiology, they lie them flat. So that's what we did today. So in summary, we have an elevated gradient of nine millimeters of mercury. And so we need to do something. Now we need to find out what the etiology of our liver disease is. So I'm going to try to get some really good sampling. I'm likely going to sample both right and left lobe with liver biopsy. So maybe in the remaining two minutes, we can show you that or... I don't know if the other side is almost ready or we have the flexibility of a few more minutes. Dr. Chang, you can go ahead for a few more minutes. Thank you, thank you. So can any difference, this is Amit here. So any difference whether you do it under propofol versus general anesthesia? One of the attendees had that question. No, I would say all of these anesthetic agents can potentially drop your portal pressure, but it drops your portal pressure and your hepatic vein pressure at the same time. So the gradient is always consistent. So the interventional, the hepatologists, especially in Europe, really put a lot of value on the absolute number of the hepatic vein. And our absolute value today was seven, which is a little bit, maybe one or two millimeters higher than if you did it transjugularly. But the key thing is the gradient, right? The gradient is very, very accurate. And obviously if the hepatic vein pressure was 25 or 30, all then you were really suspicious of a right-sided heart failure. And so if you have an elevated hepatic vein pressure and a normal gradient, that's a right-sided heart failure to have proven otherwise. And then there's another question that where should we measure the shear wave elastography at 30 degree angle or in the center? Yeah, I would just go right underneath the transducer, almost like you're targeting for an FNA. But again, make sure that your transducer isn't even in the slightest way pushing up against the liver. Because even a slight push on the liver will make that liver more stiff. Thank you, Dr. Chang. We will wrap up the session one here. Thank you, UC Irvine team. Okay, thank you.

EUS-guided portal pressure measurement

shear wave elastography

liver biopsy

portal hypertension

spleen enlargement

fibrosis

liver disease etiology