It's my great pleasure and honor to welcome Dr. Ken Chang, you know, who is needs no introduction but for the sake of formality I do have to say that he is breaking away from another event and has joined us very graciously to deliver the state of the art lecture on endohepatology without which no US masterclass can be complete in 2023. Dr. Chang is chair of the section of GI at UC Irvine and also is the executive director of the HHL Digestive Disease Center and professor of medicine at UCI can welcome is my personal thanks to you for doing this and very grateful that you're here and made the time. Okay, so practical approach to us and endohepatology interventions. These are my disclosures. By way of outline, I just wanted to review the big picture of endohepatology and then dial and focus a little bit more on some of the unique features of endohepatology that's really catching on, one of which is US guided shear wave elastography, then you have liver biopsy for the practical aspects of it, liver biopsy has been around for a while, but what is the best technique? How do we get these beautiful long cores with 20 plus portal tracks, so I'll share at least my journey with liver biopsy and where we are, what the technique seems to work really well for us is. US portal pressure gradient measurement, everyone's heard of it, so I'm going to review some of the technique and also some of the newest data. Endohepatology, we coined this back, it's been 10, 11 years now, Vivek, and we thought that we would define endohepatology as the integration of endoscopy with the practice of hepatology and like endovariatrics, endohepatology seems to be catching on as a new growing field. One of the real advantages and attractiveness to this concept of endohepatology is that it represents a one-stop shop endoscopic liver evaluation and our hepatologists actually really love this service because a lot of unanswered questions can be addressed in one procedure. During that one procedure, certainly on endoscopy, we look for varices and portal hypertensive gastropathy, but then we just switch scopes and we go to EOS, we can examine the liver, we can image the liver, look at the liver edge, look for trace of sites, but then we can turn on shear wave elastography and as we'll show you, this is better than FibroScan in terms of a non-invasive way of looking at liver stiffness and the advantages, we can look at right lobe, we can look at left lobe, we can do spleen elastography, which is something that MR elastography can do, but the FibroScan technologies cannot. So we have a clear advantage in terms of bilobar assessment as well as spleen stiffness. If there's a lesion to be concerned about, now in the States, we can give Lumison, an FDA approved ultrasound contrast for evaluation of the liver and we can identify focal lesions that may otherwise not be clear on simple imaging. And then liver biopsy, we can get on the same procedure if indicated, and then direct measurement of the portal pressure, the gradient of the portal vein versus the hepatic vein can be obtained on the spot. So if you can imagine all of this done within, you know, 45 minutes procedure, answering a whole lot of questions, it's the power of this collective value, which is making endohepatology really attractive and catching on. So if we look at NAFLD, NASH, cirrhosis, or any liver disease and its progression, and ask our hepatology colleagues, what are your unmet needs? How can we as endoscopists help you in your practice? And the answer comes back as well. We don't always know if a patient has NAFLD versus NASH. And so oftentimes, non-invasive testing give us a sense for that, but really it's the biopsy that's definitive. And although the pendulum has swung and we've moved away from liver biopsy, liver biopsy is becoming a bad word these days. And that's because of the sampling is variable and patients can complain of pain and they're sitting in the recovery room for four to six hours. Now that we can do it with EOS, it's quicker, it's safer, patients tolerate it quite well. And so we're finding our hepatologists are asking for more liver biopsy than ever before. So EOS liver biopsy can really address the situation where you need a definitive histological diagnosis. The other unmet need is that slippery slope going from fibrosis to early cirrhosis to decompensated cirrhosis. And although we do have non-invasive testing, EOS shear wave also can be very helpful, especially when the fibroscan or the transient elastography is equivocal. And we have lots of experience with false positive and false negative transient elastography. USPBG becomes important if the question is, does the patient have portal hypertension? Yes, no. And what is the magnitude of the portal hypertension? Does the patient need intervention? Do we need to ban the varices for completion? Should we send the patient to TIPS? And what is the prognosis? So USPBG. And we talked about contrast EOS in cases where there's a focal lesion. So you can see that EOS can play a role in quite a bit of the spectrum of liver disease from diagnosis to staging. So I'm going to show this three minute video on EOS elastography. This is obviously imaging. And here there's a little box that will give us this region. And what happens is that the shear wave, which is the second ultrasound wave, it's a very forceful, powerful pulse wave that goes down. And when it does that, the algorithm can calculate the speed by which that wave is propagated through the liver and the faster the speed, the stiffer the liver. And that's the exact same concept as the transient elastography. Here we can see we took 10 passes on the measurements and the E value is the stiffness. And this is 11.4. The VSN is the level of confidence. It really 100% is the highest. And if you have total assessment of everything in the box, then you get a VSN of 100. So you want it to be at least 50 to give you an accurate number. VS is just the velocity. We don't really care too much about that. So the numbers that we look for is the E value and the VSN. So here the median E value is 11.4 and it's measured in kilopascal units. 11.4 is left lobe. So 11.4 in the left lobe, then we'll go to the right lobe. Okay, those are good numbers. And we see that the right lobe is 15.9. So it's not unusual to get slight variability between lobes. And we know that the lobes can have variability in fibrosis and hence stiffness. All right, so we have it. So then from here, we can also go to the spleen. And the beauty of spleen is that the shear wave of the spleen, when you do any shear wave of the liver, sometimes fat and inflammation can affect the stiffness. And that doesn't necessarily is directly related to fibrosis. But in the spleen, there's no inflammation, there's no fat. And when the spleen pressure or stiffness rises, that's a direct result of portal hypertension. So sometimes the spleen stiffness is actually more important than the liver stiffness. And here we're getting a value of 55, normal is about 25 or lower. So this shear wave of the spleen is turning out to be a very, very important part of the portal pressure assessment and looking at portal hypertension by imaging and looking at spleen. It is 55.3. So at this recent DDW, we looked at 44 patients who underwent simultaneous US shear wave and liver biopsy. And so we look at the correlation between the shear wave value of the left lobe and right lobe using a cutoff of 12.5 kilopascals. And if greater than 12.5, 88% of patients or 89% had F3, F4 on the metabiotic score on the liver biopsy. So it's a very, very high predictor of fibrosis by histology. We then looked at combining the shear wave of the liver with the shear wave of the spleen and combining these two characteristics, we were able to predict F3 or greater fibrosis with a positive predictive value of 80% and a negative predictive value of 93%. Now, moving on to liver biopsy, I did want to go over the technique so that people can understand the concept behind the technique. So here, obviously, we're finding an area of the liver that is most devoid of large vessels. And typically, it's the right lobe of the liver that gives us the biggest, longest space to do the liver biopsy. So typically, I'm in the duodenum, and I'm imaging relatively close to the gallbladder, segment 5, and you can see a wide open space that's devoid of vessel. So the technique that I'm going to show you in this video is using the 19-gauge Francine needle. The Francine needle, in my opinion, is the sharpest of all the needles in terms of precise cutting through normal liver parenchyma. This is not tumor, this is a liver that may be fibrotic and cirrhotic. And the three sharp points to the Francine needle, I think, is exquisite. So with this needle, the technique is I'd like to prime the needle with heparin. The heparin never enters the patient, it stays in the needle. And the purpose of the heparin is as you do your first actuation and the liver specimen comes into your needle, it prevents clotting, and then you can take a second or third actuation and move the specimen higher up into the needle. So what I typically like to do is get everything lined up. My first actuation is straight from the duodenum or from the stomach. And I don't pause, I just rapidly push the needle to the extent that I measure to be safe. So whether it's eight centimeters or six centimeters or four centimeters, I will measure the liver and put the safety lock. And then when I'm ready to throw, I throw the needle as fast as I can to gain speed. And speed is a factor for getting nice liver core. The second thing you'll notice on this is that I'm not putting a syringe on the needle. The needle is primed. My syringe is ready, it's a 20cc syringe, and I pull the stopcock back to 15, and I lock the stopcock. So the needle is ready, I mean the syringe is ready, but on the first actuation, I don't put it on and lock it to the handle. This is a lesson that I learned over time, is that if I were to put the syringe on the back and lock it, and I do my throw, essentially my front door is open but my back door is closed, and the specimen doesn't fly into the needle as well as if the front door was open and the back door was also open. So the first actuation, there's nothing on the back side. It's just the needle itself, no stylet, it's all primed with heparin, and I make my first throw. Then I'll show you what I do for the second and the third actuation. So that was my first, let me back it up a little bit. So that's my first actuation, very, very fast, and then here is where I put the syringe on and I turn on the suction just for two seconds and I turn it off. The two seconds of suction is just to get the specimen to ride into your needle a little bit. You don't want to keep the suction on because what will happen if you keep the suction on, that specimen will ride up the entire needle. It'll go up through the stopcock into the syringe, and in that process, your specimen will get mangled. You'd never want your specimen to shoot up into your syringe. So you turn the suction on, two seconds, shut it off, and that just pulls the specimen securely into the needle. Then for the next actuation, you want to back the needle up and stop about one centimeter-ish within the liver parenchyma. You don't want to take the needle out for your second actuation because then you're going to make another hole in the capsule and another hole in the capsule. The idea is to only violate the capsule once, but within that one pass, you can do multiple actuations. So here I'm going to do a second actuation, and now for my second actuation, because there's a specimen already in the needle, I'm going to turn the suction first and then throw the needle out. And the purpose of that is that suction will be on for the few seconds that the needle is traveling forward because as the needle is traveling forward, I want to create room in the needle by sucking the first specimen higher and allow the second specimen to come in. So it's a dynamic suction. I turn it on just before actuation, then I do the actuation, and then I stop the suction by turning the stopcock. So that's the second one. And now that I turn off the stopcock, and then I come back, and now I'm going to realign, find a slightly different trajectory, and when I'm ready to throw, I turn on suction, throw, turn off the suction, and then come back. So single pass, three actuations, and then I stop before taking the needle out, and I'm looking at flow in the needle track, and I don't want to take the needle out if there's flow in the needle track. Let me back that up. So I want to make sure that the flow stops before I take the needle out, and sometimes it's just simply waiting one minute, two minutes, three minutes, and eventually it will stop flowing. In the 10%, 5% cases where the flow doesn't stop despite three minutes, four minutes, then we apply this technique, which we published in Video GIE, called US delivery of blood patch. It's nature's gel foam. The concept there is this needle only has one lumen, and it's filled with your specimen. There's no room to inject gel foam, but you don't want to take your needle out because once you take your needle out, you'll never find your hole again. So while the needle is in, the only thing that you can do is push some of your specimen back out into the needle track, and that's simply taking the stylet, putting the stylet back in the needle, pushing it forward about 25%, give the patient back 25% of his or her liver. Actually, most of it is blood clot, and blood clots faster in the needle because the needle is cold, there's no flow, it doesn't have any push behind it, there's no pressure, and so the blood will clot faster in the needle than in the needle track. So you push your stylet in 25%, and that blood clot falls back and blocks the track, and almost always, as a matter of fact, in my case, every time it'll stop the flow, and then you can safely pull the needle out. So I'll just show you, this is our routine, this patient had cirrhosis, and this is the kind of specimen that we're getting fairly routinely. So this patient had stage four out of four cirrhosis. So I wanted to share with this, I wanted to slow down and share that with you because this is the technique that I think will really help a lot of us who get frustrated with fragmented liver. Okay, so I think I've burned all my time. Just a few words on portal pressure, and I'll skip through these slides, but the EOS PPG is becoming more and more important as we understand that direct measurement of both the hepatic vein and the portal vein can be complementary or better than trans-trigular HPPG. And so the technique involves putting the needle into one of the branches of the hepatic vein, and then typically it's the right portal vein. So I'll just show you, I'll end with this video. There's my needle. This is the 25 gauge needle, it's going in, so this is the IVC, this is the middle hepatic vein. The needle goes in. I'm going to come back just a little bit. And so the needle is already primed and we flush it a little bit and then we let it equilibrate and it's giving us 10 millimeters of mercury at the pressure. And then we flush the needle and repeat the measurement three times, and typically it'll be very, very precise like this. And then simply take the needle out and then identify the left portal vein, advance the needle into the portal vein, measure it three times, and then under Doppler, take the needle out. It's a very fast procedure and quite safe. And here the gradient is really the difference between the hepatic vein and the portal vein. So I won't go through this data, it should be available to you on the syllabus. And we've got a lot of emerging great correlative data on the impact that this can have for patients with cirrhosis. And what's interesting is that NASH cirrhosis seems to have a pre sinusoidal component. And so the patient with portal hypertension from NASH, it may not be all just be from fibrosis. It may be partly by the steatosis. And so patients can have varices and not have mature cirrhosis in NASH cirrhosis. And the transjugular measurement is less accurate in NASH cirrhosis as compared to, say, alcoholic cirrhosis or hep C. So we're finding that this technique, because it's simple, it's safe, and it's a direct measurement, has advantages as well as the accessibility of this technique for patients compared to our traditional IR approach. So with that, I will end and see if there's any questions. Thank you. Thanks, Ken, as always masterful and covered a lot of ground in a relatively short period of time, especially towards the end of the day. Thank you. There's a couple of questions here, when you do shear wave elastography, and thanks for showing that as well, because that is really the newest kid on the block. How do you decide, you know, which area of the liver to go and, you know, go measure these, do these measurements on and how do you select your target zone? Yeah, I like to go, I like to start actually with the right lobe, because in the duodenum, you advance the scope to the superior angle of the duodenum, and you rotate slightly, so you're almost turning towards the kidney, but not quite, and you're imaging segment five. Your scope is relatively relaxed, and your knobs are not cranked, and respiratory motion is not an issue from the duodenum, and everything is very stable, and your ultrasound transducer is not compressing up against the liver. That's the one thing that people don't, don't appreciate when they're starting, that any gentle push or pressure of the transducer up against the liver parenchyma will artificially increase the stiffness of the liver, which makes sense, right, if you take a sponge and you squish on it, it's going to be less elastic at that point, so the right lobe is the best place to get the most accurate, high DSN, really beautiful, you know, consistent numbers. So let's say you do that, and you get, you know, 13.2, whatever is the median, then I go to the left lobe, and I want to repeat it, but at least I have a ballpark of where the liver stiffness is going to be, because the left lobe is trickier. If you, if you go deep in the stomach, where the left portal vein is, and so on, the respiratory motion can make it almost impossible for you to get a nice run of measurements, because you're always fighting against the movement of the liver against your scope. If you go much more proximal towards the cardio of the stomach, things are actually more stable, it's counterintuitive, but you're actually more central near the diaphragmatic carotid as opposed to out peripherally, a little bit more stable there, and then, and then you take your shear wave at that point, knowing, now if you, if you get a value that's twice of what you got at the right lobe, it's probably wrong, and you're probably compressing it, so I try to keep relaxing it until I get a number, the highest number in the most relaxed position is, is what I, you know, will find a good number, and then you do 10 passes, and then I go to the spleen and measure the spleen stiffness. So that was interesting to see the splenic liver correlates, as you showed very elegantly. Thanks for explaining that. One of the questions folks have is, is the SWE built up in the new modules that are coming through, or do we have to order shear wave separately? Standard elastography is now built in, but maybe shear wave is not. Right. So in the Arriera processor, it's built in to all processors, so, and there's a button, SWE. Like you showed, yes. Yeah. So that's it. But in the F75s, no, it's not, it's not available, and in the older processors. Correct. Thank you. And I think another interesting question, when patients present with heart failure and you're doing PPG, how, are there any caveats that you would like to share, a good idea, not a good idea, you know, confounding variables? Yeah, no. So this, this is the post-hepatic portal hypertension. Correct. And in that situation, you'll, the gradient will not be widened, but your portal vein pressure will be high, but your hepatic vein pressure will also be high. So both will be high. So the hepatic vein pressure, instead of being, you know, between eight and 16, it'll be 25 or higher. And then your portal pressure will be, you know, three points higher than that. The gradient will be three. Both will be elevated, and that's a diagnostic for right-sided heart failure. Right. So you have to factor that in and, and be aware of that as well, I think is the point. In terms of, is there any particular benefit in, you know, portal waveforms and, you know, or we just go by numbers, like IR has waveforms, potentially GAT lab has waveforms. Where are we with waveforms vis-a-vis numbers? It's an interesting question. Yeah. So that's a very insightful question. So when IR does it, they look at the waveform and they do it at the bottom of the waveform during patient's inspiration. This device, this pressure transducer is actually calculating many more numbers than it's showing on the, on the display. And it's calculating it to two decimal points out, but then it's, it's giving you the next nearest whole number. So my, my version of the waveform is a lot of times when, when the number is stabilized and let's say it goes 12, 11, 12, 11, 12, 11, 12, 11, I'll just take 11. And that's kind of my bottom of the, of the wave. And I find that that's, that's a good consistent way of, of measuring. If it just gives you one number all the time, then fine, that's your number. But if it oscillates between two numbers, take the lower number. And as you've shown, and we've seen as well, is that when you look at the portal and the hepatic venous systems, the waveforms are quite dramatically different. And I think early on in the process, along with the anatomical correlates, the waveforms are very useful and almost mandatory to be part of the initial diagnostic evaluation of where you need. Yeah. So the way, sorry, I thought that you were talking about the waveform, the pressure waveform that the pressure waveform that the Right. They were referring to that as well. Yes. Okay. And then the, the, the ultrasound waveform. Yes, for sure. If you're ever confused. Is this hepatic vein is this right. Then the post the waveform there can really separate because they're totally different portal vein is a whole systolic diastolic venous home, and the other is four phases ASVD. It's like completely different. Right. And I think you mentioned this but for all the end of hepatology interventions including PPG, is there anything in the recovery room that you do different pain wise any, anything that you've seen that is unique. Any other patient hemodynamic behave anything that students would take away should be important in the recovery room after these interventions. Yeah, so after PPG, nothing because, you know, it's a tiny needle, and so I've never had a patient complain of pain from that. But for your 19 gauge liver biopsy, you went both low, you know, you got 20 centimeters of liver, you, you can't, you can't have pain. Typically, it's not a hematoma which is what we would experience with a blind percutaneous biopsy, but their pain I think is the needle going through the stomach. So, you know, these patients will watch them longer here and there, you know, we've admitted one or two patients, even gotten a CAT scan. There's nothing there, and the pain just resolved. But you can't, you can't assume you have to assume something, you have to assume it's a bleed. Correct. Like with anything new. I remember when we were doing and aluminum ablations, we had a low threshold of overnight monitoring so I think it's prudent to keep them and watch and assume the worst and then as time goes on you will get more experience. One question is that do you biopsy both lobes of the liver each time. Given the. You do. Okay. Yeah. So, so I will routinely biopsy both sides, especially, you know, in patients with like hep C where you can get quite a bit of variability in terms of degree of inflammation and fibrosis in each low. So typically I'll do right low first. And that's where I get my longest beautiful for, and then I'll go to left low, and my core will be maybe slightly less but I'll have sample both sides. The caveat is, like, yesterday, two days ago during our symposium, there was a patient who split the count was 61,000, and had clear four out of four cirrhosis and huge gastric varices. So, I did my right low got nice specimen, and then got out of Dodge, because at that point, it wasn't a question of severity of fibrosis we already had a photo gradient of 12. They just wanted to know, is there Nash, on top of hep C or just hep C. And so I gave him nice core from the right low and again individualizing it as you guys have been talking about, I didn't, I didn't do the left low because why. Yeah, right, right, right. Appreciate. I think one of the questions came up is, is it necessary to do the, the, the manufacturers training session or can someone just send you a first class ticket and, and, and be done with the training part so I always say this jokingly but you know, in the beginning it was kind of only available that way but I suspect now with proctorships and other avenues we can learn this, you know, with the different venues right. So you're talking about the PPG right the PPG I believe yes, that's the uppermost in folks mind. Yeah. Yeah. So, until now, it has been a requirement by the company before they'll sell to you to attend one of the courses. But like you said, you know, you you were the early adopter, and we, you know, there should be a way of not having to centralize the training, but to decentralize right question is for the company's point of view, how do they, how do they call it quality control, especially in the early launch, they just don't want to have someone misuse it and get a bad complication and then shut the whole thing down. Absolutely. No, thank you. Listen, you know, it's 415 we had promised folks. This was a will start winding down right now now Girish welcome back if any of the other faculty are still available or definitely welcome them back I know not the least. And just one question. Yes. Yes, go ahead. Great seeing you. Thanks for your great talk, always learn from you. Can you just have you had a pretty significant post liver biopsy bleed and if you have, why do you think it happened and then how did you treat it. So knock on wood I've done over 300 of these and I've not had a bad lead. But my colleague had one really badly. And it happened. The next day, the patient went back on anticoagulation too soon, and had a massive leading had to come back in. So, it can happen. The immediate lead. I would say if you follow that technique of watching for flow in the needle track and wait until there's no flow in the needle track and carefully take the needle out under direct ultrasound and, and, and looking at the Doppler. And then after you take the needle out, still continue Doppler in for a few more minutes to make sure there's nothing coming out of the needle track and swirling outside the liver capsule, expanding the space between the liver and the stomach or the duodenum. If you take all of those precautions essentially there was no lead. Right, and you don't have to worry that in recovery. They're still bleeding because they weren't bleeding when you finish the procedure. Now, a delayed lead is is another story and that's you know that one patient who went back on, but then it was too soon. So I do caution patients about the late leading. But, yeah, I think, you know, and I have, you know, around the globe I collect stories about fatal bleeds right from liver biopsy and they're there. They're definitely there and you know some of these needles for example, the three problems of the Francine needle if this is a vessel. If I go like this. It's going to cut that vessel in two places, it's going to actually like chunk out the vessel. And that's an unforgiving, you know, bleed right it's not like the other simple needles, you know, it'll glance it and maybe slice the vessel in one place partially, and that may cut off. But this will not, this will not easily cut off right it's it's cutting it in two places. So these leads can be significant. And, but if you follow those steps, and you use the blood patch as a salvage. I think it will make this extremely extremely safe. And my sense is that people are just doing biopsies with the same technique as say a pancreatic FNA, and not and and and that's where and they're under reporting or, you know, I mean, you read the data and the literature, I think in my experience it's a lot like what the micro forceps with pancreatic cysts you hear all the great results, but all the other downside and complications people don't mention and I think, you know, we have to tell folks that yeah it's a great technique but it has to be done the right way you can't just, just because you know how to do FNA and FNB doesn't mean you should use that for liver biopsy. Couldn't agree with you more. It's, it's a completely different mindset. And also, as we discussed very early on is almost seems like days ago right when we compared FNA versus FNB technique already there is a difference in the approach to the lesion. But this is fantastic. Just want to be respectful of time real quick here. And I think we've answered all the questions. Anticoagulation after liver biopsy. Can we, is it any different than after an EMR in the colon? Similar. Similar, very similar.

endohepatology

US-guided shear wave elastography

liver biopsy techniques

portal pressure gradient measurement

varices assessment

NAFLD diagnosis

portal hypertension evaluation