Good afternoon, everyone, and welcome to the ASLD webinar entitled Applications of Tips for Portal Hypertension, Entering a New Era, brought to you by the Portal Hypertension SIG. My name is Elizabeth Verna. I'm from Columbia University in New York, and I'm honored to be moderating this webinar. Next slide. I'd like to introduce our distinguished speakers we have for you today. This is Dr. Virginia Hernandez-Reya, who's an interventional hepatologist from the hospital clinic in Barcelona. Next slide. And then we have Riyad Salem, who's the chief of interventional radiology and a professor of radiology at Northwestern University. Next slide. This is our agenda for the webinar today. We're going to start with Dr. Hernandez-Reya talking about indications for tips, the old and the new. Where do we go from here? And then Dr. Salem will discuss tips for portal and mesenteric thrombosis and serotics and non-serotics. This is going to be followed by a 15-minute live Q&A, and I would like to remind everybody to please put any and all of your questions into the Q&A section of the Zoom and not into the chat, and we will do our best to answer everybody's questions either in a written form or live at the conclusion of the webinar. Next slide. Thank you very much, Dr. Werner, for the nice introduction, and thank you very much to the ASLD and the SIG for choosing this nice topic for this afternoon. So before starting speaking about the indications for tips, I want to show you how standard tips looks like to compare with the images that Dr. Salem will share with us later in the afternoon. So a tip is the connection between the portal vein and the hepatic vein, and the important thing here is to place the tips that most of the time nowadays we place cover stents to place the uncovered part in the portal vein, but the cover stent has to start in the confluence in the entrance of the portal vein into the liver and then covering everything until the confluence of the hepatic vein into the inferior vena cava, and this is how we do the procedure. We catheterize the hepatic vein with the needle. We puncture from here the portal vein. We connect the two veins, and this is how we see the notch where the portal vein becomes extra hepatic, and this is the other notch, and we cover everything with the stent as you can see here. So if we start with the indication, the classical one is ascites, and research in the last years have moved a little bit the indication from refractory to recurrent ascites. We all know that patients with refractory ascites, they do very bad. They had a bad prognosis, and we should always consider liver transplantation. However, not always it's possible. Some patients have contraindications, and the waiting list can be too long, and here is where TIPS has a role. In this table, you can see all the studies that we have, the randomized clinical studies evaluating the impact of TIPS in refractory ascites, and in almost all of them, but not in the first one that was all the study with small sample size and with a very high mortality in the TIPS group probably due to learning curve, but if we do not take into account this one, the TIPS was beneficial in all the randomized clinical trials, and the survival was either better in the TIPS group or neutral. But I want you to realize that all the studies that we have in this setting were performed with their stents and not with covered stents. And this is the individual data meta-analysis of these four randomized clinical trials where we can see how the impact on survival in these patients is much better in patients with TIPS, and this is the case in all the patients if we stratify according to the MELD, so patients with high MELD and patients with low MELD, they all benefit from a treatment with TIPS. But then in the last year, the question came in different ways, like maybe TIPS may have a more beneficial impact if we use the TIPS earlier, because we all know that patients with refractory ascites, most of the time when they arrive to the moment of the TIPS, they are sarcopenic, very fragile, and they have other comorbidities. So in France, they launched this randomized clinical trial in patients with recurrent ascites, and they randomized patients to cover TIPS versus paracentesis plus albumin, and they performed that in four centers. And the definition for recurrent ascites was this patient needing at least two large-volume paracentesis within a minimum interval of three weeks, but less than six in three months, so very early when the patients start developing ascites, that it's not treatable with diuretics. In all of the patients, they use cover stent, and they have a target PPG reduction of 12 millimeters of mercury. And the first thing is not all the patients coming to our outpatient or to our hospitals with ascites may fulfill this criteria, because this is a very selective group of patients with early diagnosis of refractory ascites. And if you see here in this table coming from the paper, less than 50% of the patient, of the total patients with refractory ascites met the criteria. But when we carefully select this kind of patients, we can really improve survival in this group of patients, and it's very deep in this setting. It's very good in preventing or in controlling ascites. And there were no differences in the development of hepatic encephalopathy in this trial. So this is the only randomized clinical trial that we have so far. We do not have other studies, but we have some data coming from retrospective observational studies like this one performed in Germany, where the authors, they analyze patients treated with TIBS, and they compare patients in whom the ascites was controlled versus those patients with persisting ascites after the TIBS, which is associated with decreased survival probability. And they could find the multivariate analysis that the frequency of paracentesis pre-TIBS was associated with a much better control of the ascites. So it seems that this strategy, it's better than waiting too much and place the TIBS when it's probably too late and the patient is sicker. But it's cost effective, this intervention in patients with recuvering ascites, and the answer is yes, we have this cost effectiveness analysis in which we can see how this is also a strategy that may save money to our health care system. The classical, another classical indication, it's bleeding. And also here, things have been changing in the last year, and we've moved from the rescue indication, which is an advanced, let's say, indication to a pre-emptive indication. And if we, this is a snapshot of all the stages in the patients with acute palatial bleeding, there is no indication for TIBS in primary prophylaxis. But also remember that the patient may have recurrent ascites, and you may go for TIBS, and then this patient would be also protective for palatial bleeding, and you don't need other prophylaxis in this setting. Then we have the rescue TIBS, that is the TIBS that we place in a patient who is actively bleeding, and what we want is to prevent, to control this bleeding, either at the acute bleeding episode, or as a prevention of re-bleeding in a patient that despite adequate prophylaxis is bleeding, and bleeding again during the follow-up. And this is a different concept than the pre-emptive TIBS, because in the pre-emptive TIBS, what we want is to identify the patients at risk of having a failure, and then treating them with a TIBS before failure arises. So the research in the rescue TIBS setting in the last year has been centred in identifying those patients that may benefit from this strategy, but also to define the patients in whom this strategy may be futile, because we all know that the rescue TIBS is associated with high mortality, it's something that is very effective in preventing bleeding, but most of the time the patient with failure is a very sick one, with liver failure, with other complications, and the mortality in this setting is very high. And this is a recent study coming from the UK, in all the patients coming with indication of rescue TIBS, and they could identify how patients with ACLF, the presence of ACLF on the top of the bleeding is associated with a decrease in mortality, and how the TIBS, in patients with ACLF, may be a strategy able to improve survival in this population. Probably not all ACLF patients, because this is another study coming from France, with a study cohort in several centres of France, and a validation cohort in Spain, and in this study, ACLF 3B grade was associated with a futile prognosis in those patients treated with salvage TIBS, and indeed, the authors, they identify these risk factors that were lactate and male, to predict the mortality in patients with rescue TIBS, and they, what they identified is that patients with lactate levels of equal or more than 12, or male, equal or more than 30, they have a very, very high mortality, and in this population, the rescue TIBS may be futile. But if we are not in the setting of the rescue TIBS, we have a patient with a racial bleeding, we do everything possible, we control the bleeding, even if we do everything following the guidelines, we know that up to 20% of the patients, they will experience failure during the admission, and then they will, we will go for a rescue TIBS in a patient that is, let's say, sicker than at admission, and this is the whole concept of pre-emptive TIBS. Pre-emptive TIBS, what aims is to prevent this failure to occur by selecting all these, all the patients that are very high risk of presenting failure, and treating them earlier, early with a TIBS. And why it's so important to do the TIBS early, and this is why initially it was called early TIBS, defining early as the first 72 hours, this is because if we take a look at what is the natural history, or the natural cause of the variceal bleeding hemorrhage, we see how the bleeding rates, the failure, and the death, it's concentrated at the very beginning of the initial episode. So if we want to prevent this from happening, we should place the TIBS as early as possible, and if possible, in the first 20, 24 hours. This is a table summarising all the studies that we have in the pre-emptive TIBS setting, we have studies coming from the east, from the west, randomized clinical trial and observational studies. The first one, the first study suggesting the treatment with pre-emptive TIBS used hemodynamic criteria to define the high risk, and then the different studies used the high risk criteria identified in the New England trial, that were child C less than 14 point, and child B with active bleeding at the initial endoscopy, despite active treatment with vasoactive drugs, and this was the definition of the high risk, and then in the lower part of the table, we have the studies coming from China, and the Scottish trial, and in these studies, authors define risk in a different way, and they use the TIBS also in child A patients, and in child B with and without active bleeding. It's very important to define the population, and if we take a look at the largest observational study coming from China, and treating patients, child A, child B, and child C, we can see how the child A patients, they do not benefit in terms of survival of treatment with TIBS, while the child C patient is the class where the benefit concentrates, and if we take a look at the child B patients, this is different in the B without active bleeding, and in the B with active bleeding, and seems that it's only in this population of patients where active, where preemptive TIBS may have a beneficial role. We have been debating a lot in the last years about this subgroup of patients with child B with active bleeding, and trying to identify or trying to demonstrate whether these patients are really at high risk of bleeding, and this was the aim of this meta-analysis of individual patient data, evaluating all the randomized and observational studies that we had at the moment, but only using the data of those patients with the traditional high-risk criteria, meaning child B with active bleeding, and child C less than 14 points, and HPTG equal or more than 20 millimetres of mercury, and in the study, more than 13 patients were evaluated, and more than 300 patients with preemptive TIBS, and this is the main results of the study, in which, which was the confirmation that selecting high-risk patients with these criteria, select a population that are at a high risk of bleeding, and you can improve survival in this population in the two subgroups, in the child C and the child B with active bleeding, placing a TIBS. However, if you look at the Kaplan-Meier curves, then you will see how the benefit is higher in the child C population, and then we wanted to confirm what happened really in the child B population, and if there is a subgroup of patients that do not benefit, and when we stratify the data according to the number of points, then we could detect that those patients with child B, but only seven points, they do not benefit in terms of survival. Of course, they do in terms of where bleeding TIBS is very, a very good treatment to prevent the bleeding, but not including survival. It's only the benefit in survival concentrates in those patients with more than seven points, and based on all these data that I have presented you, the last VADENO7 consensus recommended the use of preemptive TIBS with coverage 10s very early in patients with varicial bleeding and these high risk criteria that I told you, the child C and the B more than seven points or the hemodynamic criteria. We have also been expanding the indications, but also reducing the contraindications for TIBS, and those are data coming from the European cohort of patients treated with preemptive TIBS, the observational study, and also the meta-analysis. Here you can see how patients with fulfilling the criteria for preemptive TIBS, but with high levels of bilirubin, they also benefit from TIBS, same thing with patients fulfilling the criteria and with ACLF at admission, TIBS is also beneficial in this group of population, and in those patients with hepatic encephalopathy at admission, also the preemptive TIBS can improve survival without increasing the rate of hepatic encephalopathy after the admission for the varicial bleeding. And what are the non-classical indications that we have for TIBS? We use TIBS in vascular liver diseases to treat severe portal hypertension, and we can use with this indication in the portal sinusoidal vascular disorders, or in the previously called non-cirrhotic portal hypertension, these patients, when they develop severe portal hypertension, they can be treated with TIBS, and they do well with this treatment, in the indication of ascites and hemorrhage, and also the butchery patients, when we treat butchery patients with the stepwise recommended management, meaning that the TIBS will come in place when the patient progresses, when the disease progresses, despite anticoagulation or pericutaneous treatment, placing tips in this group of patients also improve survival. And my last, or the last indication that I want to comment is the preoperative setting. We know that patients with portal hypertension and HPPE more than 10 millimeters of mercury, they have, they may decompensate when submitted to a resection, hepatic resection of hepatocellular carcinoma. And the same thing happens when they undergo elective extrahepatic surgery. Indeed, in this study, evaluating the risk of the patients undergoing elective extrahepatic surgery and stratifying patients according to the HPPE threshold. In this study, we could identify how HPPE more than 16 define a population with a high risk of mortality undergoing surgery. And then the question here is, can we prevent this bad outcome treating patients with tips? And we do not have randomized clinical studies yet. Everything that we have comes from description of cases, proving that tips in the pre-op setting is safe and three retrospective studies. The first one, a little bit old from 2006, shows no differences in mortality. The largest one coming from France, also no differences in mortality. And the more recent one coming from Germany, evaluating 45 versus 45 patients with or not with tips. It seems that tips had a beneficial effect in this population. However, I think that we need prospective studies with high risk and much controls before we can really recommend the tips in the pre-operative tips in patients undergoing surgery. So thank you very much. And I want to finish thanking you all for being here in the webinar, but also my multidisciplinary team in Barcelona who made possible that we can do the tips placement and all the studies. Thank you very much. And now we can follow with the next presentation and it's Dr. Salem next. Thanks, Virginia. Thanks for the opportunity to present at this webinar, talking about the use of advanced tips techniques in portal and mesenteric thrombosis in both serotics and non-serotics. I have no disclosures. So I want to start with talking about patients that are serotics and basically, those patients that we deem probably will need a liver transplant at some point. We know that PBT is part of the natural history of patients with cirrhosis, up to a quarter of the patients will develop that. That's why we monitor them and make sure that these vessels remain patent before they go to surgery. We use the URDEL classification to look at patients with PBT. And one thing I just want to talk about very briefly is one of the limitations of the URDEL classification, grade two, including 50 to 100%. So partial and complete occlusion is effectively the same. So it's hard to really weed out some of these studies that only talk about grade two URDEL PBT. And in many of the cases that I'll be showing, it's effectively 100%. As an example here, this person on the left-hand side has a small sort of some millimeter flow in the portal vein. That's a URDEL grade two. And this one has complete cavernous transformation. That also is a URDEL grade two, but they're distinctly different entities. We also know that patients who have PBT do worse at liver transplantation. Really the idea initially presented by the Miami group is that at transplant, ideally you'd want to perform an end-to-end inline physiologic anastomosis for physiologic flow. And if you're unable to do that and insert, for example, shunts or grafts, the outcomes are worse. So the work that we've done here is based on trying to improve that and to minimize the morbidity and mortality of transplanting patients with PBT. And we know that at surgery, they are not insignificant. So the idea here is to improve patient outcomes that have chronic cavernous transformation and chronic PBT pre-transplantation. So you saw Virginia show some cases and on the right-hand side here is what sort of a normal tips would look like with veins that are open. But the idea here is at surgery for liver transplantation, would you rather sort of dissect down on something like this on the left-hand side or something like this on the right-hand side or something with cavernoma on the left-hand side here? So I think the answer is obvious that it's much more complicated to dissect through this. And we'll talk about how to simplify that for the transplantation. The study that we published years ago was a 61 patient analysis, looking at these patients prior to liver transplantation. And we have long-term follow-up on them. And just to further reinforce that what we are talking about today is not acute PBT. This tends to happen mostly in the non-serotics with expanse-style portal vein. This is chronic cavernoma here. No portal vein, small shrunken livers with ascites. So real cavernoma. The baseline characteristics of the patients are what you would expect in a serotic patient population, C, alcohol, cryptogenic, et cetera, with various manifestations of cirrhosis, variceal bleeding, ascites, encephalopathy. And here are the baseline melds. And of note, 20% of the patients had a baseline meld of over 18. Now, just for clarification, all of these patients were evaluated and prepped for transplantation in the case of decompensation prior to portal vein recanalization tips. Few of these patients have thrombotic disorders. There's a lot of thrombosis here, and 80% are uradelic classification grade two. And about 30% of them have involvement of the superior mesenteric vein and the splenic vein. I want to share some cases and show sort of the technical aspects of this, because I know a lot of people ask about this. So this is a serotic liver with ascites, as you can see, with a meld of 18. As you zoom in here, you see that there is cavernoma. There is no main portal vein. And upon a detailed review of the scan, you see that there is a straight splenic vein with an inline branch inside the parenchyma that is now amenable to direct puncture of the splenic vein and directly help with a recanalization. I start all of my tips with a wedge venogram. This is very dilute contrast wedge venography that shows me the right portal vein, the left portal vein, and no main portal vein. What we are circling here is the cavernoma. And notice how the cavernoma always bypasses the chronic PVT and maintains perfusion. It comes back into flow in the left and main portal vein. That's why in most cases of PVT, the intraparenchymal portal vein branches are patent because the cavernoma maintains their patency. We use ultrasound guidance to get into that splenic branch that I showed you. So this is a needle getting into that splenic vein. And we advance a very small system 5 French. And here we are performing a venogram, and you can see that the IMV is open. The SMV is open, but there is no main portal vein. There should be something here. There's nothing there. It is chronically occluded. The technique we use is a simple glide wire and a catheter to recanalize through the occluded vein. So this is the thrombosed vein that you can see here. This is the right and left portal veins. And so we have recatalyzed and advanced our system through here. And even just to further clarify, re-injected the system. So here again, this is a sheath inside the thrombosed portal vein. And this is the cavernoma going around and perfusing, as I mentioned, and maintaining patency and perfusion of the right and left portal veins. The technique is simple. We advance a snare into the right-hand portal vein. We puncture, we pull our system down, and we place a TIPS. Now, from a technical standpoint, the TIPS here has to be relatively short on the portal venous side. And that's because we want to maintain a good distance here for the surgeon to perform an end-to-end anastomosis. So here you can see the TIPS is in place. We're injecting contrast to show that, again, everything is still occluded. And this is an angioplasty balloon. And we dilate the system to 10 or 12 millimeters. And this is what it looks like immediately after. Many of these veins are just scarred and hypoperfused. And when you place a TIPS and reestablish flow, they are open. So you start from this with no portal vein to this. And now this permits an end-to-end anastomosis for the surgeon. We close the splenic puncture with some coils. And this is our completion image. So in this same patient that I showed you before, fibrotic, cirrhotic liver with ascites and cavernoma, and underwent a liver transplant and end-to-end anastomosis, everything is patent. So to continue, when we do this technique in this patient population, we started with, we not infrequently use the splenic access and in fact, also the hepatic access. I'll highlight that later on in the non-cirrhotic patient population. It's not uncommon at the end of the TIPS procedure to see some mild thrombus in the main portal vein. You do not chase that because at one month follow-up venography, that will lyse. The flow will lyse that remaining clot. And the adverse event here is acceptable with no major hemoperitoneums and the usual side effects that you might see from a TIPS placement. Portal vein patency in this patient population, extremely high. So very surprising that it chronically occluded portal vein when TIPSed and recanalized in the cirrhotic will stay patent. At the time of our 61 patients, we had transplanted 24 of them and 23 had undergone the end-to-end anastomosis, which was the initial intent without a patient developing a recurrent PBT or stenosis. So again, going back to this other case that I showed you, this is a small portal vein, but then we TIPSed this patient and I think this is a much simpler surgery, transplantation surgery, than trying to either put in a graft or trying to thrombectomize a patient with a large cavernoma and effectively no main portal vein. We just published this paper a few weeks ago because we wanted to show the long-term outcomes after transplantation. So we had now 35 patients. I just showed you before we were at patient 24. Now this is 35 patients that we have transplanted and we compared them to sort of an internal control of patients with minimal PBT that underwent straight transplantation without a portal vein reconstruction because those could be thrombectomized in the operating room. We achieved inline flow in everybody. The end-to-end was in 32 of 35, which essentially is very high success for the end-to-end anastomosis. Here are basically the baseline characteristics of what effectively is a high-risk group. These patients had chronic obliterative portal vein with cavernoma, 35, and these patients here, 14, had partial occlusion of the portal vein that underwent liver transplantation without the TIPS. And it basically shows that they are comparable with the exception of the degree of portal vein, of course, portal vein thrombosis, of course, much more in the group that required a PBR TIPS compared to those that went to the operating room. There is, of course, a level of decompensation that occurs in this patient population when you TIPS them. So we had more patients decompensated from B to C as you might expect. But again, all of these patients were prepped and ready to go to the operating room in case of a decompensation. Adverse events are effectively parallel what we reported in our first manuscript. So nothing significantly different and no major bleeds. In the operating room, this is what this table is meant to show, that effectively you have a high-risk group that was recanalized and opened for the OR, and in fact contraindicated, I think, for transplant in many centers because of chronic cavernoma and are now comparable to a low-risk group with partial portal vein thrombosis. The overall survival is effectively the same. If you look at this, we have, of course, much longer follow-up in the non-PBR TIPS group because these were done much about 15, 20 years ago, and then we adopted the PBR TIPS approach about 12 years ago. So the follow-up is a little bit different, but certainly the overall survival is no different. And again, we've converted a group of patients that are high-risk and I think contraindicated in many centers to parallel those that did not require TIPS. What does that look like? This is a coronal MRI scan. You can see the expansile portal vein thrombus that did not require a TIPS because this could be thrombectomized in the operating room. So we don't do PBR TIPS on everybody, but someone like this where you see no main portal vein and nothing but cavernoma, and here's the equivalent venogram. You see no main portal vein. This is all cavernoma. And again, notice that it bypasses the main portal vein to the right and left branches. This person would have undergone a portal vein recanalization TIPS. So for this case that I've shown a few times now, chronic cavernoma, no main portal vein, looks like this at the end of the procedure. Main portal vein is now patent. The cavernoma is decompressed. You see some peripheral portal venous flow, but I think certainly simplifying the operation. Let's now move and talk about non-serotic patient population. We started doing these given the success we had in the serotics, which were quite challenging, but we perfected our technique and now have been applying this approach in patients that are non-serotic. And so this is often termed EHPVO, extra hepatic portal vein occlusion. One to 2% of the patient population may have that, but we are certainly seeing a lot of patients that have had a history of either umbilical vein catheterization, hypercoatomal conditions, of course, and gastric surgery. We are seeing not an insignificant number of these patients have complete portal vein occlusion with significant cavernoma in this patient population. So if you look at this case, for example, this is a non-serotic patient with massive varices with cavernoma. So how do you TIPS this kind of patient? And this is the equivalent CT scan on this patient. You can see here, sorry, the MRI scan, you can see is a cavernoma. There's no main portal vein and these are all occluded venous system as well. And so how do you TIPS this patient? And so we reported this in an early series several years ago. And what we discovered was the addition of the hepatic access with the splenic access is what converted us to become much more successful in this patient population. So I'll describe that in a second, but effectively it is now the same thing where you have your snare, you puncture your snare, you have through and through access, and then you're able to TIPS the patient. So you go from something that looks like this that is effectively un-TIPSable without using some of these techniques to a decompressed condition that we have here. We published our data and this is certainly a group effort with our hepatology team here locally at Northwestern, but we just published our data a few months ago in hepatology. We had 39 patients of non-serotic and notice the etiologies here are distinctly different, hypercoagulable conditions, idiopathic, all of them had cavernoma and a quarter of them were post-operative. So again, we're seeing a lot of these. Notice the significantly more advanced degree of thrombosis. Three quarters of these patients had splenic vein and or superior mesenteric vein thrombosis. Manifestations of poor hypertension, pain, variceal bleed, some ascites, one cholangiopathy that I'll discuss a little bit later on, but notice here that the technical aspects are much more complicated and often require splenic and often transhepatic access, and I'll show you that in a few minutes, and very reasonable fluoroscopy times and radiation doses. Adverse events here, exactly what you would expect, major encephalopathy, not something that we see frequently in the non-serotics. So not a major limitation of the technique. Here's an example of somebody with a complete, this is sort of a patent SMV and IMV branches, but complete occlusion up more centrally. And this is what you have here. We have splenic access and hepatic access. So you convert this complex web of veins and portal hypertension with this tips here and completely decompress that system. Similarly here, we have splenic access. Notice the complexity of this thrombosis, much more complex than in the serotics with esophageal and gastric varices. And again, when you augment with the transhepatic access, now everything can be connected. And here we have the spleen, the occluded portal vein, and we are able to connect everything and now look like this. So we start from this to something like this using these advanced techniques. We've also augmented our approach and now sometimes puncture the SMV directly to recanalize up because that is the trick that we need. And sometimes even the IMV using fluoroscopy and ultrasound. So we use these techniques. The non-serotic patient population, portal vein recanalization tips, and this is afflicted with not an insignificant amount of very early thromboses because of the degree of thrombosis. But then we bring these patients back with more aggressive anticoagulation and secondary patency is much improved. So this is certainly a technique that requires secondary intervention to achieve overall optimized patency. Here's a case that we just did a few days ago. And I just want to show you what it looks like live. This is someone with a non-serotic, but this is what the portal vein cord often looks like in this patient or can look like in this patient population. So your job is to chase that, to identify that. And to chase that, you can see where it is here. You advance a glide wire because you can see it that under fluoroscopic technique. You advance your wire and your system. This is the intrahepatic portal venous system. As I mentioned before, here is your snare. You puncture your snare and you pull through and through and accelerate this video here. People have asked me how you do this. And you just basically pull an exchange length, stiff glide wire. So you now have through and through access through the thrombosis system. And you have a very stable access to place angioplasty balloons or stents. And then at the end, you are left with this. So you've now tips the very complex patient and decompressed their portal hypertension. I'll talk very quickly about two quick cases. One patient from Atlanta that we did several years ago, recurrent upper GI bleeding, negative workup, no identified reason for PBT. You can see here that he has cavernoma. And notice here that we are injecting, but I want to share with you sort of the complex nature of this type of patient population, the non-cirrhotic, you sometimes may not see a portal vein cord. And in this case, you see nothing but a tangle of vessels. And notice here that this is a cavernoma and a cavernoma in the main portal vein should be here somewhere, but there's no way to see it in this case. And that's why you solve that problem by puncturing the parenchymal portal venous system. You then identify the peripheral portal venous system and notice again that it is patent because the cavernoma maintains intraparenchymal patency. I have this catheter in the splenic system and it gives me a guide as to where to go. This is what we've done and now we've merged. So I'm now in the splenic vein. I will now pull myself up into that territory and puncture and pull my way through and now place my sheath. Notice again, these two cavernomas I showed you before, this is the main portal vein. So again, no way to ever get through that on the splenic side. You have to augment with a hepatic access in order to merge the two techniques. And here we are. And this is now a plate tips that has placed a decompressed all the cavernoma. And now there is outflow. And the last quick case I want to show is a 40 year old patient from California failed attempt at an outside center sleeve gastrectomy historically, and then develop a portal cholangiopathy sepsis and frequent stent changes. We wrote this up a few years ago. Here's the stent, but I want to show you sort of what that looks like. So this is a very complex splenic vein thrombosis. We access that side. Notice again, that stent is here and you can see that this cavernoma is compressing the biliary tree. So again, we augment our technique by puncturing the portal vein and now drilling to here. We now know where we need to go. So now we connect these two and we then snare each other. And now, as I mentioned, I pull my splenic side up into the thrombosed portal venous system. So I'm now in the normal channel. I pull my way through and now here's my snare. And again, notice that the peripheral portal vein is open because the cavernoma maintains patency. You puncture, you pull your way through and you dilate sometimes, and then you tips. And that's what we have done in this patient. So to conclude in the cirrhotic patient population, we know that PBT is associated with worse outcomes. And one of the considerations is to perform end-to-end surgical anastomosis. We found very good success recatalysing these patients. And certainly this has become our institutional gold standard to do this in the cirrhotic patient population. In the non-cirrhotics, you often need splenic and hepatic access. And interestingly, is being seen with patients with prior gastric surgery. They all have cavernoma and there are some technical issues that I can answer if there's some interest, but essentially the SMB is already occluded. You do not need to reopen it because the flow will bypass to the splenic hilum and be decompressed. So you don't need to sort of place kissing type stents. We do not do that. Encephalopathy is not a major issue in non-cirrhotics. I do think this is an unmet need and something that we need to study further. The guidelines are mixed a little bit on this technique at this point, it's a little bit immature and I think there's limited technical expertise, but I think in the next few years, this will change. There's little adult data for rections. I do know that this is something that comes up once in a while. And I think for me, what I've noticed is certainly there are some patients post COVID that are developing PVT, but what is the true indication to perform an elective tips in someone where some of the indications may be a bit more nebulous than those that are certainly much more clear cut than what Virginia was presenting. I thank you for your attention. Okay. So I'd like to thank everybody for attending and our two speakers for really cutting edge presentations about sort of emerging indications for tips and contemporary approaches to this. We have a lot of good questions in the Q and A, and I just want to remind everybody in the audience to please put them in the Q and A if you'd like me to ask our speakers any of your questions live. So I have a bunch of questions for both of you. I'm going to start with Virginia and go back a little bit to sort of the first half of the webinar. And so I have one question for you, which is when you're going to create a tips for a patient, let's say with ascites and elective tips, what is it that you're targeting to try to maximize your efficacy? Are you looking for a pressure gradient, a change in pressure? Are you looking for a stent diameter? And how has your thinking evolved as the technology has evolved with the stents? Thank you very much for this question. This is a very important one. And I think it's well, it's obviously a different setting, ascites versus variceal bleeding. And then in the ascites setting, you can be more conservative. So the aim at my institution, we always aim to reduce the portal pressure gradient, and we do like the technique guide with the reduction in the portal pressure. But there are some studies coming from Italy, saying that dilating or under dilating the stents can be also enough in this kind of patients, but you have to be very, very careful because the ascites, even if you open up the tips a lot, then you won't control, this is not something that you won't control right away. And the patient may require a lot of or a close follow up and tightening of the diuretics during follow up. So my recommendation is like go for a small diameter tips, do not over dilate in these patients and try to guide the response by the reduction in the portal pressure gradient. And then if it's not enough, you can always doing the follow up. We kind of like that they so do another procedure, go again, catheterize the tips and open up a little bit if you think that it's not enough. So it would be very conservative in the ascites scenario. And just one follow up question to that is when you measure the gradients, do you measure it from the hepatic veins or from the RA or another place? Because this is something I think we also debate, especially in the United States. Yeah, this is also have been a matter of debate. So it's different if you are measuring HBPG than the gradient. If you want to, we have a lot of literature about threshold and the risk and stratifying the risk and the prognosis of the patient. If you want this cutoff to work on your patient, you have to measure the HBPG with the wedge and the free and the free hepatic vein pressure in the setting of tips. You have to measure that with the inferior vena cava and the portal veins, the PPG. And if you measure that with the atrium, then there is a difference in the final gradient that it's not correlated as well as with the inferior vena cava when you look in the prognosis. So free and wedge in the hepatic vein for HBPG and vena cava portal vein for the GPP. Okay, great. Next question I have is for Dr. Salem. And I think as we get through the questions, we're going to talk a little bit more about the portal vein recanalization. But in terms of some of these sort of preemptive type tips indications in the United States, just my general feeling is we're probably not using it as much and especially in the child to be patients in the preemptive setting. And I wonder what the approach is at Northwestern. Is this something that has been a discussion with the hepatologist there? I think it's like you mentioned, I think there certainly is a lot of interesting discussions about that. I think obviously it gets individualized. I think we have a group that is for preemptively tipsing these patients. I think there's an equal number that are as vociferous as to potentially not accepting the risks of that procedure. So I'm not sure it's a completely answered question. Certainly from a technical standpoint, there's no difference from our perspective, but it's whether the indication is truly there. Yeah. Virginia, do you feel that the uptake for that indication for tips has been pretty good in Barcelona or in Europe in general, or do you think that now the new recommendations are going to help us move in that direction? I think it's challenging, right, to be able to do the tips in 24 hours. And this is something that you need. We need to work on how to derive patients and how to organize the whole thing. So it's not something as easy as giving Carvedilol to our patients that you can implement from one day to another. This requires a lot of compromise from our institutions and also transferring between institutions. So I know that I work in a place that it's probably that do not reflect the reality because here we have a dedicated ICU and the pathologies, we are placing the tips and we have a mnemodynamic unit only for pathology patients and only for doing this kind of things. And of course, we can do that and we can come every morning and see if we had any admission and needing tips, but this is not the real work. And we have been working a lot in Barcelona and in Spain, trying to organize the circuit of deriving patients and trying to implement this, but there is still a long way to go. I think in that same vein, I think you showed some nice data that maybe we shouldn't be so nervous about people, at least with a moderate elevation in bilirubin and some of the other parameters, maybe HE in the past, things that make us really nervous as hepatologists, but is functionally speaking, is there a bilirubin or a MELD cutoff that would make you nervous in that situation, perhaps, especially in the preemptive setting where it's not emergently life-saving? Are there cutoffs that you use clinically? This is a super good question and we have been working a lot on trying to identify other ways of identifying patients at risk, because calculating the childhood at the moment of admission, we all know that can be challenging and it's not like as good as the MELD that you have the parameters and then you have one number. But when we have been, when we try to see if the MELD was able to predict or to select the population that benefit from TIPS, we were not able to establish a cutoff that really works better than the child population. And this is why we keep, stick to the child B plus minus active living. And then for bilirubin, it depends, right? If it's only bilirubin, this is something, if you have an ACLF patients, like very same with a high bilirubin and many other things, maybe you have to think careful, but if it's only a race on bilirubin, this is the data that I showed you from the MEF analysis, so individual data, I think we should go for, we should go for TIPS. Yeah, great. So I'm going to transition for a minute to some of the PBR questions here. So I'll start with Dr. Salem. So one question that has raised in a couple of different ways, is there any safety issues we need to be thinking about with the splenic approach and or maybe even the mesenteric approach versus the usual TIPS? And in particular, one question that was raised, is there any risk of pulmonary embolism in this approach? And do you generally, you know, what is your anticoagulation practice during and after the procedure? So one of the things that we learned, certainly in the non-cirrhotics, the, you know, they all have relatively normal platelets in general, if not sometimes even elevated, but what we've noticed is there is no added risk. We use ultrasound, like I showed you before, we have not had any major bleeds. Sometimes we've noticed because we've gotten a scan several days later, just to identify patency of the TIPS, some minor fluid around the spleen. So there's certainly something there, but nothing hemodynamic that affects us. In the cirrhotic patient population, we did have a couple of patients that had sort of moderate bleeds because they're different. Their platelet counts are 30, 40, 50, their INRs are two, three, whatever it is. And you're trying to open something up so they can get a liver transplant. But we have not seen that with a frequency or severity enough to stop us from doing that. And the ultimate, of course, gatekeeper of that in our center would be the transplant surgeons and the hepatologists. And this really has become our standard. So yes, they're higher risk, but now with advanced techniques, advanced ultrasound, et cetera, you know, that risk is significantly diminished. And in terms of the PE, no, we have not seen, we have not seen PE. All of this stuff in general tends to be chronic, organized, clot at the fibrosis level now. So it's not really acute clot that's going to go anywhere. So no, we have not seen that. And do you use, you know, heparin or do you use something more specific during the procedure itself? So this is, this is the tough part. This is the part that we're still learning a lot in the non-cirrhotics. The problem with the hypercoagulable non-cirrhotics is if you have to do advanced techniques to your question, if I stick the IMV or the SMV or do multiple punctures, I can't have them fully anti-coagulated because then I'll cause a bleed. And so there are some cases where, um, you know, we were probably a little too shy on the anti-coagulation and they thrombose a little quickly. And so what sometimes I've now gone to doing is limit anti-coagulation because it's a high risk procedure. If I'm sticking the IMV or the SMV and then start them two or three days later, uh, sometimes that tips will have thrombose, but what I will do then is just open up and thrombectomize that tips on full anti-coagulation because I've done all the hard work. So sometimes the hard work is the first case, higher risk, don't anti-coagulate because you have to be careful for bleed. And then if they thrombose, cause I showed you that KM curve, right? It drops pretty quickly. There's some thromboses, then you anti-coagulate them and then you thrombectomize that tips on full anti-coagulation. And that's how you get that secondary high patency. And for the patients, um, the cirrhotic patients, then are you basically only doing this in the context of transplant candidacy? And, um, how do you follow the patency of the, of the intervention? And finally, more or less, what is the usual time between the procedure and the transplant? So in general, yes. I mean, these are transplant patients. We haven't really done this, uh, in the non-transplant patient. We have maybe a few cases where we're not sure he's going to end up with a transplant, but has, you know, horrific ascites or see if we're going to try to improve that. Um, so that, that tends to be, um, uh, sort of what we've done in terms of, um, following the patients, uh, early in our experience, all of the patients had a one month venogram. That that's how I know what they look like after a month. I don't necessarily do that all the time anymore, but I learned a lot doing that showing that, you know, um, you know, 30, 40% of patients have some clot at the end of the procedure and it's gone a month later, right? So you don't have to chase that stuff. And no, it was not associated with anybody with, with, uh, with, uh, pulmonary embolism. There might've been one case with a, with a small branch, but again, nothing of substance, uh, that, that made us change, you know, our approach and our follow-up in general tends to be in these patients, you know, they're being followed up again, most of them for transplant, right? So they're either getting imaging or ultrasound and, or both. Uh, and, um, and that's how, that's how we know what these patencies are like. And how long usually until transplant or at least average in your, in your own cohort? There's, there's a handful of patients. There's a handful of patients that actually went to transplant relatively quickly, uh, within less than a month. Uh, and, uh, but the majority of them, I think in that paper that we published, I think is about six months or 10 months, something like that. It's not, it's not immediate, but again, these patients are all prepped for transplant. They don't need an emergency one, but we prep them and they're ready to go in case of a decompensation. Okay. And Dr. Hernandez, is this an approach that's been attempted or utilized at all in, in Barcelona or in Europe? So we were fascinating, uh, fascinated when we, uh, saw, uh, these cases and, and, and yes, so we started to do a following, uh, we had data and we started like doing that at our institution. Numbers are lower than in, uh, Chicago, but, but yes, I think that this is something that when you select very carefully, uh, the cases, uh, can, can change completely the scenario and transform a patient that it's not candidate for liver transplant and you cannot offer them anything, uh, to someone that can be a transplanted. So I think that the learning, learning curve is significant and it's not something, uh, every case is different and it's a real challenge. Uh, but I think that this is, uh, this is the future. Right. One other technical question for Dr. Salem is whether, um, you're also doing these cases for the uradil class threes and fours and, or, you know, obviously if there's more mesenteric involvement, how does that change the complexity? So for a transplant patient, you know, if, if there's no inflow, I mean, it's the, it's the transplantation itself. That'll be the issue, right? Is that, is that if you can't get good inflow, um, you know, the theory of the, of the PBR tips in the cirrhotic is that I'm just fixing the main portal vein. There has to be good inflow so that when that's done, the transplant will stay patent. So in general, no, um, that's not what we, what we target. Although I think we had, I think, uh, 20% of our patients had uradil class three. So it depends how much a clot. And of course the, the non-cirrhotics, you know, a lot of them, you know, the 70 plus percent of the patients have SMV and, and, uh, and splenic vein clot. So they're all much more, much more thrombos. But the idea in that case is just to reestablish a straight line between the splenic vein out the tips that that's the issue. Right. Right. Well, I think we're going to have to conclude our questions here. Um, thank you for all of the many people who attended this and for the great questions in the Q and a, and I'm sorry if we didn't get to every one of them, but we will try to keep a record of that and get back to you for sure. Um, I'd like to really thank both of our speakers for a fantastic presentation. I think the number of people that attended this, um, really is a Testament to both of your expertise and experience. Um, I'd also just like to remind everybody quickly that the next, um, portal hypertension SIG webinar is also already scheduled. It's on April 12th and it's on endovascular versus endoscopic management of gastric varices, which is better, which I think is another really hot topic. I'm sure both of you would love to comment on, and we hope to see you there in the audience. And I also just wanted to remind everybody that the portal hypertension SIG also has a program at the upcoming DDW. Our program is on May 21st, and it is also related to portal hypertension, complications of cirrhosis, and in particular management of GI bleeding related to portal hypertension. So a lot of similar, similar themes will be presented there as well. So thank you again to the speakers and for everyone's attention, and we hope to see you at the next webinar.

ASLD webinar

Applications of Tips for Portal Hypertension

transjugular intrahepatic portosystemic shunt

TIPS placement

portal hypertension

refractory ascites

acute variceal bleeding

portal and mesenteric thrombosis

portal vein recanalization TIPS

chronic cavernous transformation