Approaches to Biliary Atresia Care at Cincinnati Children's - Amy Taylor, MD - Successes in collaborative management of the post-kasai patient

Um, but let's, um, our last speaker and certainly not the least, is Doctor Amy Taylor, um, who, uh, I've known also for a very long time, is also a Cincinnati lifer. Um, but Amy currently is the program director, um, for the Pediatric Advanced, uh, hepatology Transplant Fellowship here at Cincinnati Children's, of which she is a graduate. And uh she is also the leader of ALink, as, which is a learning health network focused on improving the outcomes in pediatric autoimmune liver disease and is the PI for uh A Link's Multi-enter prospective registry. Uh, her research focus is on utilizing quality improvement methodology to improve patient-centered outcomes in liver disease. And today, Amy will be speaking to us about um success in collaborative management of the post-Kasai patient. Thank you so much. I appreciate that kind of introduction. Um, so it's my job to kind of wrap it all, uh, uh, put it all together, um, and I have no disclosures. Um, so thinking through how to optimize outcomes in biliary atresia, we've kind of walked through, um, referral timing, looking at how do we expedite and make the correct diagnosis, what are the surgical and technical considerations for, um, for surgical management in CASai. And I'm really gonna be kind of talking through the post-Kai care, um, with kind of an eye on how do we optimize this piece of it, um, in light of all of the other, other things that we have discussed. Um, so there have been multi-center studies largely through the Children Network, um, predicting early post-Kasai outcomes, and you heard kind of this, uh, discussion as well of, you know, uh, a total bilirubin less than 2 at 3 months after Kasai predicts 2-year outcomes, and this is that data. So, um, this total bilirubin level was associated with better transplant-free survival. Um, so 86% of those who had a total bilirubin less than 2, had a better transplant-free for survival at 2 years of age versus 20% of the bilirubin was over 2. They also had better growth and better weight gain, and you can kind of see the, the survival curves in blue with patients who had, um, Who, who had lower bilirubin and then in red, those who had higher. We also, the Children Network also looked at predicting late post-Cassa outcomes, um, looking at children beginning at 2 years of age. So we know that kind of total bilirubin at 3 months of uh post-Cassa has some association with outcomes, but what about at 2 years? And so in this cohort, 240 children with BA who had their native liver at 2 years of age, um, had a medium follow-up time of 5 years. Um, 38 patients had a liver transplant in 1. Death and prognostic factors that were identified kind of associated with kind of better transplant-free uh survival, um, were having, um, lower total bilirubin levels, less ascites, less likely to have cholangitis, higher albumin, and better platelet counts, and you can kind of see the risk stratification here in group 4, and you can kind of see that this is how they looked at these factors within these groups. Um. So these are kind of, you know, we look at not only survival, uh, with native liver overall survival, but how are kids doing after, um, after Kasai kind of neurodevelopmentally. And so this is a study that Vicki Ying did with the Children Network, looking specifically at the Bailey examination for neurodevelopmental, uh, development, and this was utilized in 148 children with native liver after Kasai. They did 132 exams at 1 year, 85 at two years, and they looked at um kind of factors associated with um decreased scoring. So, physical and motor impairment um was uh associated with having ascites and a lonely disease score. Um, those who had a more, uh, mental, cognitive, and language impairment at 1 year old, um, were more likely to have had ascites and a low weight Z score. And then an unsuccessful Kasai hepatoroasty was risk of impairment in both domains at 2 years old. Um, and so this kind of, we, we looked at this data, um, looked and thought about how do we implement this, how do we Um, incorporate this into our post-Kasa management, in addition to kind of all of the other things that my colleagues have talked about to optimize, um, going into and during the surgical case. And so when we think about this, um, I think about kind of collaborative management. Um, it, it's not an accident that we have both our hepatologists and our surgeons on this year together. We work really closely together. Um, and we also work closely with our inpatient, our outpatient, and our patient and caregivers. And so when I think through the phases of care of where patients are engaging with the medical system, I think these are key areas for improvement. And so I'd like to highlight some of the things that we have done in strategies within our inpatient team, and this all highlights an implementation of clinical protocols and the outcomes associated with that. Um, some proactive management of nutrition, and really, I think multidisciplinary care, which is hard to quantify, um, but it's very important for outcomes. I'll highlight kind of our outpatient team who has been a mainstay of, um, the early recognition of changes in clinical status for our patients. We have, we work with a Highly collaborative nurse and admin team providing consistent reliable care. We look at all of the patients before they come into clinic through pre planning and timely communication. I'll go through these things. And also working with our patient and caregivers, um, making sure that they have anticipatory guidance and education that, um, we are communicating well with them, that they feel comfortable and have the means to. Uh, share early, early concerns. Um, and also they have the resources and support because we know that this is a, this is a good deal. It's a lot of work to take care of an infant, um, but to take care of a medically complex infant who is going to have chronic medical needs, including post-op care, um, this, you know, specter of liver transplant, um, providing the framework of support for them is critically important. So looking at our post-Cassiah care, um, we focused a lot on this, and we had some protocols that became more formalized in 2017 that I'll go through, um, in published work. Um, but immediately postoperatively, kind of, our patients, um, if they're young, so if they're in kind of that 30 to 35, 40-day window, um, we have a routine of these patients going into the PICU for the first About 24 hours afterwards to ensure just because they're little, um, also to make sure that they, um, the pain management support, the, the, the, the, the closer monitoring. Um, other than that, they'll go to their surgery service. Um, we have separate hepatology service. Our team, um, consisting of the attending and a fellow and usually a transplant fellow will see the patients daily, and we will talk daily with the surgical team. Um, patients will get routine postoperative care. Um, this includes IV sufoxitin for about 3 days. There's an ongoing assessment of nutritional intake once patients are able to take PO. Um, we have a low threshold to increase the caloric density of their formula while they're hospitalized. We check and then aggressively replete fat soluble, uh, vitamins for deficiency, and we have incorporated a SOS therapy protocol for higher dose, um, vitamins, um, with a, with, with repeat checks for these patients. Um, Doctor Teo, uh, alluded to this, so all stool diapers are inspected. They are saved. There is a Sharpie with time and date on them. Um, and we all look at all of them. Um, and so that's part of our morning rounds routine is we will look through all of the stool diapers with the team. Um, we'll talk about it with our surgeons, and then we have a protocols in place for persistent acolic stools, but we sometimes we will escalate IV antibiotic therapy and consider steroid therapy in select cases. Um, Doctor Tail also mentioned that we often will have the stool color card in the room, um, and we will also send it home with the families. So, kind of getting into, is there a role for steroid administration, and I just highlighted, this is um the, the group um from the UK who kind of summarized the, the previous studies for steroids and looked at the two reneized control trials. So, the start um group from the, from the Children Consortium and the King's College Hospital trial. Um, and kind of the, the timeline for those, and you can kind of see, um, the, the design, the centers, um, the number of subjects and controls, and then you can kind of see the steroid regimen, and I just would highlight that there are differences in the steroid regimen, um, that were utilized in the Um, the mean age of Kasai was, was different, um, between the two groups. Um, the main outcomes we're looking at, uh, bilirubin levels at 6 months, and then overall outcomes looking at transplant-free and overall survival. Um, I would highlight that the SART trial that in kids less than 70 days, um, 72% versus 57% of who would receive steroids tended to have better, better outcomes. It was not statistically significant, and I would highlight that in this King's College cohort, um, they showed that steroid administration in, in the younger cohort defined as kids less than 70 days, um, had better outcomes. And so we assimilated all of this, and we, we talked as a group, um, long and hard. Is there a role for steroids, and if so, how? And ultimately, we kind of came up with a consensus, and I, um, would highlight Doctor Vier's role in this, um, and acknowledge Doctor Yamataka, um, at Tokyo, Japan, who helped with, um, as we devised this protocol. Um, so basically, and then, uh, Doctor Pandaranji, uh, published our, our, our results, our early results from this. So the protocol was implemented. Um, it was crafted and implemented in 2017 at Cincinnati Children's. This was distributed both to the hepatology and surgery teams. Again, we have daily discussion regarding the stool color, uh, collaborative decision for steroid initiation, and this looked at 20 sequential patients with VA, um, compared to the historical controls. And so basically patients underwent conai, we evaluated the stool uh stool color. If there were acolic stools in patients who were less than 45 days, there was seemed to be, um, in the SART trial and, in, in the King's College, that the younger kids with steroids tended to do better, and so we escalated IV antibiotics and IV corticosteroids after identifying that there did not seem to be any infection. They're over 45 days if they had liver inflammation on their, um, On our biopsy, and we also looked at the Kasai, um, remnants, we would do IV antibiotics and corticosteroids. I would just note that we typically will do a biopsy before going to intraoptic cholangiogram Kasai, and so that hence kind of the reliance on inflammation. If patients had normal stools, they were discharged on, on antibiotics. Um, and then this, as you can see is our steroid protocol. So it's kind of a, a mixture of, of high and low, um, but really it's kind of a steroid burst in the course of. 5 days, and then a gradual 25% reduction over the 4 weeks typically as an outpatient. We would escalate antibiotics to include typically Piproil and Tazobactam. If there's any concerns for uh renal insufficiency in the patient, then we would do cefepe Flagyl typically. Um, and then outpatient, we would treat with, um, Augmentin. If there's any concerns for cholangitis, then sometimes it would escalate, but typically, this is where we would start. So what did, what, what did this, this show? So, um, basically looking at a historical control of patients, um, pre the new protocol, um, there was no statistically legitimate difference in the baseline factors. So the median age of Kasai was between 50 and 55 days. In these groups, there were no baseline, uh, demographic changes differences between the groups, and there were no, um, statistic differences in baseline liver biochemistries. Um, and you can see that in red, these were the successful bile drainage as kind of a continuous chart here, and then implantation of the new protocol, you could see that we had, um, more successful drainage. So this again was defined as a total bilirubin less than 23 months after Kasai, 84% versus in the new protocol versus 40%. And then, um, basically in those we had data for over 2 years, 11 out of 16, so 69% were alive with natal at 2 years versus about 50%, and this did not, uh, achieve statistical significance, but was a trend for it and potentially not powered for this. You can see this here. So, we just kind of did a, a re-review, um, looking at our patients, or our past patients in the past two years. Um, and so we had 9 patients who came, um, who were offered a Kasai, and of those, 8 out of 9 or 89% had successful viral drainage. The median age at Kasai was 53 days, and you can see the range here. We talked about 29, and I think that uh Greg alluded to doing some later Kasai, so there was a patient at 109. The patient, um, who underwent, um, Who, who did not have drainage and has actually undergone liver transplant, um, presented, uh, with at ausa about um 8386 days of life. So clearly this early, this early, um, hospitalization is important, but there's a lot of care that happens once patients are discharged, um, and ongoing collaboration in this outpatient setting, and I wanted to highlight some of the, the things. So I would like to highlight our role of the inpatient team, both our surgical colleagues, the surgical APPs, surgical fellows who were there, as well as our inpatient team, including the residents. Um, we have a very talented and gifted. Um, a group of advanced practice providers who are frontline providers for these patients who, um, have implemented these protocols, who, um, look through every stool diaper with us. Um, and then I'd, I'd also like to highlight the role of the outpatient team. So once patients are discharged, we have routine hepatology follow-up post-Cassa. They come to the hepatologist. It's often every 1 to 2 weeks early post-Ca. We have protocolized laboratory monitoring. We actually have order sets built in our EMR to make it easy, um. We do nutritional assessments including RD evaluation, consultation. We look at MULAC, we look at, um, Z scores, we, you know, uh, make sure that we have patients who are thriving nutritionally, um, and do routine assessments for fat soluble vitamins. Um, I would just note that we have a cadence of doing weekly pre-visit planning for patients coming up in the next 2 weeks and then post-visit assessment, and this is our hepatologists, our liver nurses, our liver admins, and if we have any concerns, our surgeons are very available. We pull them in as well. I think that for these patients and families, and also highlighting uh what Anna presented in terms of disparities in outcome, identifying that there may be more resources that are needed for support for patients and caregivers. We have dedicated liver social workers who work with us inpatient and outpatient. Um, we have philanthropic support for a vitamin fund because in terms of medicines, a lot of these times, fat-labeled vitamins are not covered, um, transportation assistance and really being sensitive to how do we work with local providers and partners, especially for patients who come at a distance, partnering pediatricians with gastroenterologists. Other hepatologists to make sure that patients, um, the burden of having to come physically to our center is not too much. Um, we educate, empower caregivers, we facilitate in communication, so phone, EMR messages, uh, Doctor Tia talked about all the stool pictures we get and we ask for them. Um, And then the um early recognition of, of clinical change and assessment and intervention, and this really goes to, um, I would just highlight our outpatient nursing team who are highly educated, highly skilled, and wonderful resources for our patients and families, um, who are able to, you know, say, yes, this is a concern, you know, catch early patients who are developing early signs of cholangitis, so we can get these patients back in, um, uh, back in, um, To see us, uh, treatment of early cholangitis, um, as well as nutritional concerns. Um, and so I just kind of like to highlight that it really has, does take a village, and I think, you know, I'm focusing on the things that we're doing post Kasai, but really, a lot of these same groups of people are working at every level of the spectrum to improve and optimize outcomes for our patients. So with that kind of in mind, thinking through, um, kind of globally, how can we, you know, optimize all of these different things, recognizing there are still needs in, in, in the field in terms of diagnosis, in terms of understanding the idiopathogenesis of this, in terms of optimizing, um, care, recognizing that each center has a relatively small number of patients and how do we learn from one another. Um, and I just like to kind of highlight the role for collaboration for these. All right. And I'd be happy to take any questions. Thanks, Amy. Wonderful to summarize all the great work that everybody on this, on this call was or on the presentation was um highlighting, how it is step-wise, how we try to integrate horizontal horizontally, vertically, all of it in the best care of these patients. So, uh, Cecilia, I think we have a, um, a poll question for Amy's piece. And so while everybody, um, gets a chance to look at this, um, And answer the poll question. I'll start with, we have a few um uh questions in the chat. First, Amy, I'm not sure, I'm not aware of this study, but Maria Chikoff says, uh, do you have any thoughts on the new Chinese study by Liu and colleagues from this year recommending routine post-op steroids? Are you, are any of you familiar with that study? So I can, I can jump in from kind of some of the, the studies, um, from the START trial and also who, who kind of looked at the outcomes, uh, of, of those. And I think some of the concern that we've had in routine postoperative use has come from the START trial, recognizing that um there were similar numbers of postoperative, of, of complications including cholangitis, infectious risk after, after Casa HPE. Um, it happened. Earlier and sooner in patients who underwent the high-dose steroid protocol. And I think that's where we're trying to decide that, you know, you have patients who have undergone a surgical procedure that there is a risk for infection as well as not only inflammation. And I think that we, um, we have been cautious in the use of, of steroids, um, recognizing that I think there are some, you know, some multi-center stud. That we've been a part of that showed that potentially the efficacy in a broad group of patients may not be, may not be as beneficial and potentially harmful. I think that, uh, you know, I should say that, you know, we make it seem like we have the protocol. What I will say is that this is, we have ongoing discussions with every patient before we start them on steroids. This is, you know, we look through all of, we look through all of it. It's a surgical decision. We will pull in kind of Actually all of our colleagues. And so we have, we have this protocol, um, but we also want to make sure that it is also tailored, and I think that's how, uh, Doctor Pandri brought it as a customized, a customized therapy. There is an algorithm, but really, as we know that, um, biliary atresia seems to be heterogeneous in terms of we know that patients come to us at different times with different stages of fibrosis, and we are sensitive to that as well. Perfect. Amy, I'm gonna jump in here and just add a couple of comments back cause I don't think we want to send out the message that everybody should get steroids post Cassat. I think the START trial was properly conducted. It was properly powered. It showed that there was no benefit to, um, to, um for steroids in a well-designed trial. So, our evolution was primarily driven by a couple of younger kids who we thought they should have gotten drainage. And this is where, you know, the customized side to this is. The goal of our steroid um utilization is not to say every patient gets a cassai. I mean, Steroids. And in fact, you know, that patient that Amy alluded to was our last kid who had a cosign. It was 83 days and she didn't have any findings that would make us think there was a lot of inflammation going on. And even though she had slightly pigmented stools, we did not use steroids on that patient. And so I think this is really a critical piece for the audience to, to recognize that there is the use of um steroids, if, you know, that's why I say to our, our ped surgery fellows, um. If you, if, you know, get asked that question on your boards and say you should use them, you are, that's not the way I would want you to go out there because that study was properly done, properly designed. But there are a subset of patients, and this is where it wasn't powered enough to capture the, the smaller infants that we're now trying to get the size to. And that's where we do think there's a potential role. But if you have a 60, 7 day old, 70-day old kid who, you know, is, is showing up with sporadic VA, you know, we would not be using steroids. OK. Um, so, let's review the poll question while we have a second. So, um, Doctor Taylor asks us which of the following is true about the relationship between outcomes after Kasai, uh, and biliary atresia and bilirubin level. And so I think we had final 52% saying that a total bilirubin of less than 2 g per deciliter 90 days post KSI is, is associated with improved transplant-free survival. Amy, what do you think? Yup, that is the correct answer. So good job, guys. And this is just a highlight, um, kind of what I work with when we work with our fellows too is that we also, you know, when we're looking at diagnosis biliar tissue, we're looking at the, the direct bilirubin, and this really highlights that it really is the total bilirubin, um, that seems to be, to, to be this, and it, and it's a pretty, it's a pretty narrow range, right, um, of a total bilirubin afterwards. And so I kind of wanted to highlight that. Yeah. And again, similarly, As Greg mentioned already, that's the criterion we would use to consider a patient for revision as well. So, it's a, it's a metric that is used in the literature and we use it obviously in our own clinical practice. Um, so sorry, to clarify, you use total bilirubin for this, right, because most of the people, so like the majority were a total, but a good portion of them answered direct bilirubin, so. Yes, yes, it's total bilirubin. Perfect. Which translates to the direct should be lower. And Um, Doctor Campos asked for the protocol, so I included Doctor Pandaranji's, uh, paper that we all participated in, um, that we can share around with everybody. Um, we have a question from, uh, Doctor Matcovici. What is your view on using probiotics post-KSai? Or do you, you guys have a strong feeling? So I will say that we clinically do not typically use them um in this setting. Um, I think that we, I, we have looked at the role of, of antibiotic therapy, at least in our, in our group, in our cohort, and have seen um beneficial there. I don't know if anyone else would want to comment on And their thoughts, uh, for this. I know that we, um, get a little nervous oftentimes in the neonates, a lot of times these kids will have a central line, um, to manage them in the postoperative setting, the risk of potential uh infection and just kind of our concern of using this in the neonatal pillet period, but I would open it up to colleagues too. I do think it's an evolving field though. Georgie, of course, and, and others have shown that. The immunological response to the, the, uh, bilio obstruction is uh uh very much driven by the microbiome and, you know, experimentally, of course, uh, feeding, you know, the maternal diet, the feeds to, uh, the, the, the pups in the experimental setting, made a big difference on, you know, what type of immune cells would respond. Uh, to the bili obstruction and you know, there's been, uh, some early translational data on the microbiome, how it shapes in, in humans. So I do think there's a rationale. I think there are some smaller clinical trials. It's just like with, with most of the microbiome interventions, we don't really quite understand yet in which, in which direction to intervene and how to do it, uh, successfully and reliably. But I think the microbiome, that, that is a, that is the next frontier after the, the selioppoarchy. Alex, you mute it. Sorry, Alex, we have a question from Doctor Dio Gracias about how long do we keep our patients on, uh, antibiotics post Kasai. So, great question. So, um, I think that there are like treatment antibiotics and then post and then we would also think through like prophylactic antibiotics. Um, So we would typically, um, while patients are inpatient, we typically will do treatment antibiotics. Um, I think it diff it it differs in our protocol whether patients are draining or not, right? So in patients who aren't draining, um, who may or may not go through the steroid protocol, we will do treatment. They're on prophylactic antibiotics throughout the duration of, um, the steroid course, as well as, um, Uh, antacid therapy, um, our patients are typically on ursodiol, um, and then vitamin support. Um, for patients, um, who are well draining, um, I think it's, it's, it's again kind of part of this customer we typically will send them home on kind of a, a two-week course of antibiotic, and then depending on how the patients are doing, um, we will, we will tailor the therapy from there. Certainly, in patients who have had recurrent bouts of cholangitis, they, um, will get, uh, Um, we'll get antibiotics. We typically try to, to start, to start with the minimum antibiotic that we can, right? Um, and so we typically will think through Augmentin and then escalate to, uh, Bactrim and then potentially escalate further if we need to in terms of prophylaxis. But I think the antimicrobial stewardship, especially in patients who are, you know, maybe looking at transplant situations, is a really important thought, um, and it's one that we take, um, we take into consideration to try and minimize the antibiotics where we can. Yeah, there was actually just, just published this like last week, a meta-analysis and JPGN about the use of uh post-Kai antibiotics. Now, incredibly heterogeneous as the, as to the administration, dosing, etc. But their conclusion, the investigators' conclusion was that there's no role for antibiotics post Kasai. But again, with a lot of the other questions we brought up there, um, Uh, there's room, certainly room for a randomized trial to answer that question, and maybe it would happen in the context of a whole package of post-Kasai, uh, care paradigm that, that Doctor Taylor had proposed, you know, showed everyone how we do it. But I, I do think, uh, You know, Billiard Treia, I think, is a, is a great example of how difficult it is to draw conclusion from multi-center trials meta-analysis. I think we, we are ourselves here surprised that you can actually make a difference without a magic bullet, but there's more the belief that Uh, failure of Kasai is unacceptable, and every, every cholangitis, every hint of cholangitis prompts, uh, an immediate action and an intervention and, uh, an assessment of what is the best treatment. Um, coming to the, uh, the micro question about antibiotics and cholangitis, I think the Children Network has shown that The rate of cholangitis even in the patients older than 1 year of life is still 15%. So, um, in my mind, there is, if they tolerate Bactrim, and not all of the patients tolerate Bactrim, I've seen, uh, leukopenia, agranulocytosis, uh, so I, I'm, I monitor that relatively carefully. Uh, but I usually keep them on it as long as they tolerate it, given that, um, cholangitis concern. I also want to make a comment that the um the Japanese group data showing that the Kasai uh outcome can be improved, but the overall like 2 years and 3 years of the transplant rate um is actually closer to uh Uh, US data. So, I think we, we, we've seen that very change, dramatic change of Oskar site right now, but I think we need to be very careful watching our patient population for the next couple of years to really, uh, see the big picture of this uh change. You're muted, Alex. Still muted. I still muted. Sorry. Um, uh, for Greg, what is your opinion on curettage for intractable cholangitis? So I think that ties to the Kasai revision question. And, you know, um, it is one of the things that we pushed our GI colleges to see whether they could actually retrograde get up to the hilar plate to, To do that scraping. Uh, we have some very capable interventional DI colleagues on top of the ones on the call. But the Casai revision is not a re-cutting of the hylar plate. What you're really doing is just curettaging that, that plate to remove it. Um, any of the debris that has built up on it. We're not taking down the whole anastomosis. We're really just taking down the anti-mesenteric side of it to, to look into that area, um, or not, I guess not. You're really all closer to the mesenteric. So you have to be a little careful about it. We've also I also had a couple of patients where the recurrent cholangitis was due to a little blind loop that had arisen distal to, not, not, you know, with the drainage side, really in the staple side of the root where that area had kind of gotten patchtuless cause there was, had been good drainage. And those are the kids where we'll go in and we'll resect that redundant um tip of the root. Um, and then, you know, uh, thereby eliminating uh a possible area of stasis. Some of the recurrent cholangitis kids, of course, will be on Flagyl first and all these other things in an effort to try to suppress any blind loops, um, symptomatology. Um, and so, it's a, it's a, a, a thing that we'll be looking for if we're going to the OR for recurrent cholangitis. And, and just from a technical perspective, when we teach our fellows how to build the portoenterostomy, we only go several millimeters away from the stapled edge of the bowel, uh, trying exactly what, what Greg is saying, not to leave a spur of, of blind-ended bowel, you know, to the medial aspect of the hilar plate, so as not to promote bacterial overgrowth or stasis. Well, I think if there are no more questions, we wanted to thank all of you for joining us and hope that, you know, we learned something or um that some of the issues in this complicated topic at least have bring some, not clarity perhaps, but at least a little bit um of the flavor of how uh we've approached this disease, this complicated disease process. So, again, Uh, I wanna thank all the speakers and appreciate their time and effort and to all of you in the audience, um, who, uh, who joined us today. And remember, if you need CME credit, uh, you can jump back to the front page and click on the button, uh, and then eventually this, a recording of this symposium will be available.