Melanie Cole, MS (Host): There's no handbook for your child's health, but we do have a podcast featuring world-class clinical and research physicians covering everything from your child's allergies to zinc levels. This is Kids Health Cast by Weill Cornell Medicine. And I'm Melanie Cole. Today, we're highlighting billary atresia in children.

Joining me, we have a panel for you today. Dr. Angela Kadenhe-Chiweshe, she's an Associate Attending Surgeon at New York-Presbyterian Hospital Weill Cornell Medical Center, and an Associate Professor of Clinical Surgery at Weill Cornell Medical College, Cornell University; and Dr. Adriana Perez, she's an Assistant Attending Pediatrician at New York-Presbyterian Hospital Weill Cornell Medical Center, and an Assistant Professor of Clinical Pediatrics specializing in pediatric hepatology and liver transplantation at Weill Cornell Medical College Cornell University.

Doctors, thank you so much for joining us today. Dr. Perez, i'd like to start with you. For listeners who may not have heard this term before, tell us a little bit about what biliary Atresia is, why it's such a serious diagnosis in infants. When you explain this to patients for the first time, Doctor, the simplest way that you describe what's happening inside their baby's liver.

Dr. Adriana Perez: Well, thank you so much. First off, I want to say thank you so much for having us. It's such a pleasure to be here and to have this opportunity to really inform parents and colleagues and general pediatrician about this important topic.

So usually, when I get to talk to parents about biliary atresia is when I get called to a child with a high what we call direct bilirubin. And at that point, typically of the first contact, we don't necessarily get to yet talk about that for certain this will be biliary atresia. But biliary atresia is definitely highly on our differential in all babies who have high direct bilirubin, particularly those babies who also have pale stools, who are not growing well.

And so, typically, in this situation, which I do want to say it's a team sport, me and Dr. Chiweshe work very closely together when we meet this family. We tell them that it's possible that their baby is going to have or is at-risk of having chronic liver disease. And that's really why it is so important that we work this up. And we orchestrate sort of this workup for them to make sure we make the diagnosis as soon as possible, to make sure that these babies have the best outcomes possible. So, that's sort of how we start.

I do tell them that any babies who have high direct bilirubin, there's a possibility that it's one of many other conditions that we will test for as well. And there's also a possibility that this may be something benign that goes away. In certain small percentage of patients, that happens. So, that's sort of the first encounter.

But once we really do have the diagnosis, once we've orchestrated the whole testing, and we had completed the testing, then why is it such a serious disease? It's because if we do not address this condition with a surgery that these babies need, these babies go on to have chronic liver disease. And truthfully, prior to us doing this surgery that can improve them, these babies died before the age of two years of age.

Melanie Cole, MS: Okay. So, thank you for explaining a little bit about that. And Dr. Perez, I'm going to stick with you for a second. From a pediatrician's perspective and a specialist in liver transplantation, speak a little bit about why this condition could be devastating if it's not caught early, but which symptoms should never be brushed off as normal in a newborn. When we're talking about jaundice, is there a critical window of time? Speak to parents about what it is that you're noticing, that they're noticing, that their pediatrician is noticing, that would signal that this could be something rather serious.

Dr. Adriana Perez: So, any babies who are jaundiced should not be brushed off as being breast milk jaundice, because breast milk jaundice is very common, and it is the most common cause of jaundice. But it's very important that every pediatrician does the blood work at two weeks of life for those babies who remain jaundice and takes a look at the type of bilirubin that these babies have.

Because we have the total bilirubin, then we can divide it on something, what we call direct and indirect. The indirect is benign. The direct may mean that there's something going on with their liver. And unless they check, they'll never know. Babies with biliary atresia, and I kind of skipped that part. What biliary atresia really is, is that babies are born without their bile ducts. So, I always tell to the parents, the baby's liver is like an apple tree. We have the tree with the branches, and then the liver cells are the leaves on the tree. And so, babies with biliary atresia, they don't have that apple tree developed. It's small, it's fibrotic, it's not present. And so, the liver cannot appropriately drain bile-- bile is fluid that the liver makes-- out of their livers. And that bile intoxicates the liver. It leads to scarring, it leads to fibrosis. And over time, it leads to liver failure if it's not addressed. And the way it is addressed is the surgery that I've mentioned before.

And so, those babies are going to have high bilirubin because the bilirubin cannot leave the liver, and it gets absorbed in the bloodstream because blood is trying to help out the liver. And then, they're going to have pale stools because the liver is not draining the fluid bile that is designed to color our poop brown and color our urine yellow. And so, without that biliary tree, this isn't happening. And so, babies have pale stools because bile isn't going, and they have very dark urine because all that bilirubin is being absorbed into the bloodstream, and then colors our urine because of that. And so, if that critical period of about the first two to three weeks is missed, then babies go on to develop what we call failure to thrive. They don't gain weight.

And if that is not picked up, and they can of course continue to be jaundiced and if they come even later, if, let's say the pediatrician doesn't realize at two months when they see babies that the baby is jaundiced and does not notice that the baby's weight isn't really where it's supposed to be, and these babies somehow slipped or fall through the cracks and something happens, if this continues, and by the time these babies are four months old, they do develop large bellies because the livers get very large. The spleens get large. They have big vessels in their bellies. Parents can see these blue hues within their abdominal wall. And so, those are the classical signs of biliary atresia

Melanie Cole, MS: Thank you. So, Dr. Chiweshe, for families hearing about surgery at just a few weeks of life can really sound overwhelming, speak a little bit about what types of surgeries, procedures that you do for these babies. We'll get into transplantation in a minute. But before we do, tell us a little bit about procedures that you might start with.

Dr. Angela Kadenhe-Chiweshe: Right. And thank you, Melanie. I want to reiterate what Adriana said at the top of the hour that we are so grateful for this opportunity to speak to our colleagues, to parents, families out there who are listening about this really, really important disease-- important because early recognition, timely diagnosis speaks so far into outcomes from the surgery standpoint. And also, we know that it's the leading reason or indication for transplant in children. And so, while we have made incredible strides with transplantation, and Adriana will talk about that later on, we are always looking for ways to diagnose babies early. Get them to surgery early because that is our best chance of having a baby maintain or keep their native liver, the liver they were born with for as long as possible. And there are huge advantages to that.

But a couple of things that Adriana touched on before I go into the surgery, number one, by the time we are called to see the child who is jaundiced, time has elapsed, the baby has been jaundiced in a lot of situations. And as Adriana pointed out, breast milk jaundice is the most likely. cause it's the most common reason why a baby is jaundiced. And kind of like when we deal with children with constipation, right? A very, very common diagnosis. But if you don't think of other potential reasons why a child could be constipated, you will miss it.

Similarly, if you don't think of other reasons why a baby can be jaundiced, you will miss it. So, the teaching for all of us in medical school, all of us as medical students, is babies who are jaundice beyond the age of two weeks deserve to have a test that differentiates their jaundice. I'll say that again. Babies that are at two weeks and who are persistently jaundiced deserve to have a test that will break down the bilirubin in their blood and tell us if it's all indirect bilirubin anemia, which is basically what is the cause of breast milk jaundice, or what Adriana pointed as being benign, or if it's direct hyperbilirubinemia, which is pathological. It'll almost always be pathological. So, that mark of two weeks of age is really, really crucial. Coupled with that will be things like, you know, what does a stool look like? Unfortunately, stool color fluctuates so much depending on what the baby is feeding, what mom is eating, what's in her breast milk. So, it's very difficult to rely on that.

And in addition, if you have urine that's very dark because of the jaundice, it can sometimes falsely color the stool. And as we know, babies poop and stool at the same time. And so, you can get some really false reassurances from just looking at the diapers. And if parents ever want to know what stool color should look like, there are several references online that will key you into what stool color should and should not look like. In this country, we do not hand out stool cards to families when babies are born. In other countries where biliary atresia is way more common, such as in Asia, every parent leaves with a stool card so that they can be aware of what the color of the baby stool is, and to bring any concerns to the pediatrician's attention right away.

So, that two-week mark again, I will say, is really important. So by the time we get called to the baby's bedside for a baby who's been jaundiced, it's a pediatrician or a family that have recognized that this has been going on for too long. Blood work's been done. And lo and behold, the suspicion for a pathological process has been raised.

Now, as Adriana mentioned, there's a differential. And at the top of that differential, a differential meaning that there's a list of causes potentially for that direct hyperbilirubinemia, but always at the top of that differential will biliary atresia, one through ten. The reason we say that is because this diagnosis is so highly dependent on early diagnosis and early intervention for as best of the outcome as we can possibly attain.

So, our focus in the first few days that we meet a baby that now has been confirmed to have a direct hyperbilirubinemia is focused on working up this child for biliary atresia. And that workup involves doctors that include more beyond just myself and Adriana. There's hepatology, which is Adriana represents; pediatric surgery, which I represent; interventional radiology, diagnostic radiology, nuclear medicine pathology, so that we have a team that is always ready and waiting to basically descend upon this baby, so to speak, and do all the interventions we need to do to very quickly make the diagnosis or rule out the diagnosis if we're fortunate, because ultimately the goal is to get to surgery.

The current and only surgery at this point for this diagnosis is the Kasai portoenterostomy, otherwise known as a Kasai procedure or portoenterostomy. There are different terms that people will float around, but generally most people will hear Kasai. If parents were to Google or ChatGPT and they put in Kasai, it'll usually give them everything that they need to know.

The Kasai procedure was created kind of serendipitously in Japan decades ago, and found its way to the United States in the '80s through one of my previous mentors, Dr. Peter Altman. And essentially, the goal of the procedure is to restore flow of the bile. Adriana is absolutely correct in that the liver is like an apple tree where the leaves are indeed the hepatocytes that make bile, and the branches then coalesce into bigger branches and ultimately into the trunk, and that's the flow of bile, which ultimately needs to enter into the intestinal system in order for us to be able to digest food. So, bile is critical to our ability to digest food and, more importantly, to absorb fats, especially essential fats that are crucial to the development growth, especially brain development in babies. So, bile is very, very important and it has other factors and functions that I won't necessarily go into.

But I had one father, actually, when I explained in my process of explaining biliary atresia, he gave me his analogy, which I thought was great. Imagine driving on I-95 and you are trying to merge onto I-95. And you can't merge onto I-95 because I-95, there's a traffic jam with a car accident maybe at Exit 50, and you are at Exit 40. And you at exit 40, you can't get onto I-95 because of the accident that the police have blocked the entire interstate. That's the obstruction or the blockage that biliary atresia causes in the bile duct system, mostly outside the liver.

So now, we have a backup of that traffic on I-95 from Exit 50 all the way to Exit 40, Exit 40, all towards the little roads that basically feed into Exit 40 and so forth and so on. And I felt for that father, that analogy-- and maybe he's a car lover, I don't know-- but that really seemed to resonate for him. And it pretty much sums it up. The biliary tree outside the liver, it's a progressive process of biliary atresia, it's progressive in terms of the inflammation, the fibrosis, and ultimately the obliteration of that bile duct system that drains bile from the liver. It's always ironic the liver makes bile, but it absolutely hates to store bile. It's never meant to have bile sitting there. Bile needs to flow.

So, the whole goal of the surgery of the Kasai is to restore that bile flow. And the best way that we can do it is to essentially remove all of that extrahepatic obliterated fibrotic bile duct system and connect the intestine directly to the liver, directly to the liver plate where the intrahepatic bile ducts are draining into, where initially they were draining into that obliterated extrahepatic valve that now we are just basically bypassing all of that extrahepatic stuff that has no pathway, no lumen, and bringing the intestine right up to the liver.

 And it sounds like it's a straightforward operation, but obviously there's a lot of technical prowess to it. There are very important maneuvers that we have to do during this process to ensure that we do the best possible operation. Once that surgery is done, that surgery for the most part is well-tolerated, and we have a very systematic and protocolized postoperative course for most babies. It is an operation that's done under general anesthesia. But because we are so facile at it, we have developed, again, another team including anesthesia, ICU, pediatricians, hospitalists, liver doctors, surgery doctors that all come together to take care of the baby around surgery.

But as I said, most of these babies will tolerate the surgery very, very well. It is often very scary for a parent to think of how their four-week old baby or six-week old baby can get through surgery. I will tell you that, as pediatric surgeons, we are trained to take care of preemies that weigh 500, 600 grams. We are trained to take care of neonates at three kilos. We are certainly capable of taking care of babies at six weeks, four weeks, all the way up to 17-year-olds as well. So, this is our training. The size of the baby is not really the issue. It's just making sure that the baby is relatively healthy enough to get through the surgery, which most of them will do.

Melanie Cole, MS: Well, thank you so much. That was such a comprehensive, understandable answer and really such a multidisciplinary approach, which is so important. And thank you for explaining that to us. Now, Dr. Perez, for families living in that in-between space when a child is headed towards transplant, I'd like you to speak about what that looks like for the families, because really that is an anxious time, a terrifying time. And as Dr. Chiweshe was just saying, you're really good at taking care of these little tiny babies. And so, that should be very reassuring. But for parents, it certainly is terrifying. So, tell us a little bit about what that's like, how you work with those families in that in-between time and what the long-term outcomes look like for children that do receive that liver transplant.

Dr. Adriana Perez: I do want to say that a hundred percent, it's a very terrifying period for the parents. They are sort of always on the edge of what's going to happen next with their child. But I think before we jump straight to the transplant, I do want to say that in-between period may look like those patients who do receive this life-saving surgery, the Kasai, about two-thirds will be initially successful, and I'll say what that means. And then, about one-third of patients will not as what we call drain their Kasai, meaning this surgery will not establish bile flow in the intestine. And those patients will go on to transplant much faster, typically under one-year of age. And I'll in a second say how does that look like.

And for those patients who do sort of "drain" their Kasai, then among the two-thirds, majority of them slowly and slowly between the age of five and ten, they will run into trouble with their livers. And again, I'll say what that means. And then, about 25% of kids, or 20% of kids overall who received Kasai will go on beyond 18 years of age, and they will receive a liver transplant sometime later. And so, how does that look like? I think the first group that never drained their Kasai whose livers will get-- really, they do develop what we call end-stage liver disease in their first year of life. That's an extremely terrifying period. And those babies, we focus on, weight gain because they don't gain weight. They're very jaundiced. They're highlighter fluorescent yellow. They develop what we call ascites, they have fluid in their tummies. And all these things that I'm stating are essentially indications for liver transplant.

And so, here at Weill Cornell, we talk with the families. We work very closely. I see these patients closely every two weeks, every week if we need to. And we work together and decide when's the optimal timing to select liver transplant. And about 50% of our liver transplants are done via living donor where a parent or a friend or whoever can give a piece of liver to someone's child. And that really allows us to find the best timing for liver transplant.

Melanie Cole, MS: This is such an interesting topic, such a fascinating topic. Now, I'd like to give you each a chance for a final thought. Dr. Chiweshe, speaking to parents about what they can expect, what the outcomes for these babies are, what the rest of their life looks like, and how you are helping the entire family when you're working with them on the emotional, the psychosocial, all of the aspects that go into this kind of diagnosis. Give us a look to the future and what's in store for these families.

Dr. Angela Kadenhe-Chiweshe: So, I always start out every counseling session with these families with one fact, which is the overall survival for your child is greater than 90%, regardless of how things work out whether you get a Kasai that drains forever, whether you have a Kasai that drains for a little bit, whether you have a Kasai that doesn't drain and you have to go to transplant sooner, these babies all do well overall. The odds are in their favor.

And the reason why that is, is because of the strides that we have made in the multidisciplinary care. There's ample literature that supports the fact that high volume centers with multidisciplinary teams has been an absolute game-changer for these children. So as devastating and as daunting as the journey is, and it is, we will get you to where you need to be with your child. We expect them to go to college, we expect them to be obnoxious teenagers, and that is our goal for you and your family and your child.

We have ample support. We have recently started a program where we have psychologists and psychiatrists that focus specifically on families that are going through complex surgeries. And this has been an a real great addition to our social workers and our nurse practitioners and our child-life colleagues, both on the inpatient, outpatient side that rally around these families and really hug them and hold them throughout their journey from infancy all the way to wherever they need to be along their journey. So, we are always hopeful, and we are here to certainly help anyone who is going through such a diagnosis.

Melanie Cole, MS: And Dr. Perez, last word to you. When you look at where we are versus 20 years ago, what gives you the most optimism about the future for children with biliary atresia? What gives you the most hope when you're caring for these children and watching them grow up?

Dr. Adriana Perez: Personally, I love this field. I love seeing these kids growing up, seeing them in clinic when they were so sick, and then they come and they are doing so great. It's such a joy. And what gives me the most optimism for the future? I think it's working with this fantastic team, working with Angela and the entire team that we've mentioned that we have; the close collaboration, the innovation, the people trying their best, and seeing how modern medicine is advancing technology is advancing surgical techniques are advancing. Every five years, we're better and better in what we do. So, the future, I think, looks good for these kids.

Melanie Cole, MS: Thank you both so much. That was fascinating. So much great information, and you are both such great educators. I imagine the parents are very happy to be working with you both and that multidisciplinary team. Thank you so much for joining us.

And Weill Cornell Medicine continues to see our patients in-person as well as through video visits, and you can be confident of the safety of your appointments at Weill Cornell Medicine. That concludes today's episode of Kids Health Cast. We'd like to invite our audience to download, subscribe, rate, and review Kids Health Cast on Apple Podcast, Spotify, iHeart, and Pandora. And for more health tips, go to weillcornell.org and search podcasts. And don't forget to check out Back to Health, so many great podcasts there as well. I'm Melanie Cole. Thanks so much for joining us today.

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