Why Children and Teens Need Liver Transplants

Dr. Richard So, MD:

Welcome to Little Health, a Cleveland Clinic Children's podcast that helps navigate the complexities of child health one chapter at a time.

In each session, we'll explore a specific area of pediatric care and feature a new host with specialized expertise. We'll address parental concerns, answer questions, and offer guidance on raising healthy, happy children. Now, here's today's host.

Dr. Senthikumar Sankararaman, MD:

From the moment you get your scary diagnosis to the days spent waiting on the liver transplant list, caring for your child with liver disease is something that impacts your entire family. I'm Dr. Senthikumar Sankararaman, a pediatric gastroenterologist at Cleveland Clinic Children's. And today, we are talking about liver transplantation.

We will explain why a child might need a new liver, what to expect during the surgery and hospital stay, and how the latest developments are helping kids live completely normal lives after transplantation. Joining me is my friend and colleague, Dr. Mike Leonis. He's the medical director of our pediatric liver transplantation program at Cleveland Clinic Children's, and who specializes in the treatment of liver diseases. Welcome to Little Health, Dr. Leonis.

Dr. Mike Leonis, MD:

Thank you.

Dr. Senthikumar Sankararaman, MD:

Before we go on to the episode, tell us a little bit about your background.

Dr. Mike Leonis, MD:

I've been at the Cleveland Clinic Children's since 2020, so I'm relatively a brief duration relative to the duration of my overall career. I was born and raised in Las Vegas, Nevada, and after high school went to St. Louis, Missouri, where I did my undergraduate MD and PhD at Washington University in St. Louis. Thereafter, I did my pediatric residency in Salt Lake City, and then my pediatric GI fellowship at Cincinnati Children's, where I remained as faculty until 2017. Then I had a brief stint at University of Birmingham, Alabama before joining Cleveland Clinic, as I mentioned. Why return back to Ohio? It's because it's where, for my wife and I, we have perfect four seasons. We love to garden. We like nature. It's very green and lots of rivers and lakes where we live so we can go out and be with nature. And we also like to travel a lot, in addition to being amateur foodies.

Dr. Senthikumar Sankararaman, MD:

And we are happy to have you with the expertise you bring from all the, the great centers you, you worked. So tell us about what are the most common reasons a child might need a liver transplant?

Dr. Mike Leonis, MD:

So in pediatrics, there's actually a large variety of reasons that children might need liver transplant. Overall, it's a rare need, but there could be hundreds of potential diagnoses. The most common would be maybe 25% of the cases might be those patients that unfortunately are born or shortly after birth develop a condition called biliary atresia. That's where the plumbing coming out of the liver, the biliary tree, scars down in a very rapid pace within the first several months of life, which then sets the liver up to fail. It can't excrete the toxins that the body produces into the bile, and that is not a condition that a, a, an infant can survive in. Other major causes or reasons for a need for liver transplant could be the development of some kind of liver tumor. That's actually probably the second largest reason at Cleveland Clinic Children's for more typically older child or teenager needs a liver transplant.

And then there's a variety, a long list of metabolic conditions. There's acute liver failure that it pops up on occasion that drives us to liver transplant for some kids.

Dr. Senthikumar Sankararaman, MD:

Are there any medications that could potentially lead to acute liver failure?

Dr. Mike Leonis, MD:

Yes. So, you know, potentially any medication taken in great excess has the capacity of being toxic to some organ in the body. The most notorious, commonly available medication that can harm the liver is acetaminophen. In normal doses, the liver handles this very well in normal recommended doses, but on occasion, patients take excessive amounts or in an attempt to harm themselves. Sometimes teenagers will take a very, very large amount of acetaminophen, and that is very prone to be harmful to the liver. Thankfully, there's an antidote for this if, if the patient is found to have done this early on in the clinical course. Unfortunately, a large subset of these patients don't inform their family members that they've done this un- until three or four days afterwards, and then the antidote is not as effective. On rare occasion that those patients need a liver transplant.

Dr. Senthikumar Sankararaman, MD:

Thank you. Could you tell us about, like, what are all the symptoms or manifestations that indicate a child's liver is failing and medical therapy is no longer working and we have to think about, , it's time to move on to liver transplantation?

Dr. Mike Leonis, MD:

So unfortunately, most of the symptoms, early symptoms at least, of liver disease or injury to the liver are very, what we call non-specific, meaning it's hard to distinguish whether those symptoms are coming from liver disease or just a viral syndrome. For example, symptoms of fever, of vomiting, of feeling in, , having malaise, of feeling crappy, decreased energy, all those things overlap with a viral illness, but could be the first signs that potentially there's problems with the liver. Probably, , the symptom that is more specific to liver disease is if you see the presence of jaundice or yellow in the, in the whites of the eyes or in the skin on the face or chest.

If you see that, then for sure you're gonna be focused initially on is this a, either a liver or a bone marrow hematologic process. If you ever see yellow on a child, it's not normal, except in the very first, first few weeks of life in the newborn period that in, on, on all circumstances that needs to be assessed by a physician. Even in the newborn period, they should be following along to make sure that it resolves in the normal fashion.

So that's why when you go to your healthcare provider, if they're concerned with how you look or you go to the emergency room and they're concerned with how you're, you're behaving, they will get a comprehensive metabolic panel, a routine blood test that assesses the liver for injury markers. And if those are elevated or the bilirubin is elevated, then of course they know what to do next, which, which is to further assess liver function metrics and/or call your friendly hepatologist if, if those are abnormal.

Dr. Senthikumar Sankararaman, MD:

And we know you work closely with a, with a transplant team. Tell us a little bit about how that process works. Once your transplant is decided, tell us about what UNOS is and work with the transplant team enlisting the kid, things like that.

Dr. Mike Leonis, MD:

So fortunately, most kids that have liver disease do not end up needing a liver transplant. Those who do need a liver transplant are really very few. I'll pick a number. I'll say 0.1% of those that might have some kind of liver disease might end up going to the point where their liver is failing or is not going to get them through the rest of their childhood or the rest of life, which case there's criteria that we use to decide whether or not we think that patient needs a liver transplant. Once our team, it's a multidisciplinary assessment. Once we have completed a multidisciplinary assessment, if we decide it's best for that child to undergo a liver transplant after we go through our committees and, and voting and recommendations on how to optimize care, if it's still thought transplant's the best option, then if we vote to list someone, then they go to a national listserv, so to speak.

It's a big computer that anonymously houses all the patients across the, the nation that our center and other centers have decided need a liver transplant. And those patients are ranked based on blood type and then a scoring system called a PELD score. Generally speaking, that's how the majority of patients are decided on who's sickest, who need, has the most urgent need for any available liver that becomes available or to, to use in a patient. The PELD scoring system is an attempt to, in a quantifiable way, compare patients based on their lab test abnormalities in children, whether they're growing appropriately for their age. So the sicker your liver, the higher your PELD score, the increased chance that you will get a liver offer compared to someone with a lower, lower PELD score. Patients can wait a week once listed for a liver transplant or a month or several months.

It also depends on the comfort of the surgical team in accepting organs as they become available. Are they comfortable doing split liver transplants where you take a partial piece of a liver from a, an adult donor or a larger size patient and you can splice that into a small child and every surgical team has different criteria for what they will, are willing to do. So that influences how long someone might be waiting on, on a liver transplant waiting list. In addition, at Cleveland Clinic Children's, we have a fairly novel, large program called Anonymous Living Donor Liver Transplant Program. So in addition to being able to use pieces of liver from a living patient wherein the adult patient typically donates a portion of their liver that the surgeon uses for the child, and adult's liver will grow back to size within a month or two post-surgery.

And traditionally that's a living related donors, meaning a friend or a family, close family, a close family member or friend of the patient offers, raises their hand to help out the patient. But here at Cleveland Clinic, we have this anonymous living donor program where good Samaritans can raise their hand, come in, be evaluated and make sure they're healthy, make sure their liver vessel anatomy is appropriate toward safely taking a piece of their liver and using it in another. And not un - infrequently, these people, these good Samaritans like to target their livers to children. So my program, the Pediatric Liver Transplant Program, benefits from that generosity in that shortens our waiting time dramatically. So compared to the other centers I've been into, been at in the past, my kiddos here don't have a wait, they really don't have a significant wait time because we are, are willing to do LRDs, living related donors and anonymous living donors at a higher rate than other centers.

Dr. Senthikumar Sankararaman, MD:

That is so wonderful to hear and so grateful to those donors. So what does the medical team do to keep your child healthy for the surgical transplantation while they are waiting for a transplant?

Dr. Mike Leonis, MD:

So again, our goal is to avoid liver transplant if possible. So if we have the luxury of time in taking care of the patient before their liver gets sick, we try our darnedest to keep it from getting to the point where it's end stage liver disease. So depending on the liver condition, that might mean optimizing immunosuppression to keep the liver injury from progressing, as an example. But if the kid's liver becomes end stage, meaning it's, there's only one way at this point, then we, our focus is really on nutrition, up trying to maintain the optimal nutrition so to increase their chances of success through the surgical experience, the transplant surgical experience. And all the while as well, we are optimizing their immunizations because post-transplant, they are going to be initially highly immunosuppressed, which makes them vulnerable to all infectious processes, but in particular, those that we have these wonderful vaccines to mitigate and avoid serious morbidity and mortality like mumps, measles, and rubella and varicella or, or chickenpox, otherwise known as chickenpox.

For the very young infants, sometimes we can't get those vaccinations in and that just raises our concern, our angst. But post-transplant, once they get to a lower immunosuppression, sometimes we can catch them up on some vaccines. So to optimize their health as much as possible, we focus on nutrition and immunization pre-transplant.

Dr. Senthikumar Sankararaman, MD:

Thank you. So now, , moving on, let's say that we have a kid who just underwent liver transplantation. I know you work closely with the ICU team as well as the surgical team. Tell us about like what happens in the first initial few days. I know not only for the family, but also for the caregivers, it's, those days are very crucial. We have a lot of milestones we kind of watch for. For our families, could you help us kind of kind of understand like what exactly kind of like happening there, what things the medical team is looking for, things like that.

Dr. Mike Leonis, MD:

Once a donor has been identified, we bring the patient to the hospital and usually the day before the intended day of the surgery, the surgical experience is about a six to 12 hour experience. Our surgeons are very meticulous and do a great job of optimizing the anastomosis that they're gonna have to connect up to five vessels, sometimes more. The liver, the veins going in and out of the liver, the hepatic artery, the bile duct all needs a conduit has to be established in the patient's body to the, those five areas in the liver graft. So they take their time and we benefit from that in that we have reduced amounts of return to the OR post-transplant. Immediately post-transplant, because this is a major surgery, as you mentioned, the patient is very closely monitored in the intensive care unit for typically, I'm gonna say five to seven days post-transplant.

And immediately we're worried about one, does the new liver wake up? Very rarely, it doesn't. There's criteria we use to decide if that's the case, but the vast majority time, 99.9% of the time the liver wakes up just fine. And then we worry about plumbing problems, okay? No obvious plumbing problems in the operating room as they come out, otherwise they would've addressed them there, but sometimes they present themselves a few days later. And initially as well, we are worried about acute, rapid, fulminant cellular rejection of the liver where your immune system wakes up and says, "I don't like that foreign body that was just put in here," and it goes under hypermode and attacks it. That rarely happens as well. We have to watch for it because that's especially aggressive. So we need to really hit the body hard if that, if we see that happen with additional immune suppression.

Most commonly though, it's smooth, relatively smooth sailing. None of the things I just mentioned happened. The kiddo comes out of the intensive care unit five to seven days and then they're, then they're on our step-down unit for another one to two weeks on average. And we are always watching in it for surgical problem complications as well as medical complications of the immune system, of the kidneys, infectious disease metrics are being monitored weekly, sometimes if needed more frequently, depending on whether there's a fever or signs from blood tests that there might be an, a brewing infection. So the average patient, maybe 80% of patients are discharged after maybe two to three weeks from their transplant experience and then monitored closely as an outpatient. And the better they do, the more we wean them away from us. So there's, the visits become less frequent. Initially, it's twice a week or once a week with twice a week labs.

And as time goes on, we can hopefully at one year post-transplant, they are at the point where there are eight to 10 medications that they are discharged on, get whittled down to one or two by one year. That's our, my goal that I carry in my head. Not every patient reaches that goal. Some of them have problems during that first year post-transplant, as you well know, you take care of them as well when you're on inpatient service with me or with us. But the majority do very well and we don't have to readmit them to the hospital. The majority do just fine on the outpatient where we can get down to every six months or even in rare cases, once a year visits. And the patient can return back to normal functioning, resume virtually any activities that they dream of doing as if none of this has happened, except for the fact that they have to stay in close con - they have to be compliant with seeing us in clinic, getting routine monitoring so we can monitor for rare things like cellular rejection and they do have to take immunosuppression as far as we know, the vast, vast majority for the rest of their lives.

That's a separate research area whether or not there are some patients who someday will be able to come off immunosuppression, but generally speaking, that's not standard practice quite yet.

Dr. Senthikumar Sankararaman, MD:

Thank you, Mike. That was a very clear explanation I have heard. So I have a question about the rejection. Oftentimes we hear about acute chronic. Could you tell us a little bit about what the differences are or what signs parents should look for and how they can prevent?

Dr. Mike Leonis, MD:

I'll tackle the last part of your question first because that's the easiest part. Unfortunately, there are no signs for the family to be watching for when they're at home for either of these types of rejection that you mentioned. It's silent in the m - vast, vast majority of cases. Sometimes there's, you know, I've read reports, people say, "Oh, well, you have a fever." Well, that probably was a viral process that may be triggered of a rejection episode, but most viral episodes of the patient gets post-transplant don't lead to a rejection episode. So reject, that's why we monitor with blood work so closely. When the immune system is freshly dealing with this new transplant, you're more vulnerable to the immune system attacking that liver. And it's as time goes on, as the, your native immune system gets used to that new liver, then it's less prone to attack.

So we can lower immune suppression as time goes on and see how the immune system behaves. Acute cellular rejection, acute means sudden onset. Cellular means that it's driven by immune cells, most commonly T cells in the body, that are driving the rejection response, as opposed to there's other kinds of rejection, antibody mediated rejection, which is also needs immune cells to help generate the antibodies. But the thing that's attacking the liver cells are antibodies circulating in the bloodstream, just like antibodies will try to, to get generated to, to mop up and clean up viral infections, right? So the classic sudden onset early post-transplant rejection flavor, as you will, is acute cellular rejection. And if we d, we detect that by monitoring blood labs that look at the liver enzymes, if we can't explain a sudden rise in the liver enzymes and we go through a little algorithm to look for alternative explanations and we can't find a source for that increased liver enzymes, then we suspect it's acute cellular rejection.

And the way to confirm that is with the liver biopsy, which is a simple procedure done in the hospital. If the pathologists look at the liver tissue and say, "This looks like consistent with the cellular rejection," then we typically will bring the patient in for a five to seven day course of increased immune suppression, hitting them with steroids to quiet their immune system. And usually that's sufficient to make it go away. So a rejection episode, one out of three patients has a rejection episode in the first year of post-transplant. It's very common for us. So we're, we are d-don't get too flustered by it. We try to minimize that. We want to make sure immunosuppression is optimized to avoid that, but it does not mean that the liver is done or it's a one or two or three episodes. But if it keeps going on and on or it becomes very low grade, you can shift over to chronic rejection, which is a little harder to detect because sometimes even your liver enzymes can be close to normal and you can have chronic rejection.

So, or we never get back to a, a normal baseline again. And that chronic rejection then leads to different histologic findings on the biopsy. A long period of chronic rejection can cause enough damage to the liver over the course of one, three, five or 10 years to the point where a patient may need a re-transplant. 10% of patients need a re-transplant within 10 years post-transplant. That gives you some idea of the rate of failure of the new liver. So on occasion, someone needs a second transplant down the road.

Dr. Senthikumar Sankararaman, MD:

I think you bring a nice point, like close follow-up after the transplantation, but it seems like as time goes on, the intensity or the frequency of the follow-ups gets lighter and lighter for the families.

Dr. Mike Leonis, MD:

Yes. And one of the biggest problems we have is patients get transplanted when they're young, when the child is a young child, and then they do so well that either the patient or their parents get complacent, "Eh, we don't have to... Maybe they missed a few days of their immunosuppression and they got repeat labs and nothing happened and we didn't end up calling them because we didn't see any changes in the labs and we don't know that they missed some doses." And they say, "Well, maybe you don't need to take this immunosuppression as much as the doctor says as you do." Or they have a flare of rejection and no huge sequelae occurred as a consequence and they're like, "You know, this happens once every five years, but I'm okay." And I, they get non-compliant or complacent in their teenage years. And teenagers, as you all know, everybody knows, tend to have a, a little bit more bravado bravery in, in doing things that are higher risk, don't like to listen to authority figures sometimes.

And that leads to sudden deterioration of the liver, silent initially and until it's not. And when it's not, that means it's too late for us to, to turn it around. So we have a, I have compared to my other patient populations in pediatric GI, a higher rate of non-compliance in our older patients where I think they just get burned out with the burden of having a chronic disease for the 20 years. And they don't remember the pain and suffering because it occurred when they were too young to remember. Sometimes the parents remember, but the patient doesn't. So it doesn't mean as much to them to be diligent. Not all of them, 10% maybe. And that 10% is a huge number compared to, as you know, for so many of our other patients with diseases, chronic diseases that we take care of. So that's kind of a sad thing.

It makes transitioning to the care of adult caregivers all the more difficult. That's always a difficult transition anyways. We have to do it at some point in their early 20s.That's the time period we typically transition to adult care. And when, when we have the patients that are already like starting to demonstrate non-compliance, ooh, does it make it hard to make a transition? Sometimes we're caught between a rock and a hard place of what to do or the, the, the patients will move, they'll change locations of where they live and sometimes don't give us time to set things up and that's where transitions get lost too.

Dr. Senthikumar Sankararaman, MD:

Yeah, I agree. That age group is really vulnerable and at the same time, it's also very challenging to manage. Yeah. Anything else you'd like to add, Mike?

Dr. Mike Leonis, MD:

I think the final point I'll emphasize is that this is rare. The vast, vast, vast majority of patients out there, even if a doctor someday tells them that their child's liver enzymes are elevated and there's something going on with the liver, to need a liver transplant is gonna be a rare occurrence. But unfortunately when it happens, it is very serious, just like being diagnosed potentially with a cancer or a malignancy. So we have to, thankfully, we know enough about what to do nationally. And so the large medical centers have physicians in place and teams in place to, in a multidisciplinary fashion, address all the needs of someone who has end stage liver disease and/or someone who's undergone a liver transplant.

Dr. Senthikumar Sankararaman, MD:

Thank you, Mike. I'm so, as a gastroenterologist, I'm so thankful to you guys, like working with one of the most vulnerable patients and taking care of you work closely with the surgical colleagues, ICU colleagues, infectious disease colleagues to manage all the complications and all the nitty-bitty things you mentioned. We are so thankful for your work.

Dr. Mike Leonis, MD:

You're welcome. Thank you. It's our pleasure. It's what we're here for.

Dr. Senthikumar Sankararaman, MD:

I'm sure, as your parent, if you have your child with your liver illness and listening to this episode, we hope we have helped you a little more prepared and you're not alone in this journey. Our experts like Dr. Leonis and the entire team, we are here to help you. If you have any questions about liver or liver related illness, and if you would like to schedule an appointment with your pediatric gastroenterologist or hepatologist at Cleveland Clinic Children's, please call us at 216.444.KIDS, K-I-D-S, that is, 216.444.5437. Thank you so much for listening.

Dr. Richard So, MD:

Thanks for listening to Little Health. We hope you enjoyed this episode. To keep the Little Health tips coming, subscribe wherever you get your podcasts or visit clevelandclinicchildren's.org/littlehealth.