Cori Cross, MD (Host): Welcome to Peds Cast, a podcast
brought to you by Children's of Alabama. I'm pediatrician, Dr. Cori Cross.
Today, we are joined by Dr. Marcos Pozo, who's the Surgical Director of the
Pediatric Liver Transplant Program at Children's of Alabama. He'll be discussing
biliary atresia and updates from a transplant perspective. Dr. Pozo, thank you
for being here with us today.

Marcos Pozo Jatem, MD: Thank you very much for having
me.

Host: So, let's start big picture. Give me a broad view
of what biliary atresia is and how common it is.

Marcos Pozo Jatem, MD: So, it is basically what I like
to call the zebra in pediatric, specifically in pediatric surgery and even in
pediatric liver transplant. A zebra is what we call in medicine that rare
disease that you, more often than not, think that it won't be the diagnosis.
However, it's such a big zebra in pediatrics in my mind, because the
consequences of not diagnosing it or diagnosing it late are very, very much
cumbersome and important. They have a many effects on these patients.

And the reason why I call it one of the biggest zebras in
pediatrics is because, even though if you do think about it and you do diagnose
it, the consequences of this disease are lifelong. So, it's disease that even
if you intervene early on, the parents are still going to be dealing with like
lifelong care for their baby, even as they move into adulthood. And statistics
do show that at least 90% of these patients will end up receiving a liver
transplant biliary atresia before they're 18 years old.

All that to say to basically highlight the relevance of the
problem, but biliary atresia, it boils down to a genetic defect with some
contribution from the environment. In fact, the etiology of it is truly unknown
still to this day and where the liver is born without a biliary system, meaning
there's no gallbladder, there's no bile duct inside the liver; and thus, these
babies already have cirrhosis of the liver by the time that they reach two to
three months, unless they're diagnosed early.

Host: Got it. So, early diagnosis is really key.

Marcos Pozo Jatem, MD: It is. It's extremely important
because what we know from the disease is that whatever affects the liver in
these babies happens in utero, is already when they're already are fetuses in
their mom's belly, something's already affecting their liver. So by the time
that they're born, we already have a fight against time because you have to
diagnose them ideally within the first days of life. And what confounds the
problem is the fact that it'll manifest itself with being jaundiced. And as
every parent knows, that being jaundiced in the early days as a newborn is very
much a common occurrence. And in reality, the differential diagnosis for this
is very broad. That's why, again, going back to the analogy of being the zebra,
neonatal jaundice may be from breastfeeding or the baby may need phototherapy.
There are many, many causes for it. And one of the last few in that list will
be biliary atresia, but it's one that you definitely do not want to miss.

Host: Now, some women are doing ultrasounds later in
pregnancy. Would this pick up biliary atresia?

Marcos Pozo Jatem, MD: Unfortunately, no, because
basically the ultrasounds may see the liver itself, but that's basically it.
This is an active area of research and doing studies in pregnant women trying
to correlate some amniocentesis findings and some inflammatory markers.
However, nothing has been proven yet that we can say for sure that there's a
prenatal diagnosis that we can do.

Host: And that's kind of because in utero you're not
actually eating, right? And then, it's not until you're out in the world that
your digestive system actually has to kick in. And so, the waterfall effect of
having the biliary atresia is when the digestive process starts. That's what's causing
all of the issues down the line.

Marcos Pozo Jatem, MD: You're absolutely right, yes.
Basically once you are born is when finally your liver kicks in. And we use our
bile to digest our food as part of our components to our bile salts. But yeah,
when you start nutrition as a new newborn, that's when the problems start to
arise because there is no bile to be excreted. The bile is just accumulated in
the liver, and that's when jaundice then begins as well.

Host: So besides jaundice, what are the first signs or
symptoms a parent or a pediatrician might notice?

Marcos Pozo Jatem, MD: So, the parent and pediatrician,
jaundice, it's relative. Parents may not notice it right away, or they may be
told at the beginning like, "Oh, your baby's a little bit jaundiced,"
which is pretty common immediately in the newborn period. But acholic stools is
a big buzzword in biliary atresia. Parents that notice their first diaper was
just whitish clay-colored stool, not really normal, then that is a big, big
buzzword that should prompt further investigation for sure.

Host: And when you say clay-colored, we're talking the
gray clay.

Marcos Pozo Jatem, MD: Correct. We're talking gray clay
or even whiteish. In fact, the subjective judgment actually on the color of the
actual stool is one of the biggest areas where personally I'm interested in in
developing this pilot program to try to improve the early diagnoses of these
babies. And it's a very simple solution. I wish I could take credit for it.
It's been proven wide to be very, very official in other countries. Japan was
the first country that instituted this with a pilot program in Taiwan where, to
eliminate this subjectivity, they just gave parents after they were discharged,
after having a baby, a stool card basically with colors and indicative as like,
"This is normal stool. This is kind of concerning. If this is this color,
call us right away," and to alert not just parents, but pediatricians as
well, because it included like, "This is what you need to do if this were
to happen."

Host: that's genius. Because if you were to say clay
color to somebody like my mother who's an avid tennis player, they're going to
think of the red clay.

Marcos Pozo Jatem, MD: Correct. And that's why we see
more and more, especially with babies that come to our clinic, late diagnosis,
like at the time, me as a liver transplant surgeon, I'm seeing them for an
evaluation potentially for a new liver because it's too late. More often than
not, I ask parents like, "What was the color of your baby's stool?"
And they all vary. The same buzzword. But when I ask them to point to exactly
what color was it? everybody has a different idea of what that is.

Host: You mentioned about this early screening idea.
Tell us a little bit about what you're trying to set up with an early screening
and early referral protocol.

Marcos Pozo Jatem, MD: Absolutely. I think it's a
combination of things. So definitely, the stool card is the primary idea of
this project where we educate parents and pediatricians like, "This is the
stool color and parents will call if they have this. And this is going to be
the protocol." Basically as early as possible, as soon as that is
detected, then the baby can get just a simple blood test that you can measure
the total bilirubin, but also get the direct bilirubin, basically the
fractionated bilirubin. Because the direct is the one that indicates a liver
problem, whereas indirect, not so much.

What I say it's a complex problem, I recently had a talk with
the American Academy of Pediatricians, the Alabama chapter, because I'm glad
that they changed our policies as well. It used to be that babies had a newborn
screening, then they had maybe a one-month screening or appointment with their
pediatrician, and then there was no two-month required. It was usually,
"Okay, skip until the three months when they were due for their
immunizations again." But then, a lot of patients, a lot of parents were
told in the newborn in the one month, "Oh, this color of stool, okay,
that's normal. We can keep track of it at the end." And by the time they
showed up for their three-month appointment, then the baby already has liver
cirrhosis. That's also a mindset change that is occurring right now. And I'm
glad the AAP is extremely supportive of this and they're also supporting of now
also even at two months well-child visit.

Host: And if you got the labs at the two-month child
visit, would there be babies that you missed because they hadn't presented yet,
their atresia wasn't so severe? Or if you were doing these labs routinely at
the two-month mark, would you really capture most of the infants?

Marcos Pozo Jatem, MD: You really capture most of them
because, by that time, usually they will have some degree of liver dysfunction.
What makes it a little bit more complex, and this is also part of the education
of the whole pilot program that we want to start, is that there is a pediatric
surgery procedure that you can do. It is called the Kasai portoenterostomy.
It's a very big fancy term, but Kasai was basically the Japanese surgeon that
described it. But basically in simple terms, you're connecting a loop of bowel
to the liver since they don't have those bile ducts. So, you're creating that
connection to try to drain some of the bile from the liver and to relieve it
from the burden.

Host: Once you do a Kasai, are you treated for life or
is there a reason for the infants to continue to have followup?

Marcos Pozo Jatem, MD: That's essential and I'm glad you
asked because that is a big perception that a lot of parents think that, "Oh,
once my baby already had the surgery, the end. It was a disease, but it's
cured. And I don't need any more followup." And sometimes, we see even
pediatricians that think, "Oh, they had the Kasai and that's okay."
But in fact, this is a lifelong disease and they require constant care. So even
if a Kasai is defined as successful, if after three months after the procedure,
then the bilirubin gets normal, and that's fine. However, at the end of the
day, these livers were not born normal. So even if the bilirubin itself
normalized, long term, these babies can still have sequela or consequences of
their liver disease manifested in what we call portal hypertension, meaning
that they develop collateral and they have varices in their esophagus, in their
stomachs, or they can be prone to having GI bleeds. They can have big spleens
as well. And long, long-term, this circulation that is abnormal, that is a lot
of blood flow that's supposed to be from the gut through the liver into the
heart that is totally abnormal in these babies, long-term can have effects
inside the liver and manifested years long with even liver tumors. And it also
has a side effect on the heart itself because it puts an extra burden on the
heart. And sometimes there's something called hepatopulmonary syndrome or
portopulmonary syndrome where kids, not babies, but usually when they're in
their teenage years, after years of having this abnormal circulation, they end
up needing oxygen as well.

Host: Got it. And so for someone who's trying to follow along,
basically, the liver, what's going on, and correct me if I'm wrong, is
basically almost like a plumbing problem. The liver's saturated with blood
vessels and the blood and everything that's supposed to be going through the
liver is sort of getting backed up, and so creating problems up the line for
things that are pushing against that liver and not letting everything go
through. And then, that affects things also down the line. So, it's like you've
got a little bit of a clog in the system, right?

Marcos Pozo Jatem, MD: Correct. Whenever I talk to
parents to explain the situation, I always equate it like a plumbing problem or
even like a filter in a sink that is clogged and that is a problem. Basically,
the clogged analogy is basically the liver being cirrhotic. Cirrhotic just
means scar by any cause. In this case, biliary atresia is the cause. So that
clogging, that's exactly like you said, Dr. Cross, it leads to the backing up
of all those blood vessels elsewhere. Blood has to go somewhere else.

Host: Let's just touch on liver transplant. So, you
mentioned that sometimes the children might need a liver transplant down the
line. Do you ever do a liver transplant just right off the bat?

Marcos Pozo Jatem, MD: That's a very good question, and
the answer is yes. The main thing is that whenever patients get at the
two-and-a-half, three-month mark, at that point, the Kasai, that primary
procedure to try to drain some of that bile may not be successful and, in fact,
may push them into acute liver failure if they already are showing signs of
cirrhosis at that point. So, sometimes we do have babies that are late
diagnoses or referred late to our transplant center that when they show up, the
question is, "Can we do a Kasai?" But sometimes they already have
that portal hypertension, that big spleen, those varices, that ascites. And in
those cases, then you shouldn't do the Kasai. Then, you will proceed with a
primary liver transplant, that will be their first operation.

Host: Does getting a liver transplant early prevent some
of the sequela that you talked about before?

Marcos Pozo Jatem, MD: It does prevent some of the
sequela because the liver transplant is curative. However, in pediatric liver
transplant, obviously, it's a highly technical, highly complex operation. Even
in an adult that when you boil it down, then you're going now with a baby, then
the stakes are much, much higher and it's more complex because of the size.

Host: Got it. But the good news is livers are easier to
come by.

Marcos Pozo Jatem, MD: Technically, yes. It's easier to
find because sometimes you can even split what we call an adult liver and give
part of that to a baby. But the donor pool in Alabama, sometimes people don't
want to donate or sometimes people have other diseases that makes them
inadequate donors for a pediatric donor specifically, especially in terms of our
diabetes epidemic, our obesity epidemic, that makes it sometimes slightly
harder.

Host: To find that healthy liver.

Marcos Pozo Jatem, MD: Correct.

Host: This has been fascinating. In summary, is there
anything else you'd like to share with our listeners today?

Marcos Pozo Jatem, MD: I think the main thing that I
would like to share just with parents, pediatricians and anybody that sees
these babies that have heard, "Oh, biliary atresia," or even just,
"They're a little bit yellow when they were newborns "and/or they
just noticed that, is just talk with your pediatrician. I think there's many
ways more often than not that it won't be this diagnosis. But if it is, then
you definitely want to detect it early because there are definitely a lot more
options. Even though we haven't determined the cause of the disease, we have a
lot more treatment options. They just depend on early diagnosis.

Host: And I think as a pediatrician myself, I would say
to patients out there or parents, if you're concerned, if you're not sure what
you're looking at, take a photo of the stool. A photo is worth a thousand
words, and showing that photo to someone really makes it clear what it is
you're looking at.

Marcos Pozo Jatem, MD: Absolutely. A hundred percent
agree.

Host: Well, Dr. Pozo, thank you for sharing your
expertise with us today. If you'd like more information or to refer patients to
Children's of Alabama, visit childrensal.org. That concludes this episode of
Children's of Alabama Peds Cast. If you found this podcast helpful, please
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of Children's of Alabama Peds Cast. I'm your host, Dr. Cori Cross.