PFIC 101 For Kids: An Easy to Understand Overview

PFIC 101 For Kids – An Easy to Understand Overview

SPEAKERS

Tara Kearns, Cedar Ventura, Trey, Emily Ventura, Dr. Jim Squires

 

Emily Ventura  00:00

Oh wow, I’m gonna go ahead and give a brief introduction go over some housekeeping. So if anybody’s using our Wordly translation software, go into the top upper hand upper left hand corner of your screen, you hit live. And then that should open up a new window for the Wordly translation in the top right hand corner. You can hit your language of choice and you will see closed captioning in your language. A few brief disclaimers. The sessions here are set up for information and educational purposes only. So if you have any questions specifically related to you or your child, please consult your physician. Zoom is not a HIPAA compliant platform. So again, in the questions, please leave all patient identifiers out, including name and date of birth.

And then this session is being recorded. It will be housed in the platform for later use, and might be made available on our website at a later date as well. So if anybody has any questions, you can go ahead and ask them in the chat. In this session, we will also allow participants to ask questions via voice. So you can you can use the raise hand feature and if you raise your hand, we can turn on your microphone and you can ask them live. If you’re having trouble with that, then you can go ahead and ask them in the q&a. And Dr. Squires has some very intense moderators who are going to join us. Cedar is going to be one of them. So good luck, Dr. Squires, and I am going to hand it over to you.

 

Cedar Ventura  01:48

What is that anyway?

 

Emily Ventura  01:49

Shhhh. Okay.

 

Dr. Jim Squires  01:52

Emily, thank you so much. For all those attending, thank you. For all those who watch this later, thank you. Again, as I mentioned, my name is Jim Squires. I’m one of the hepatologists in Pittsburgh, who cares for many children with with PFIC. So you know, I was asked to give a talk on PFIC for kid,  kind of aimed towards the younger population. And so recognizing there’s a wide range of what it means to be a kid, from five through 18, depending on how you want to define it.

I went to the liberty of trying to put together some slides that kind of goes through PFIC at a very bare bones level but also recognize that I want to spend maybe the majority of our of our time together answering questions from from those kids who, you know, may have a question that they’ve never asked their doctor or they’ve always wanted to ask, that they always felt they couldn’t ask or from a parent who feels the same way. So I’ll do my best to kind of go through, you know what I think PFIC means for those patients that we can take care of. So I have some slides here. I’m gonna share. Let’s see here…….Share this……. Alright…..Do you guys see the full the full slide?

 

Emily Ventura  03:25

We see it. 

 

Dr. Jim Squires  03:26

Okay, perfect. All right. So again, Jim Squires from Pittsburgh. And you know, the title that I was told to talk about is “What is PFIC?”.  Well, we’ll talk about it. So what’s our plan? What’s the outline? How are we going to do this? Right, so we’re going to first talk about what is the liver, right? Because I think understanding what a liver is, helps a little bit understand what PFIC may be. Then we’re gonna move on to what is PFIC. And then, you know, I just want to briefly talk about how we treat it, and go over some of the ways in which we think treatments may benefit kids with PFIC. So what’s the liver? This is a liver.

This is a picture of your liver. It is a soft, solid organ. It is located right here, in what we call the right upper quadrant of your belly. And, you know, there’s a lot of cool things. I’m not biased in any way, but I think the liver is the most important organ in our body. And it’s got some really cool, interesting facts that I think a lot of people might not know, right?

So first of all, is that it’s mostly what 96% of your liver is water. It’s the largest organ in our body. If you didn’t know that I have a little asterisk there because technically there’s an organ that’s bigger than our liver. But it’s the skin. It’s outside, right. So if you’re thinking about what’s inside the organ and internal organs, which is how we often think about organs, the liver is the largest.

It’s really unique in that it can regenerate. Most of our organs, like your brain and your heart and your kidneys, they can’t really grow back or regenerate if there’s injury to those organs. That injury is kind of, you know, you’re only left with whatever tissues left. You can’t regrow it. But the liver, that can regenerate. So you know, when we talk about liver in the medical field, we use words like hepato, or hepatic. And those are fancy words from Latin that mean liver. So when you hear us talk about hepatology, or hepatitis, or, you know, hepa this, hepa that, we are referring to the liver, and liver related things. And I think, you know, maybe most importantly, below here, the liver doesn’t just do one thing, right.

Unlike the hearts, right, which is just a boring pump, you know, the liver has many, many, many, many, many, many different functions. And so this is kind of like a, you know, a simple Google search picture, if you type “liver function”,  to kind of talk about what the liver actually does. And so you can kind of start at the top right hand side and go all the way around. But, you know, one of the things it does is it prevents shortages of nutrients by storing vitamins and minerals. And so when we eat food and drink stuff, it you know, it ends up going into the liver where we store it for later.

So that if we go through a period where we have to miss dinner, or we skip lunch, the liver is able to kind of break down some of that storage material and keep our bodies going. It produces most of the proteins we need. Now, again, proteins are special, small, biological pieces that make up most of our body, and it makes most of those proteins. It produces bile. And we’re going to come back to this right, about what bile is and why bile is important. One of the things that bile does is it helps us absorb fats, and certain vitamins such as A, D, E and K. It produces most of the substances that we use to clot blood, right.

So if we get a cut, or we fall down, or we get a bruise, and we have some bleeding, the good news is our body knows that that bleeding eventually stops itself. And then we can kind of form a scab. And the way in which blood is able to stop itself is by making proteins in the liver that helps us with blood clotting. It actually helps us fight infection.

So one of the things people don’t realize that the liver does is act as an immune organ, to make cells and to provide an environment for fighting infection. It also metabolizes and breaks down foods, right. So again, we talked about how, you know food that we eat gets absorbed through our intestine, it then goes to the liver and is processed even further. So that it can either be used right away, stored for later, or anything kind of getting rid of certain substances that we don’t need. And that kind of leaves at the top box, which where it removes potential toxic byproducts, right.

So it also acts in a little bit as kind of a wastewater treatment plants to filter out those things the body doesn’t need, and as a mechanism to get rid of it. But again, for the purposes of PFIC, we kind of focused on this unique function of the liver, which is to produce bile, because it is the parts of bile, that that can lead to problems in PFIC

. And so we’re going to talk about that in our next section, which is what is PFIC? Well, first, when we think about PFIC, PFIC is an acronym meaning each of those letters stands for a particular thing, right? And so the P stands for progressive, right. F stands for familial. I stands for intrahepatic. There’s that hepatic word again. And then C stands for cholestasis. But these, these four words in and of themselves are kind of complicated. So we’ll break it down.

 

Tara Kearns  08:24

Excuse me, Dr. Squires

 

Dr. Jim Squires  08:25

 Oh, yeah. 

 

Tara Kearns  08:26

Hi. Hey, sorry to interrupt you. I wanted to let you know. Your screen is a little bit zoomed in. Would you mind zooming it out a little so we can see your entire slide?

 

Dr. Jim Squires  08:37

How do I do that? Oh, my gosh.

 

Tara Kearns  08:40

Oh, that’s perfect. You’ve done it!

 

Dr. Jim Squires  08:43

I’ve done something?

 

Tara Kearns  08:44

Yes. Thank you!

 

Dr. Jim Squires  08:44

Sure! Whatever I did, I’m happy to have helped. Again, we’re kind of walking through PFIC and what it means right? So we, you know, we got to the word “progressive”, right. So what does it mean to be progressive? Well, in medicine, we mean that whatever’s happening is happening gradually, or developing slowly. And so progressive is how we describe that. When we say “familial”, what we mean is that it occurs in family members, and it occurs in family members, because family members share genes, right.

But what are genes? Well, genes are the genetic code or the DNA, probably most of us have heard of DNA, that we get from our parents. And when we have DNA, you know, the DNA that is in our cells undergoes a process called transcription, where it makes this fancy molecule called mRNA. mRNA has been in the news a lot because this is the the material that we’ve used to make a bunch of the COVID vaccines. But the mRNA that’s transcribed from our DNA is then used by the body to make proteins. We already talked a little bit about what proteins are.

But it makes all the different proteins in our body. And proteins are important because depending on which protein we’re talking about, this is where we get the different types of PFIC. I think, you know, depending on who’s in the audience, I think we recognize that there are a number of different types of PFIC. That can also, they can sometimes be grouped together under the umbrella term of PFIC, but these are actually very different sometimes diseases that are due to defects in a particular protein. And so again, “intrahepatic”, this means it occurs inside the liver. And then cholestasis.

So when we talk about cholestasis in medicine, what we’re talking about is a problem with the formation, excretion or flow of bile bile, that substance being that we touched upon before that helps us absorb fats and certain other things. So what is bile, right? And why is bile so important? So bile itself is actually the liquid that our liver makes that gets excreted into our gallbladder, and then out into our intestines. Bile is made of many different things. I think if you look at the bottom, the composition of bile is bile salts, phospholipids or kind of breakdown products that we don’t need, cholesterol. This is how we get rid of cholesterol in our body.

And then bile pigments or bilirubin, which is actually a breakdown product of our red blood cells. And what we use bile for is it in to help with things like digestion, to help with things like absorption of fats, and to help with excretion of some of that nasty byproducts stuff that we don’t need, that gets absorbed from things that we eat from our intestine. But in PFIC, it is the bile salts that we focus in on because it is the bile salts that sometimes can cause a lot of the problems. And bile salts, again, their particular function, right is to help us absorb fats and fat soluble substances.

And so, you know, again, why is this important? Why do we need it? And why does when it goes wrong is it an issue? Well, you know, let’s think about different ways in which we consume fats, right. So you can have a cone of ice cream. You can drink a cup of milk. You can eat a big fatty steak. And all of these things have fat in it, right. And if you look at fat on under a microscope, it kind of looks like this. It’s kind of got a bunch of globules and you know, it’s made up of different kinds of pieces that that kind of congeal together to form what is fat.

Now, the issue with fat, I think we’ve all probably done that experiment in high school, where if you have you know, oil, which is a fat, right, you take a cup of olive oil, and you put it in to a glass of water, it separates out and the oil kind of floats to the top, and the water sits on the bottom because fat and water don’t mix very well.

But as we noted, right, the liver itself is 96% water, and the liver is not unique in that. Most of our body is liquid water. You’ve probably heard that fun fact before. And so in order to absorb fats into our bodies, which are mostly water, we need to break it down into really, really, really tiny pieces and this is where the liver comes in. And this is where the liver makes those bile salts, right, which is this little yellow guy here to help us with this process. Because what bile salts then do is they kind of intermix among these big pieces of fat and they the kind of what we call emulsify the fat or break it down into really itty bitty tiny little fat droplets that we can then absorb across our intestines, which are mostly water.

And so this is why bile salts are so important. If we didn’t have bile salts, all of the nutrition and good things that come from the stuff that we eat, we wouldn’t be able to absorb very well. And so the problem with PFIC is a secretion of bile salts. This is where the one of the main problems and what causes a lot of the symptoms. But why why why is this a problem? This is a problem because you know, every cell in our body is covered by what we call a cell membrane and a cell membrane has two different parts of it. One of which is these little circles, which are actually tiny little fat droplets. And the other are these little pieces on the inside, which are kind of more water like substances.

So if we have a bile salt, which as we just talked about, whose job of a bile salt is to break down fats into tiny pieces, if we have a bile salt, close to, or inside a cell that is unprotected, that bile salts is going to break down the cell membrane, because that’s its job. And so this is again, this is kind of a picture of the different PFICs or at least you know, PFIC 1 through 5, or 1 through 6, and why this is kind of a problem.

And I can come back to this picture, because I know it’s kind of busy. But these little green dots these are your bile salts or bile acids, they’re sometimes called and so it’s this little guy that if we don’t protect against, he can disrupt cell membranes and lead to cell damage. All these different proteins, FIC 1, this is the protein that is affected in those who have PFIC 1. The BSEP is the protein that’s affected PFIC 2.  MDR3 is PFIC 3.  TJP2 is PFIC 4. This FXR over here is PFIC 5 and this MYO5B is PFIC 6. And then as many of us know, there are others.

But all of these different proteins have a role in making sure that as the liver is making bile acids that they are made and get out of the liver without doing damage to the liver cell. And so if you have a defect and one of these proteins, pick which protein, doesn’t matter, you can have a problem protecting the cell against this bile salt. And so that’s where you get the injury inside the liver in PFIC. 

 

Dr. Jim Squires  15:36

So how is it treated? So I unfortunately, we don’t have great treatment options, as I’m sure many on this call know. Oftentimes, we support families and kids where we can, so any complications of their PFIC, whether it’s, you know, having to be on special formulas that allow them to absorb fats, or monitoring for complications of their progressive disease, you know, we support them where we can. We look to optimize their nutrition. So there are certain diets and parts of a diet that we will sometimes put kids on in order to make sure that they are as healthy as possible, despite their PFIC.

As many of you know, itching is one of the terrible complications of PFIC. And so there are medicines that we will try to treat itch and support the itch where we can. You know, as as the name implies, progressive means that these things progress over time. And so it’s one of our jobs to monitor for complications that can develop in diseases that progress. And I think most importantly, is recognizing that there are old medicines and new medicines that we are continuing to try to study and understand how they can potentially help treat kids and adults who have PFIC disorders.

But what happens when none of this works right? I think in many instances, despite all of our best efforts, we aren’t able to really control well, the underlying progressive nature of disease. Well, that’s sometimes then when we call our surgical friends. And our surgeons have a couple things that they’ll try, right. There’s the biliary diversion. And if you’ve ever heard or talked or wondered what a biliary diversion is, these are the pictures. There’s a couple of different ways that we do it. But because we think that it’s the bile that sometimes causes the problem, if we can get the bile outside the body, without being absorbed in the intestine, we have found that that sometimes can help certain people.

And so there’s the external diversion in A, where they actually take a little piece of your intestine and sew it to your gallbladder, which is where bile is stored, and then bring it to the outside of your body. And we put a bag on this and so bile kind of flows outside of the body that way.

There’s something called an internal diversion. We didn’t get into this too much. But this last part of the small intestine here, this is where bile gets kind of reabsorbed into the body, to kind of keep it into the body as much as possible. And so if you bypass this little part of the intestine, the bile, will just kind of go out of your large intestine, and you poop it out. So if you if you do an internal diversion, you can divert bile past the part of the intestine where it gets reabsorbed and so that’s another way. And then this is what we call an ileal exclusion. Ileum being again, this very special part of the intestine, that bile acids are reabsorbed, and if you bypass that, then bile doesn’t get reabsorbed, and you poop it out there, too.

So there’s a couple of different ways that people sometimes will think to get rid of bile. When none of this works, we do liver transplants. And again, some on this call, including my moderator, who I’m trying to slow down by talking, so she has less time to grill me, you know, has had liver transplants for their underlying disorder. And so when all else fails, and when all our other interventions don’t work, we do offer liver transplant sometimes for this disorder. So that is kind of the kind of brief introduction to PFIC. So, hopefully, you know, we’ve finished up by understanding what a liver is and why it’s important, why it’s cool, why people like me study it.

Hopefully, you get a little bit of a better understanding of what PFIC is, why bile acids have a role in PFIC and why we look to treat them in that sense. And again, hopefully we finished up with, as it currently stands, our treatment options. But I’m happy to go through any one or more of these topics on a much more detailed granular level as folks desire for the next 20-30 minutes or so. So I’m gonna stop now. I kind of wanted to go quickly just to kind of, you know, get through the talk, but I really wanted and look forward to the discussion part and welcome any questions that folks may have.

I’m gonna stop sharing and go back to the picture. I see Cedar ready with questions. I see we got a couple in the chat already. So alright Cedar, what do you got for me? Let’s do it.

 

Tara Kearns  19:53

All right.

 

Cedar Ventura  19:55

So I have two questions. 

 

Dr. Jim Squires  19:57

Okay. 

 

Cedar Ventura  19:58

This one is what happens when….well, basically when they do a liver transplant?

 

Dr. Jim Squires  20:06

Well, so I think, again, Cedar’s question is “What happens when they do a liver transplant?” Well, one of the things we know about PFIC is that that protein…..and I should say in most PFICs, that protein that is defective is inside the liver. It’s all in your liver. And so when the liver gets injured to the point where it’s not working very well, again all those 200 functions we talked about, that the liver isn’t able to do those functions very well, we have complications.

When they do a liver transplant, they essentially will go in and take out the liver. And they will kind of tie off, you know, the blood that’s coming into the liver and the blood that’s exiting the liver. They take out your organ, and they put a new one in. Put, you know, tie the vessels that feed the liver back together, tie the vessels that empty the liver back together, and then you have a new liver.

I think one of the great things about liver and liver transplant is that as opposed to many other organs, the liver tolerates that really well. You know, some other organs, it’s a lot harder to perform transplants. Because whenever you have a liver transplant, you know that liver that is now inside you wasn’t yours originally, right? It was somebody else’s, or part of somebody else’s. And so whenever you have something inside your body that isn’t yours, sometimes the body fights that off with immune cells and with other kinds of mechanisms that it usually is using to protect you.

And so when you get a liver transplant, we often give you medicines that you have to take every day to kind of keep your immune system a little bit at bay, so that it kind of accepts that new organ that’s inside you. So that’s what they do. They essentially just cut out your old liver, put it in a new one.

 

Cedar Ventura  21:49

Thank you for that.

 

Dr. Jim Squires  21:50

You’re so welcome. What other questions we got?

 

Tara Kearns  21:56

All right. So moderator Cedar, you said you had two questions. What your what is your second question?

 

Cedar Ventura  22:07

My second question was….you kind of explained this in the beginning, but just a little farther, what is bile, basically?

 

Dr. Jim Squires  22:17

Yeah, no. So again, bile, it’s a really complex substance, right. And it has, so it’s a mixture of a lot of different things. You know, but but it’s a combination of breakdown products. So you know, if you think about what is bile, and where’s it come from? Bile is, is if we went to back to that picture of the liver, bile is also how our liver gets rid of a lot of stuff we don’t need. So part of what bile is kind of waste products of kind of things that our body has been, you know, it’s done using, so it needs to get rid of it. And so, you know, bile is used to get rid of that.

Bile has, you know, kind of cholesterol, which are parts of fats that we take in. And then bile has these things called bile salts, which are those products that we, you know, we went over, that kind of helps us break down the big fat globules that we eat. And again, it’s the bile salts in PFIC that end up causing the problem, because all of those different proteins that we use to make bile salts and make sure that bile salts get out of our liver and where they need to go safely, those are defective in PFIC. When we can’t get those bile salts where they need to be in a safe way, those bile salts can injure the liver.

So that’s that’s the challenge. And this is why again, for those on the call, you know why why was there used to be just three PFICs and now there’s six. I was on a talk yesterday where he identified 12 potential PFICs. You know, we learn more and more about PFIC because PFIC, you know, there’s lots of different proteins that are involved in making bile and making sure it gets added to the liver in a safe way. And the more proteins that we understand help with that process, the more chances we can identify when one of those doesn’t work very well, that can cause disease. Does that makes sense?

 

Cedar Ventura  24:05

Yeah, that makes sense. 

 

Dr. Jim Squires  24:07

I’ll give you another fun fact. So bile also contains the stuff that gives our poop its color. If you don’t have bile, or you have like a blockage of bile, your poop is like, white. So yeah, I know. So people who have white poop have like a whole nother problem right. But if you if you ever noticed you have white poop, call your doctor. Tell your parents. We want to know about that. But that’s not that doesn’t generally happen in kids with PFIC.

 

Cedar Ventura  24:39

Thank you for that explanation.

 

Dr. Jim Squires  24:41

Sure. Sure. Trey, you got any questions? I see you down there. 

 

Trey  24:48

Yeah, um, so how’s PFIC affect you?

 

Dr. Jim Squires  24:53

So again, I mean, PFIC affects everybody a little bit differently. And this is one of the really big challenges that we have because PFIC is what you know, you know, like I said, yeah, let’s say you take the color white and the color black, right? Then there’s like a million different shades of gray in between those two ends of the color spectrum. And PFIC is kind of like that. There are people who have really bad PFIC, whose livers get sick very, very early and sometimes need transplant at a very young age. And there’s other people who we say have PFIC, or at least have have the same protein, that doesn’t work very well, but who may only have intermittent problems and do quite well.

So this has always been one of the challenges of trying to kind of define or give a good definition for PFIC. And so in when someone says, “Well how does PFIC affect your liver?”, you know, a lot of times that depends on the individual patient, right.  Because what may be your experience with PFIC, Trey, may not have been Cedar’s experience with her PFIC, even though we’re saying you have the same thing, right. And so I think that everybody is a little bit different. And so we always have to try to be very careful to recognize that each kid is very unique. Although we sometimes try to say “This is all the same disease”, they’re very different, or at least they can they can present very differently in individual kids.

 

Tara Kearns  26:26

Well, that’s a really great answer, Dr. Squires. Thank you for that. 

 

Dr. Jim Squires  26:30

Sure

 

Tara Kearns  26:30

But another question, what happens…is it possible after transplant to be itchy again?

 

Dr. Jim Squires  26:38

Yeah, so the short answer is yes. You know, the one that we worry a little bit more about that in is PFIC 2, because PFIC 2 is unique in that PFIC 2 can actually recur in a liver transplant, in someone who’s had a liver transplant. The reason that happens is it’s pretty complex, actually. But most other PFICs, if they’ve had a liver transplant, no longer itch. Their new liver is able to make bile safely, get the bile out safely and so they don’t have any problems with itching after their transplant.

Sometimes there’s other complications that we have to watch for. And so we never, you know, we’re always trying to balance, you know, whether or not transplant is going to be the right intervention for an individual patient. But after transplant, you know, unless you have PFIC 2, we generally say you’re not going to itch and even if you do have PFIC 2, the chances are your itch is going to be eliminated for good.

 

Tara Kearns  27:43

Okay, so another question. So, our kiddos with PFIC, as you can see, you know, we’re pretty few in numbers. You know, and for most of our kids, they have only ever met a few kids with PFIC and it’s been through this conference experience. So can you let us know Dr. Squires, how many kids with PFIC have you ever met?

 

Dr. Jim Squires  28:14

Hmmm. I have met a lot of kids with PFIC, actually. And you know, part of that is kind of based on on where I am in the country and that I’m in Pennsylvania, and Pennsylvania has a group of people called the Amish and Mennonites where where…. sometimes people will will hear PFIC 1 be called Byler’s disease. Anybody ever heard that term? Cedar… Emily…err…Cedar’s never heard of it? Trey, ever heard of Byler’s disease? Not Trey either. But Byler’s disease is actually named after a family whose last name was Byler, that was their last name. And the Bylers are from Pennsylvania, the middle of Pennsylvania. And these, this family of Bylers, they have lots of members and so we see a lot of people who come from this small community where PFIC is a little bit more common.

But you know, you are right in that at the end of the day, PFIC is still in most…. you may talk to many liver doctors who’ve never seen a patient with PFIC, particularly somebody who may not be at a large center. So these are still what we call rare diseases. They are not common. And you guys are very, very, very unique. Which we recognize also sometimes leads to some of the frustrations as a patient and as a parent.

When you’re trying to talk to your doctor and your doctor is like actively Googling, you know, “What is PFIC?”, right, you know, or “How do I treat this? I’ve never heard of this. I think I read about it once in a textbook.” You know and so, that that that is a real experience that we recognize and you know, this is where you guys have done such a great job of getting the word out right to the community, you know.

Everything is power in numbers. So Cedar, Trey, thank you guys for lending a voice and a face to these rare diseases because there’s, there are lots of other kids out there that kind of need you guys to help them be their voice where you can. But it is rare. I have seen a lot of kids with it. You know, and I think part of that’s uniquely for where I am and I’m in a large institution where a lot of kids kind of get referred to. So

 

Tara Kearns  30:30

Yeah, well, thank you. So guys, it’s good to know that there are lots more kiddos out there just like you guys, even if you might not cross paths with them. It’s nice to know that you guys are not alone. So I think Trey, from our audience

 

Dr. Jim Squires  31:08

Did you have a question, Trey?

 

Tara Kearns  31:09

Do you see the question Trey, from the audience?

 

Trey  31:14

The question is, if you get a transplant doesn’t last your whole life, or will you need more?

 

Dr. Jim Squires  31:19

That is a great question. And you know it as with all questions, it can be complicated. We generally hope and plan that if you need a liver transplant, that that transplant will last you your whole life. Now, the longer answer to that is that we still are learning about transplant, because transplants in kind of it’s in the modern era of transplant, right or, you know, kind of in its newest form is really only about, you know, 20 to 25 years old.

You know, the first liver transplant was done in 1960. But you know, liver transplants with any kind of, you know, larger numbers really didn’t start till the 80s. And it really wasn’t until the late 90s, early 2000s, where we had the knowledge in the medicines that allowed us to treat transplant more effectively. And we’re learning more each day right. Transplants today is different than it was 20 years ago. But when we talk to so so the answer there is, you know, if you’d asked me what is the liver transplant look like 60 years from now, we just don’t know. Because, you know, for the most part, we only really have 20 to 25 years of information that can allow us to kind of inform that answer and tell you what what it means.

Now, the numbers there are that about 85 to 90% of people are doing really well after their transplant that far out. But the challenge there is obviously for you know, our kids who are, you know, 5, 10, 15 years old when they get their liver transplant, you know, 25 years is that gets to, now they’re 30. Okay, so that’s not a whole life, but we just don’t know, right. Well, there are, are only very, very, very few people who got transplanted, you know, in 1980, that we’re able to kind of understand if that’s going to be the experience of everybody, or just that kind of one patient.

So it’s hard. But we can say that, you know, in general 20 to 25 years out, transplants are really well. There are some times where the liver transplant doesn’t do as well. And there’s a variety of different reasons why that happens. And there are patients who sometimes need a second liver transplant for, again, a variety of different reasons that I’m happy to talk about. But when that happens, you know, we can we can visit and we do repeat transplants when when they’re needed.

 

Tara Kearns  33:57

Thank you, Dr. Squires, I think Cedar…do you have another question?

 

Cedar Ventura  34:02

Um, yeah, so I have two questions again. My first question is, how does like certain foods affect like the medicines?

 

Dr. Jim Squires  34:14

It’s great question. So you know, we don’t really think that certain foods affect your medicine or affect your PFIC. There are certain foods that depending on how sick your liver is, you may not be able to tolerate very well or absorbed very well, you know. So if you have a PFIC where your livers very sick, or that bile isn’t able to flow very well, you know, sometimes you’re not able to absorb those fats that we talked about. And you know, as much as we talked about how bad fat is for you, at the end of the day, you still need fat to do many, many different things.

And so absorbing fat is a good thing and when you can’t do that, sometimes, you know, kids can not grow very well. They can be kind of on the small side. Um, sometimes there’s those vitamins that we talked about the Vitamin A, Vitamin D, Vitamin K, Vitamin E, you know. Those are really important vitamins and if we can’t absorb those very well from our fat, sometimes if we get deficient in those, there can be complications from kind of low vitamin levels. But, you know, generally, if you pick, you know, unless unless you’re a baby, that sometimes there’s special formulas we may we may put kids on, there’s no restriction that we would say that you need to know foods that are going to make you any sicker.

 

Cedar Ventura  35:37

Um, well, then my second question was, Trey might already have asked this but what is the difference between PFIC 1, PFIC 2 and PFIC 3?

 

Dr. Jim Squires  35:49

That’s a great question. So again, the different types of PFIC are based on the protein that is defective in those disorders. And so, you know, I think I shared that one cartoon of all the different, you know, that kind of like the pathway, right? Because there are many, many, many different proteins whose job it is, is to get make bile and then get it out of the liver safely. Right. So I guess you could kind of think about it, like, you know, like a car, right? You know, if you have a car that’s supposed to drive down the road, there are many ways there are many reasons why a car might not go down the road well, right. Like if I came in stole all the tires off your car, well, the car wouldn’t work very well, right. So maybe that’s PFIC 1.

If somebody else came and took the engine out, but left the tires, well guess what the car is still not going to work. But there’s a whole different reason why that car is not working, right, because the engine is gone. And somebody else came to cut the gas line. And so part of it is recognizing that like a car, there’s a lot of things that go into making a car drive well, right, and get you from your house to Trey’s house.

But there’s a lot of different reasons why that car may not be able to get you to Trey’s house. And so depending on which part of the car is defective, you know, that’s where we label the different PFICs. So they’re all trying to do the same thing. But they all have to work together to do it correctly and just taking away one piece sometimes can lead to a lot of trouble. And so that’s where the different PFIC numbers come in.

 

Cedar Ventura  37:25

So you’re saying like different stuff causes each PFIC?

 

Dr. Jim Squires  37:31

Exactly right. There’s a different, you know, unique problem that causes each PFIC. Even though at the end of the day, sometimes what you see in a patient is very similar, right. So again, going back to the car, you know, the story, you know, at the end of the day, the car can’t drive, you know, but but sometimes there’s there’s a lot of different reasons why that car isn’t driving. And it’s based on, you know, again, in PFIC, it’s based on very specific proteins, whose job it is to perform a certain function to get that bile out safely.

 

Cedar Ventura  38:05

Ah, and I just actually thought of another question I was going to ask. So when he said… Trey said, like, Can itching affect after the transplant? Why is that only with PFIC 2?

 

Dr. Jim Squires  38:26

Yeah, so again, this is like, you know, and I’ll take a step back, say like, it’s really rare, right. I mean, like, we would not do transplants and expect your itch to come back. But, every now and then PFIC 2 is special, in that, you know, we talked about how your body you know, the immune system of your body sometimes can recognize things that aren’t your own right and attack that.

There is a very unique problem in PFIC 2 where the body will recognize that one protein whose job it is is to is to to get the bile salts out and will attack just that one protein. Like just that, it won’t attack anything else about your new liver, just that one protein. And so you know, let’s let’s like go back to our car analogy here right. So let’s say that PFIC 2 was a problem with the tires right and you know that that for whatever reason the tires just like kept kept getting flat over and over and over again, right? Well, we’re going to put new tires on and so now you got new tires, and they seem to be working okay, but then all of a sudden, the tires are getting flat again.

So it’s kind of like the same problem recurs but it’s in a new liver. And it it’s, it’s a complication of your immune system, but it’s one that’s kind of unique to PFIC 2. The good news is now that we know that that’s a possibility, I think early on, it kind of stumped us when it happened, like you know. But now that we know that it’s a real possibility, we watch for it. And if we’re seeing signs of it, we have treatments we can give that stop it. So it’s becoming even less of a problem now because we’re able to prevent it. Does that makes sense?

 

Cedar Ventura  40:14

 Yeah.

 

Tara Kearns  40:16

Really good question, Cedar.

 

Tara Kearns  40:20

Dr. Squires, I really love your illustration with the car. I think that is probably the easiest way I’ve ever heard it broken down why…how all of these different kinds of PFIC are related yet different. So, so you know, because this session is mostly for school aged children, we want to ask a question related to school. Some of our students, some of our participants, they are in school, some are homeschooled. So we have a couple different questions about school. So if you had to pick maybe two things, what do you think are the two most important things that PFIC kids and their families can communicate to their schools about their disease?

 

Dr. Jim Squires  41:13

Man, that is a great question. And again, it part of it depends on you know, the individual kid and the symptoms they’re having right. So for somebody, maybe the most important thing is that, you know, you know, that I that my liver disease, you know, has that sometimes I you know, maybe my eyes can be a little bit yellow, or maybe my belly can look a little bit big, you know, or maybe I get tired easily than other kids. Or maybe again, I have a lot of itching and so sometimes I’ll have some scratches on my arms, and I need to take a medicine or do creams. You know, and so I think that it’s, it’s a kind of a very individualized patient question. Right.

But but I think at the end of the day, you know, one of the things that I would try to stress most is that, you know, you can tell people that you have a sick liver, but you know, that it doesn’t define you, right. That that’s not going to be who you are. It’s just part of you. But that sometimes you need to take medicines, and sometimes you need to have a little bit of a slower day. But but that, you know, the that hopefully, the liver disease isn’t going to be what people know you for. They’ll know you for, you know, your incredible personality or your funny jokes, or your skills on the basketball court, right or your math ability. I was never known for my math ability. Nobody ever knew me for my math ability.

And so that’s what I would kind of, you know, that’s what I would try to focus on, is that, you know, you know, if you need, if you need from a medical standpoint, from a doctor standpoint, you know, a, you know, a little bit more time to take a test, or a reason maybe to not necessarily, you know, participate in some of the physical activity stuff, you know, that you need, then we can do that. But that there’s other things that are going to be better to define you than a sick liver.

 

Tara Kearns  43:18

Thank you. And so another question for our, our up and coming PFIC kiddos like Cedar and Trey, who have a lot to say about PFIC and some of our participants that are on the line here. I know Cadence is here. And they’re all very interested in learning more about this disease and then taking action. So for those kiddos that are interested in the medical field, can you tell us a little bit about how you became a doctor working with PFIC or maybe some things that they need to remember when they’re in school? Because you said you you weren’t really great at math, so how did you, what’s….I guess what classes are the most important or what can they think about if they want to, you know, be a PFIC doctor like you are?

 

Dr. Jim Squires  44:12

Yeah, so I mean, I guess what I would say there is, you know, you should, there are a million different paths to being whatever you want to be. And I have friends that are doctors that studied English, and I am married to a doctor who studied economics and Spanish and I have friends that are engineers that studied biology. And so you know, I’ve always found that if you ask somebody, you know, “Why did why do you do what you do? What is it that made you want to do that?”, generally, what they point to is somebody along the way in their life, who they looked at and said, “That’s awesome. I kind of want to do that”, you know.

But that that, you know, the to get there, you know, you need to come do the things that interest you. Because, you know, if you really, really, really dislike, you know, drawing, yeah, you’re just like, you’re not very good at it. It’s hard, it’s challenging, you know, then then you’re not gonna want to take those classes.

But I think I became a doctor because I knew some folks that were doctors that I thought, you know, when they spoke, they spoke like they really loved their job. That seemed really fun. They felt like they were always learning something. But I really don’t…again, I don’t think that that’s not unique to medicine at all. Right, I mean, I think really any profession that you’d want to do, and I would stress this by saying, as a PFIC patient, you can do whatever you want.

There is no restriction on any sort of job that you’d ever want to have. But you got to kind of, you know, keep your eyes open for those people that you come across in life that you kind of feel like, are happy and are happy because they like what they do, and like getting up and doing what they do. And recognizing that there’s a lot of people who have very, very different jobs who have that same experience. If anybody ever wanted to learn more about what it’s like to be a doctor and go to med school, and all that stuff, yeah, I’m happy to talk to you whenever and for however long. I do love my job. And I think it’s fascinating. And most of the like, you know, these these kids, you know, I think they’re, they’re pretty awesome. They’re pretty inspirational.

But I think that, you know, you can be impactful and you can be important. And you can love what you do, whether you’re a teacher or a nurse or a doctor or a lawyer, or an engineer, or an artist or any number of things. And they’re all amazing jobs.

 

Tara Kearns  46:52

Thank you so much for taking the time to explain that and give our kiddos some inspiration. So as we get close to time here, I want to just ask any of our kiddos listening at home, if anybody has any additional questions, go ahead and put them in the chat or ask a parent to help you type it in the chat. So I know you guys have asked a lot if you guys have any last burning questions. Now’s the time

 

Dr. Jim Squires  47:23

This is  like “Stump The Doctor” time. It doesn’t even have to be about PFIC. You can ask me about like, you know, anything. Anything out there, kike what’s my favorite color? Green. Green is my favorite color.

 

Tara Kearns  47:38

Green is your favorite color? What’s your favorite…do you like sports Dr. Squires?

 

Dr. Jim Squires  47:43

Oh, I do like sports. Yeah. No, Emily’s not allowed to ask questions. No, this is not fair.

 

Cedar Ventura  47:50

Awww

 

Tara Kearns  47:51

What’s your favorite sport to watch Dr. Squires?

 

Dr. Jim Squires  47:54

You know, my favorite sport used to be basketball, but I now have kids who really like soccer. And so I’ve gotten yeah, I’ve gotten into watching soccer because my kids are into watching soccer. And I never watched soccer growing up and I’ve learned a lot about it. Pretty fascinating sport.

 

Tara Kearns  48:10

Wow. We’ve got a lot of we’ve got some sports fans. Trey is a big sports fan.

 

Dr. Jim Squires  48:17

What do you like Trey?

 

Trey  48:21

Football and baseball

 

Dr. Jim Squires  48:23

Football and baseball? Who’s your football team? 

 

Trey  48:27

Ravens

 

Dr. Jim Squires  48:28

 Ravens? Come on, man! You know, I mean, I’m in Pittsburgh. You can’t…. I can’t…alright, well, we’re gonna mute Trey. Trey won’t be able to talk anymore for the rest of this talk. Cedar, what do you got? You got something?

 

Cedar Ventura  48:45

Yes. So what was my question? Oh, yeah. So this might be a tricky question. 

 

Dr. Jim Squires  48:59

I’m ready. 

 

Cedar Ventura  49:00

How do they transport the bad liver and then put the new liver and like all of that stuff?

 

Dr. Jim Squires  49:07

How do they transport it? Well, I mean, yeah, so this is actually easy, right. It’s like the same way you transport like, your soft drinks to a football game. You put it in a cooler, on ice. And you just carry it with your cooler, from one hospital to another. And it’s as easy as that. So if you have a bag of ice and an Igloo cooler, you could transport organs. Yeah I know! You’re telling me.

 

Cedar Ventura  49:41

Wow

 

Dr. Jim Squires  49:45

 I mean, we keep it cleaner. You know, we do other things. But you know, it’s not that it’s you know, it’s not that subspecialized. You just need a cold, cold space and cool, something to keep it cold.

 

Cedar Ventura  49:59

Yeah, I have one more question,

 

Tara Kearns  50:00

What do you do with the old? What do you do with the old livers?

 

Dr. Jim Squires  50:05

Well, you know, this actually…. so old PFIC livers, we got throw out. They don’t, they don’t work for anybody. There’s not a lot we can do with those. Sometimes we save a piece and then you know, we can have, you know, we bring patients down if they want to see the old livers like, you know, under a microscope or stuff. Sometimes patients allow us to do research on old livers, right? Again, we there’s a lot about PFIC, we don’t fully understand. So if we can take a piece of it and like, you know, do a bunch of experiments on it to understand a little bit more about what PFIC is and what it does.

There are some disorders and this is where I can kind of geek out a little bit, so I apologize, where you know, they may have a sick liver, because you know, they have one protein that’s missing, but other people don’t have that. For that protein is not just in the liver. So we can actually take their livers and put it into somebody else. And that’s called the domino transplant. So I’ll take one liver from a donor, put it into a patient, the patient’s liver and put it into somebody else. And that’s kind of cool. So that can happen.

 

Tara Kearns  51:01

Okay, that does sound cool. Go ahead, Cedar. You can you can, you can help us end our session with the last question. Okay.

 

Cedar Ventura  51:09

This is a question I have been thinking about for a long time. Um, what tools do they use to do the transplant?

 

Dr. Jim Squires  51:19

What tools do they use us to transplant? They have lots and lots and lots of really cool tools. Sometimes it’s as simple as a scalpel, right. We all know about the knife. But you know, today, they don’t really even use scalpel as much anymore. It’s like a..it’s called an argon beam. It’s a laser beam. It is literally like, yeah, it’s like a laser, it shoots a laser. So they use these laser beams. And then a lot of times it’s kind of old fashioned needle and thread. So they use you know, needles and they kind of sew stuff together just like somebody would sew, a,  you know, a ripped sleeve onto a shirt or something. So it’s it’s pretty but yeah, they’re working really really tiny so they got big glasses that they use so they can see these little tiny spaces.

 

Tara Kearns  52:05

That’s really cool to think about.

 

Dr. Jim Squires  52:09

 Laser beams and needles

 

Cedar Ventura  52:10

Thank you.

 

Tara Kearns  52:13

Cool. Well Dr. Squires thank you so much for doing this presentation for our kiddos. We’ve got some comments in the chat that this was great and easy to understand. So thank you there’s definitely some nuggets here that we will take away and it’ll help us when we try to communicate to friends and family and other kiddos about PFIC. So thank you so much for your time this was terrific.

 

Dr. Jim Squires  52:42

Absolutely anytime guys. Great seeing you. I think I think I’m on a panelists session tomorrow too with everybody else, all the other talkers, so I’m sure we’ll see you there. Except for Cedar’s not allowed and Trey is definitely not allowed. No Ravens fans. We don’t accept that haha.

 

Emily Ventura  52:57

Sorry. Haha. Okay, thank you so much Dr. Squires, and to all of our participants.

 

Cedar Ventura  53:04

Bye!

 

Tara Kearns  53:05

We’ll close out this this webinar and oh….haha. Trey is showing you his Raven shirt. 

 

Dr. Jim Squires  53:12

Ha I got that

 

Tara Kearns  53:14

We will see you guys back at the two o’clock session that’s going to be led by Cedar and Cadence and Trey so don’t miss out on a time for our kids to connect. So thank you again and we will see you guys shortly.

 

Cedar Ventura  53:29

Bye bye