Transcription:
Abnormal Liver Labs in Children

Melanie Cole (Host): Many diseases and conditions can contribute to elevated liver enzymes. Because the liver is so complex, it’s susceptible to a wide variety of adverse effects. My guest today is Dr. Yumi Turmelle. She’s a Washington University pediatric gastroenterologist and the medical director of the St. Louis Children’s Hospital Liver Care and Transplant Center. Welcome to the show, Dr. Turmelle. Explain a little bit about the function of a normal liver for us to begin.

Dr. Yumirle (Yumi) Turmelle, MD (Guest): Hi Melanie. Thanks for having me on the show today. Yes, so the liver is one of the most vital organs in the body. You probably cannot live with it for more than maybe 24, 48 hours without it. It has some really important functions. For example, it synthesizes proteins. The two most common proteins it synthesizes is albumin and clotting factors which are very important to maintain both clotting in your body and your fluids in your vascular spaces. But it does many other things. For example, it stores carbohydrates and amino acids for when the body needs it, and importantly it also detoxifies the bloodstream via biliary excretion. So, this is important for drugs and toxin metabolism. It gets rid of the bilirubin from the body – the breakdown of red blood cells and it gets rid of cholesterol and lipids and changes it to other forms needed for the body. So, it’s the main – one of the main digestive organs of the body because it produces bile, and bile is important to emulsify and absorb fat from the diet. So, if you’re jaundiced or have cholestasis or elevated bilirubin and the bilirubin is not getting into your intestines, then you have trouble absorbing the fat, and you’ll see – especially for us in children -- we see children start to have problems with weight gain and failure to thrive.

Melanie: So tell us about some common liver diseases or some conditions and factors that can lead to liver issues in children.

Dr. Turmelle: So, as you can imagine, there's a wide variation of conditions that affect children’s liver, and some of them are sort of distributed by age. So when we first look at a child, we look at their age, and we think of the most likely etiologies for the condition, and we look at what type of injury is going on in the liver. So, for example, we know that the transaminases, your AST and ALT, we always have a detectable level that runs somewhere between 20 and 40 microliters per liter in our body because we always have a turnover of liver cells, so, but when that number starts to rise, greater than like 1.5 to 2 times the normal level, that’s when we start to worry about that there’s liver injury going on.
So, I want to make it clear that there’s two things that we sort of look at when we’re looking at a patient that we worry about liver disease. One, is liver injury, and liver injury is measured as we talked about with the transaminases – are they elevated? But liver injury – those numbers – just tell us that there’s some injury going on, but it doesn’t tell us how the liver is functioning, which is very important. So, then we have to look at other markers to see how the liver’s functioning, and for those we look at the bilirubin. You know, if the liver is functioning like it’s supposed to and excreting the bile; if not, your bilirubin is elevated, and is your liver making the proteins we talked about? You know, the albumin level and the clotting factors because you could have liver injury -- and we’ll talk a little bit about liver injury – and then you have liver dysfunction which is more dangerous. More concerning is the liver dysfunction – that the liver’s having trouble doing what it's supposed to do.

Melanie: So when we’re talking about clinical presentation – you know as you're going to tell us about the tools and to aid in early diagnosis of abnormal liver function. First of all who would notice something going on with a child that would even send them for labs for their liver function? Would that be the pediatrician, would that be the parent? What would they notice?

Dr. Turmelle: So, there's a wide variation of presentation. Some are asymptomatic where patients get picked up completely as part of routine. They’re going for their yearly visit, or a sports physical, or part of, you know, some guidelines recommended by American Board of Pediatrics. If your weight is a little bit higher and then those are detected, the elevated enzymes are detected, but the patient doesn’t have any clinical symptoms. They’re otherwise healthy children running around. So, that’s one. Those are the asymptomatic.
And then there’s patients who are symptomatic. So, these are patients that have symptoms, and the symptoms could vary from an acute presentation to a chronic presentation. So, an acute presentation is the child that was completely normal, you know, just a few days ago then all of a sudden turns jaundiced or is very fatigued or starts bruising or nose bleeds, you know, or have changes in mentation in terms of – sometimes they develop; we’ll talk a little bit about it – hepatic encephalopathy, or they develop ascites, which is fluid in the belly. You know, so all of a sudden they went from sort of well children to very sick children in the matter of days, and I'll speak about it a little bit later, but one condition that’s very dangerous is acute liver failure. That means that the liver is failing, and it's failing very quickly, and many of those patients die without a transplant. So, that’s something to be very concerned about and monitor very closely.
And then there’s the patient who gets picked up as part of just sort of chronic symptoms, you know? They’ve been tired for a while. They are not growing well. They might have some paler stool because the bile’s not getting to the intestine. The pediatrician notices on their exam, or the parent, that they have a bigger belly, and they feel some hard organs in there. So there’s different ways to pick up children. But I would say the majority is usually – it's very obvious when there's an acute presentation, but the other, the asymptomatic, and the chronic are a little bit more difficult, and that’s why it's so important to have a yearly exam with your pediatrician because the pediatrician is not only, you know, taking the history, but also examining the patient, and sometimes there's no sort of sign, like physical signs or clinical symptoms that the patient’s describing, but then they feel they're dying, and they realize, ooh, there's a large organ here. The liver, the spleen – and that’s important because once they're large organs, that means it’s been going on for a while.

Melanie: So then speak about your approach to the patient with abnormal liver biochemical and function tests. Speak about those tests a little bit – what might you run and then what are some current issues in medical management once you’ve assessed what's going on?

Dr. Turmelle: So, yeah, so the approach, as we talked, depends on the age and the most likely diagnosis, but what I think is important is that, you know, we are available to speak to any pediatrician at any time, and sometimes it's difficult to interpret liver labs. So we will be happy to help them interpret liver labs, and sometimes it's as simple as, you know, they had a little hemolysis during the blood stick so the ALT and AST are a little elevated because they're also found in tissue outside the liver like red blood cells. So, you know, if they see it’s a little bit elevated, by the simple phone call, say, hey, why don’t you just repeat it in you know two weeks and let’s see where it is. The other thing that we have to be careful – we get a lot of calls and referrals – is sometimes there are different baseline normals for children than adults. So, when the pediatrician sends a child to a lab that mostly does adults, they're using their normal values, and the children’s normal values might appear abnormal in that setting. So, they come to our hospital where the child’s age determines the normal range they’re using, and then their liver enzymes are normal. So, sometimes it's just as easy as repeating the enzymes to make sure because remember, liver enzymes come from many other sources besides the liver. So, they come from muscle, and they come from brain and heart and kidneys, and like we said the red blood cells. So, sometimes maybe with a little injury, as the blood draw we talked about, or maybe they had a little virus, and they were elevated, but that doesn’t mean that they have ongoing liver injury. So, it's important to determine if this is just a one-time transient elevation of enzymes or if it's persistent, and persistent makes your worry that there is something going on with the liver. So, that’s when we talk about, you know, we usually monitor the labs for about a month or two, and as long as the other numbers we talked about – the synthetics are just stable – we feel comfortable just monitoring the enzymes to see what happened over two or four weeks. The trend will tell us a lot. If you know they were sick and the trend is they're returning to normal, and by four weeks they’re completely normal, then sometimes we never know what happened, but it could have been a little virus they had or maybe some other injury like they took an antibiotic. So, it all depends. What we worry about and what we want to have early referral to our center is the patients who we think have sort of an acute presentation of liver illness – especially dysfunction – and the chronic patient because it's important to diagnose them, and diagnosing them – sometimes the timing is critical – and one example that I want to really dive into is biliary atresia, and the reason we talk about biliary atresia is because biliary atresia remains the number one indication for liver transplant. So, you know, in the United States, we do close to 400 liver transplants in children a year, and about 40% of those are because of biliary atresia, and biliary atresia is a condition that we still don’t know the etiology, but it presents very early on neonates in terms of within the first two months of life. So for any pediatrician who’s seen children as part of their general well checkups, in the first two weeks, if they’re jaundiced, we really recommend that they fractionate the bilirubin to see if it’s all this sort of indirect bilirubin which is part of like the breastfeeding jaundice, or just sort of newborn jaundice, or is there something more concerning? Is it direct bilirubin? That means there is something going on with the liver because those kids need prompt evaluation because we have an intervention, and the intervention is a procedure. It’s a bridging procedure, a surgery called the Kasai procedure, but we know that the earlier that procedure is done, the better the outcomes of the children in terms of long-term survival and need for liver transplant. So, I know we all know the American Pediatrics Guidelines that by 3 weeks of age, if the baby’s still jaundiced, you need to fractionate the bili, but I would say, yes, please follow that recommendation, but even by two weeks of age, especially if it's not a breastfed baby, like if it was a formula-fed baby, fractionate that bili. Make sure it's safe. Make sure there’s nothing concerning with the liver.
So, Melanie, going back to your question, you know, our approach is we, you know, we see the patient, and, you know, especially with patients with liver disease because we know they could get sick and deteriorate very quickly. We have a policy that we can see any child within 24 hours, and you know, and sometimes it's just easier for us to see the patient and do the labs and imaging here than the pediatrician starting on the outside because we have to track the labs down. Some other laboratory places where the labs get drawn – don’t do it there; send it out, and it takes a few days and then the most issue we have is imaging. Like if you get an ultrasound done locally, the ultrasound sometimes is not even done by a pediatric radiologist who knows how to read children’s ultrasounds and that’s difficult because they, you know, like the results of the ultrasound are very dependent, very subjective on who’s reading the ultrasound. So, sometimes we unfortunately have to, when the patient comes to us, we have to repeat a lot of the images here. So, we rather just, you know, in terms of overall expediting the process, and it’s also saving the patient some cost, is just bringing them here and doing the full evaluation here, if that makes sense.

Melanie: It certainly does and what great information and to wrap up, in summary, doctor, please tell other physicians what you'd like them to know about abnormal liver labs in children and when to refer.

Dr. Turmelle: So, I think the key point is if you detect an abnormal either liver lab in terms of the transaminases, the AST and ALT, and it's the first time that you’ve ever noticed this on a patient, have them recheck. Recheck them in a few days because the half-life of these enzymes are only 24 to 48 hours. So, if it was something that was transient, then they should be better within the next few days. If they persistently stay elevated, then that’s more concerning. That’s the type of patient that you should refer to a hepatologist so we could evaluate the patient. Second, if in your evaluation of a patient you noticed any type of liver dysfunction in terms of jaundice or low albumin or increased PT/INR, or symptoms that correlate with liver dysfunction, such as, you know, the jaundice, the clotting issues, the bleeding. Then those children – we don’t know if this is something chronic or this is an acute presentation of liver failure, and that as we talked about, is very dangerous. So, those patients for sure, quick access to a hepatologist. With acute liver failure, you also want to have a patient sent to a center like ours that does liver transplants because, like we talked about, about half of them will require a liver transplant, and it happens really quickly if their liver is going to fail within a few days, and you want the family to be prepared and have the best chance for that patient to survive, and the last thing is, we talked about the babies. The babies are very important. So, if you have a baby who you're seeing, you know, after the hospital discharge, you're seeing in your clinic and it's still, you know, two to three weeks out or a month out and there's still jaundice – just fractionate that bili. Make sure that it's all safe because like we talked about, the promptness of the diagnosis for biliary atresia really makes a difference in their outcome.

Melanie: Thank you so much, Dr. Turmelle for being with us. It’s really great information. A physician can refer a patient by calling Children's Direct Physician Access Line at 1-800-678-HELP. That's 1-800-678-4357. You're listening to Radio Rounds with St. Louis Children's Hospital. For more information on resources available at St. Louis Children's Hospital, you can go to stlouishildrens.org. That’s stlouischildrens.org. This is Melanie Cole. Thanks so much for listening.