Update Course Rewind: MMP-7 & Biliary Atresia Diagnosis 2024

Global cast MD, along with Cincinnati Children's Hospital, sharing knowledge to improve child health around the globe. Hello PDF research group, Emily. I'm Em Gaudi from Cincinnati Children's Hospital Medical Center. Our 12th annual update course in pediatric surgery was held past August. In this video series, we'll recap the sessions and share the main highlights with you. This year, we introduced a new approach to classify practice changing ideas at our update course. Presentations now fall into three categories. Green Circle for Establish Practice, Blue Square for Promising Newer Practice, and Black Diamond for Early Adopted Practice Only. Here Dr. Greg Tiao, the surgical director of the Liberty Transplantation Programme since Cincinnati Children's. We'll explain the use of MMP 7 as a diagnostic tool in Biliary Attreja. What we're going to try to touch on is a concept which is the timely diagnosis of Biliary Attreja is critical to prolong the native liver survival. Challenge, of course, is we all face is that oftentimes these kids come in late. They take a little bit of time to work up. As a result, we're offering surgery at later and later stages. So the key to treating Biliary Attreja is making an early diagnosis. This is where this biomarker that really came out of Georgia Bazar is my research mentor. He identified MMP 7 about 10 years ago as a diagnostic biomarker for Biliary Attreja. And this all ties to this critical concept that I think we all know, but we don't necessarily integrate, which is you've got to get your cut-size done as soon as possible. The sooner and sooner you get it done, the more likely you'll save the native liver. So this actually was a little guy who showed up just a couple of weeks ago on our service here. I'm 38-day-old child, has a little bit of John this, has McConeum on the first day. He's gaining weight, pediatricians as well as physiologic John, this is a newborn. But then the John this persists, his stool is clay-colored and his lab results are consistent with Biliary Attreja. This is when things start to escalate. We then refer them into a hepatologist who then starts a work-up. And of course, they'll get an ultrasound here and in this particular case, it had pretty classic findings for Biliary. The challenge for pediatrician space is the differential diagnosis for neonatal jaundice, which includes a long list of potential causes. The key is to distinguish B.A. from other non-physiologic, colostatic jaundice conditions so that we can get our cut-size done at earlier early stages. So we have a patient like this and have an ultrasound that's suspicious for Biliary Attreja. What are you going to do? Those of us who are doing Cicis, what is your decision making here? All of those options are actually correct, because it depends on your institution, right? At our institution, we stopped doing a high-dose scan about 25 years ago. The challenge that we face with a high-dose scan is it adds about five days to this study. And data from a recent Mid-Best Study shows that for every 10-day delay in treatment, outcomes are worsened by 20%. But it is one of those things where the earlier we can intervene, the better off it will be. And so this translates to some work that led to this MMP7 study. So about 10 years ago, Georgia took on some data from the Children's Network. Children's Network is a national consortium of about 14 centers in which all the colostatic liver disease children were enrolled in the registry. And Dr. Bizarra took about 70 or so patients from that, some who had Biliary Attreja, some had idiopathic colostasis and some proteomics on that. And he screened about a thousand proteins and they actually found 70 or so that were elevated in the VA population, of which MMP7 was the most clear. The challenge he faced was that, even within the Children's Network, the disease frequency is low, with only 200 to 300 cases per year. This made it very difficult to conduct another study for validation. Well, this is where he took advantage of the incidents being higher in the Far East. Dr. Bizarra was able to validate the findings in just two years through a study conducted in mainland China, where the frequency of Biliary Attreja is much higher. And of course, they really strive to get those kids a good side very early because if they don't, living on a liver transplant is their only option. And it's not readily available. And so those kids face the mortality risk. So MMP7 is not evaluated by a marker for Biliary Attreja. It's not perfect. Actually, if you just look on the table here, the sensitivity is pretty good, but the cutoffs that the different teens use vary. Because it's an acid that's still evolving in front of our eyes, and depending on how you do it. This only stood the next important question. When will you perform the Cassai procedure? Our commitment to our patients who come to our institution is within seven days of them showing up. They have it, they're in the hour. Here is a study from the Children's Network in which they showed that the average day of a Biliary Attreja patient going through Cassai in North America was around 75 days. This one came from Europe where they actually showed that if you did your Cassai before 45 days, you'd actually reduce the incidence of transplant need in that patient population. All of this is driving the integration of MMP7 into the diagnostic process, allowing for earlier diagnosis and getting patients to a Cassai procedure as soon as possible. And this is really the last point, which is a Cassai Pornorosmidun before 45 days is a goal. We actually will do it before 30 days if we can establish the diagnosis because nowadays more and more nurseries are screening their kids at discharge. If you have a direct delivery of an over one in the newborn period, that's also very sensitive for Biliary Attreja. So those kids get plugged into GIT soon and soon. In conclusion, tiny diagnosis of Biliary Attreja is vital for native liver survival, as early intervention through the Cassai procedure greatly improves outcomes. MMP7 has been validated as a biomarker to aid in earlier diagnosis, though it's as they continuously evolve. Research highlights the importance of performing the Cassai procedure within 45 days, with some institutions striving for a 30-day target to reduce the need for transplants and enhance survival rates. Thank you for watching this video. GlobalCast MD, along with Cincinnati Children's Hospital, sharing knowledge to improve child health around the globe.