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

Global Cat MD along with Cincinnati Children's Hospital sharing knowledge to improve child health around the globe. Hello pediatric surgery family. I'm Em Goddy 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 established practice, blue square for promising newer practice, and. Black Diamond for early adopter practice only. Here, Doctor Greg Tea, the surgical director of the liver transplantation program at Cincinnati Children's, will explain the use of MMP 7 as a diagnostic tool in biliary atresia. What we're gonna try to touch on is a concept which is a timely diagnosis of biliatresia is critical to prolong the native liver survival. Challenge, of course, as 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 are offering surgery at later and later stages. So the key to treating biliaryresia is making an early diagnosis. And this is where this biomarker that really came out of Georgia Bezarra's lab, my, my research mentor, he identified MMP 7 about 10 years ago as a diagnostic biomarker for biliary atresia. And this all ties to this critical concept that I think we all know, but we don't necessarily integrate, which is you gotta get your casa 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, a 38 day old child, has a little bit of jaundice, passed meconium on the first day. He's gaining weight, pediatrician says, oh, it's physiologic jaundice of a newborn. But then the jaundice persists, his stool is clay colored, and his lab results are consistent with biliarytresia. This is when things start to escalate. We then refer them into a hepatologist who then starts a workup. And of course, they'll get an ultrasound here, and in this particular case, it had pretty classic findings for biliotresia. The challenge pediatricians face is the differential diagnosis for neonatal jaundice, which includes a long list of potential causes. The key is to distinguish BA from other non physiologic cholestatic jaundice conditions so that we can get our cass done at an earlier and earlier stage. So we have a patient like this and have an ultrasound that's suspicious for biliary atresia. What are you going to do? Those of us who are doing CSIS, 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 HIDA scans about 25 years ago. The challenge that we face with the, uh, a HIDA scan is it adds about 5 days. To this study and data from a recent Midwest study shows that for every 10 day delay in treatment, outcomes worsen by 20%, but it is one of those things where the earlier we can intervene, the better off we'll 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 cholestatic liver disease children were enrolled in the registry, and Doctor Bizarra took about 70 or so patients from that, some who had biliary resia, some had idiopathic cholester. Thesis and did some protein mix on that. And he screened about 1000 proteins and they actually found 70 or so that were elevated in the VA population, of which MMP 7 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 incidences being higher in the Far East. Doctor Baizara was able to validate the findings in just 2 years through a study conducted in mainland China, where the frequency of biliaryresia is much higher. And of course, they really strive to get those kids a cassiah very early because if they don't, living donor liver transplant is their only option and it's not readily available. And so those kids face a mortality risk. So MMP 7 is not. A validated biomarker for biliary atresia. It's not perfect. And actually, if you just look on the table here, the sensitivity is pretty good, but the cutoffs that the different teams used vary because it's an assay that's still evolving in front of our eyes and depending on how you do it. This all leads to the next important question when will you perform the CASAi procedure? Our commitment to the patients who come to our institution is within 7 days of them showing up. If they have it, they're in the OR. Here is a study from the Children's Network in which they showed that the average death of a biliary tresia patient going through Kasai in North America was around 75 days. This one came from Europe, where they actually showed that if you did your Kasai before 45 days, you'd actually reduce the incidence of transplant need in that patient population. All of this is driving the integration of MMPC. 7 into the diagnostic process, allowing for earlier diagnosis and getting patients to a CASA procedure as soon as possible. And this is really the last point, which is a Kasai port neurostomy done before 45 days is the goal. We actually will do it before 30 days if we can establish a diagnosis because nowadays, more and more nurseries are screening their their kids at discharge. And if you have a direct bilirubin over. One in the newborn period, that's also very sensitive for biliaryresia, so those kids get plugged into GI teams sooner and sooner. In conclusion, timely diagnosis of biliarytresia is vital for native liver survival, as early intervention through the Kasai procedure greatly improves outcomes. MMP 7 has been validated as a biomarker to aid in earlier diagnosis, though it's IA continues to evolve. Research highlights the importance of performing the CASAI 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. Global Cat MD along with Cincinnati Children's Hospital, sharing knowledge to improve child health around the globe.