October 9, 2020

The Search for Biomarkers to Aid in the Diagnosis and Treatment of Pediatric Acute Liver Failure

Meet Mike Leonis, MD, PhD

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A rapidly progressing condition with high morbidity and mortality rates, pediatric acute liver failure (PALF) is not well understood, particularly when the etiology is indeterminate. This is the area of focus for Mike Leonis, MD, PhD, newly appointed Medical Director of Pediatric Liver Transplantation at Cleveland Clinic Children’s.

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Consult QD recently had the opportunity to interview Dr. Leonis, a recognized expert in the field, about his goals for the pediatric liver transplant program at Cleveland Clinic Children’s.

Pediatric liver transplant physician returns to Ohio

Consult QD: You are now back in Ohio after three years in Alabama as Medical Director of the Pediatric Liver Transplant Program at Children’s Hospital of Alabama, Birmingham. What made you want to return to the state, and what does it mean for you personally to take on this position at Cleveland Clinic?

Dr. Leonis: It feels great to return to the region of the country that has always brought my wife and I so much pleasure. We have lots of friends throughout Ohio and our son just graduated from Case Western Reserve University, so we’ve been in the Cleveland area many times while he was attending college. And, of course, Cleveland Clinic is a phenomenal institution with an incredible dedication to advanced healthcare for pediatric and adult patients alike.

Before my position in Birmingham, I had lived and worked in Ohio since 1999, when I did my fellowship in pediatric gastroenterology, hepatology and nutrition at Cincinnati Children’s, which is a large, highly regarded pediatric liver transplant program and a regional referral center. I was on staff there for 18 years as a pediatric transplant hepatologist, and I’m eager to share my expertise in advancing Cleveland Clinic Children’s pediatric liver transplant program into a regional and national referral center as well.

Consult QD: What drew you to your specialty?

Dr. Leonis: Well, I’ve had a long-standing interest in biochemistry. It was my undergraduate major, and molecular biology was the focus of my PhD. Then, as I moved through clinical training, I did my residency in pediatrics and a fellowship in pediatric gastroenterology, hepatology and nutrition, which was the subspecialty that excited me the most. It was a natural fit for me to gravitate toward hepatology from there, since the liver is the center of the body’s biochemistry.

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The quest to identify biomarkers in pediatric acute liver failure

Consult QD: Can you describe your research efforts?

Dr. Leonis: My primary research interest is pediatric acute liver failure (PALF), a rapidly progressive and potentially fatal disease that has multiple etiologies and a diverse array of clinical treatments and outcomes. We typically only have 3–7 days to figure out what’s going on with a patient and to decide whether the patient needs an immediate liver transplant. I’ve been involved with the PALF research network, a consortium of hepatologists from 20+ institutions in the U.S. and Canada, for the past 15 years. The group was formed because most institutions only see about 3–5 cases of PALF per year, which is not a large enough volume for any one center to seriously study alone. It’s been rewarding to be a part of the PALF research network, because we’ve been successful in learning a lot about the etiologies of PALF and in particular a subset of those with the disease called indeterminate PALF.

Consult QD: What are takeaways from your recent paper in Hepatology on biomarkers linked to CD8+ lymphocytes in PALF?

Dr. Leonis: In a nutshell, we found that patients with indeterminate PALF (compared to those with defined PALF diagnoses) had a significant degree of immune dysregulation that is driving the disease process. In the blood of PALF patients collected within six days after enrolling into the study, we found four circulating T-lymphocyte activation markers can identify PALF patients with a high degree of immune activation, and this high immune activation group was more likely to have an indeterminate etiology associated with a worse clinical outcome. So now, within the first couple of days of the onset of their illness, we can identify those patients with a high degree of immune activation and target them for either immune therapies or as candidates for liver transplant. Hopefully, this type of approach will vastly improve clinical outcomes in the future.

Looking forward

Consult QD: What do you consider the most exciting areas of opportunity in the field in the next 5-10 years?

Dr. Leonis: In addition to improving our understanding of the beast that is pediatric acute liver failure, nationally, one of the most exciting things in pediatric hepatology is growing the methods and infrastructure for recruiting and utilizing anonymous living donors for liver transplantation. In fact, Cleveland Clinic is already a leader in this area, and currently has the 3rd highest volume in the nation for using anonymous living donors in pediatric liver transplantation. In addition, as we make the transplant surgery safer for donors by doing the procedure laparoscopically, we hope to be able to expand the pool of donors available to recipients in need.

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Consult QD: And what are your goals for your tenure at CCF?

Dr. Leonis: Cleveland Clinic Children’s has a well-established pediatric liver transplant program with an incredibly strong cohort of pediatric transplant and transplant surgeons (Koji Hashimoto, MD, PhD, Vera Hupertz, MD, Kadakkal Radhakrishnan, MD, Deborah Goldman, MD, and Karen Murray, MD, who is the Chair of the Pediatrics Institute).

I’m hoping we can heighten awareness of our pediatric hepatology and liver transplant programs among referring physicians so that they recognize not only that this incredible team is in place at Cleveland Clinic Children’s, but that we offer unique pediatric liver transplant services (such as medical expertise in metabolic liver disease and acute liver failure and surgical expertise in performing advanced living donor laparoscopic techniques) associated with excellent clinical outcomes for patients.

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