Gastroenterology, Hepatology and Nutrition

Research Highlights

Our Vision

Our Mission

• Care: We will deliver exceptional, safe, and affordable care 
• Research: We will catalyze high-impact research in digestive diseases 
• Education: We will train the future leaders of the field

Our Values

• We are respectful 
• We are honest 
• We speak the truth 
• We value diversity 
• We work as a team

Innovation in Clinical Care

The location of the division is on the eighth and ninth floors of the Clinical Sciences Building, where clinical, research, and training projects that permits integration to provide the most innovative, evidence- and expert-based care for children with all forms of digestive disease. Delivery of direct patient care is in the Outpatient Gastroenterology Clinic and in inpatient units for Gastroenterology (A4S) and for Hepatology and Liver Transplantation (A4N).

Our team also provides timely consultation to all clinical services at Cincinnati Children’s, where we work as a multi-disciplinary team to improve the care of the children we serve. The scope of care starts with the most common digestive problems and extends to the most rare and complex disorders that require ever-improving technologies to aid in diagnosis and design of new therapies. Some of our specialized services include liver and intestinal transplantation, intestinal rehabilitation, total pancreatectomy and islet cell autotransplantation, inflammatory and complex esophageal and intestinal disorders, and others (described below).

Our medical and nurse specialists also provide care in satellite clinics with the goals to bring gastroenterology expertise to our communities and improve patient experience. We hold daily clinics at the Liberty campus that focus on gastroenterology, an increasing number of subspecialty clinics (example: NASH clinic and Neurogastroenterology/Motility clinic), and gastrointestinal endoscopies. Other satellite gastroenterology clinics take place in Mason, Green Township, Anderson, Northern Kentucky, and Portsmouth. Our experts also hold TeleHealth Gastroenterology Clinics with programs in Kalamazoo (MI) focused on children with liver and intestinal failure, and in Erlanger (TN) focused on children with intestinal failure.

Interdisciplinary Feeding Team

Members:
Scott Pentiuk, MD, Medical Director
Vince Mukkada, MD
Stephanie Oliveira, MD, CNSC

The Interdisciplinary Feeding Team (IFT) provides comprehensive evaluation for children with swallowing/feeding disorders. This multidisciplinary team includes experts from Divisions of Gastroenterology, Hepatology and Nutrition, Otolaryngology, Speech Language Pathology, Occupational Therapy, and Social Services. The IFT evaluated over 1,300 patient visits and 350+ new patients in Fiscal Year 2019. In addition to comprehensive consultation and care, the IFT offers unique multidisciplinary outpatient treatment sessions and child-adult relationship enhancement training for families. Ongoing research projects by IFT investigators include the development and use of the pureed by G-tube diet and methods to evaluate children with swallowing dysfunction. Another important project focuses on the use of quality improvement methods to increase access to patients with swallowing disorders.

Innovation in Education

A T32 grant has provided funding for our training program for over 15 years. Most of our graduates are on academic positions and hold several positions as division chiefs in the US. We believe in our commitment to integrating the clinical and research programs into an arena of opportunities for advanced training in the field of gastroenterology and related subspecialties. Our training programs include:

• Fellowship Program in Division of Gastroenterology, Hepatology and Nutrition
• Advanced fellowship training in the Divisions of Gastroenterology, Hepatology and Nutrition, the Liver Transplant Center, and the Neurogastroenterology and Motility Disorders Center
• Short-term clinical observation/clerkships for US and international trainees
• Research training for international scientists

Below, we present summaries and accomplishments by individual Centers of Excellence.

Digestive Health Center: A catalyst for research on digestive disease

Members:
Jorge Bezerra, MD, Director
Lee (Ted) Denson, MD, Associate Director
Heidi Kalkarf, PhD, Associate Director
Cynthia Wetzel, PhD, Center Manager

The Digestive Health Center (DHC) is one of only 18 Silvio O. Conte Digestive Diseases Research Core Centers funded by the National Institutes of Health in the US, and the only one dedicated to pediatric digestive diseases. Aaron Zorn, PhD, from the Division of Developmental Biology, serves as an associate director. The Center seeks to improve child health through better diagnosis, treatments and outcomes that will emerge from highly innovative work in our four key focus areas: 1) Liver disease modeling, 2) Digestive disease and immunity, 3) Digestive disease and obesity, and 4) Translational embryology. The link for these research focus areas are three scientific cores that provide investigators timely access to state-of-the-art technologies: Integrative Morphology, Gene Analysis, and Pluripotent Stem Cell and Organoid Cores. An additional clinical component facilitates patient-based research. With 83 investigators, the DHC contributes to the research goals of faculty from 19 divisions within the UC Department of Pediatrics and nine other departments within the University of Cincinnati, College of Medicine, with a total extramural grant portfolio of $32.4 million in digestive disease research and 222 digestive disease related articles during the past 12 months. To strengthen pediatric digestive disease, the DHC funds highly promising Pilot and Feasibility projects from junior investigators and sponsors a dynamic enrichment program of scientific seminars, workshops, and annual symposium. The DHC Pilot and Feasibility Program has invested $2.1 million among 49 early stage investigators since 2007. These investigators have since attracted $63.49 million in extramural grant funding.

In addition to the accomplishments described above, the following center investigators received national and international recognition for their clinical, research, and educational accomplishments this past year:

• Jorge Bezerra, MD, president-elect of the American Association for Studies of Liver Diseases and member of the Board of Scientific Councils for NIDDK Intramural Research
• Stacey Huppert, PhD, is organizing and hosting the scientific meeting for the International Symposium on Alagille syndrome
• Heidi Kalkwarf, PhD, RD, Standing Member of the National Institutes of Health Neurological, Aging and Musculoskeletal Epidemiology Study Section for Scientific Review
• Michael Rosen, MD, MSCI, was elected as the chair of the Crohn’s & Colitis Foundation PROKIIDS (Pediatric Resource Organization for Kids with Inflammatory Intestinal Diseases) Research Network
• Takanori Takebe, MD, received the prestigious Japan Academy Medal and was a recipient of the Japan Society for the Promotion of Science Prize

Advanced Nutrition

Members:
Marialena Mouzaki, MD, MSc, Director
Conrad Cole, MD, MPH, MSc
Lee (Ted) A Denson, MD
James E. Heubi, MD
Heidi Kalkwarf, RD, PhD
Samuel Kocoshis, MD
Stavra Xanthakos, MD, MS

Our mission is to optimize nutritional status of children exposed to chronic medical conditions and environmental hardships through surveillance of patients at risk, and identification and implementation of best treatment practices. We seek to improve the prevention and treatment of childhood diarrhea, obesity and undernutrition by implementing best practices and creating new knowledge through bench-to-bedside research collaborations between Cincinnati Children’s and global partners.

Dr. Denson continues collaboration with investigators at the University of Virginia and the Aga Khan University in Pakistan on patient-based studies to define the pathogenesis of environmental enteropathy in affected children. He also leads the first multi-center RCT of the prebiotic 2’-fucosyllactose nutritional supplement in children and young adults with Crohn’s disease and ulcerative colitis.

Dr. Cole continues with collaboration/consulting roles in projects in Ghana focused on micronutrient deficiencies (zinc and iron) in undernutrition and diarrheal diseases. In the past academic year, he developed an active research and clinical collaboration in Sierra Leone.

Drs. Cole and Kocoshis are Center investigators in clinical trials and patient-based research involving patients with intestinal failure.

Drs. Kalkwarf and Heubi are investigating trajectories of bone mineral accrual in young children and the influences of dietary intake, growth, and body composition. These data will establish normal ranges for bone density based on age and enable detection of bone deficits in children with chronic medical conditions.

Drs. Kalkwarf and Xanthakos are investigating deficits in bone density among adolescents with non-alcoholic fatty liver disease (NAFLD), and are also researching deficiencies of iron, vitamin B12 and calcium in adolescents who have undergone bariatric surgery.

Dr. Xanthakos is comparing the impact of lifestyle interventions against weight loss surgery on liver related outcomes and metabolic comorbidities of patients with NAFLD, including the role of dietary changes. Dr. Mouzaki is investigating the intestinal microbiota and the bile acid homeostasis of patients with NAFLD.

Drs. Mouzaki and Xanthakos are investigating the impact of socioeconomic deprivation on the disease severity of patients with NAFLD, including food insecurity. In addition, in collaboration with Dr. Kalkwarf, they are studying the role of nutritional comorbidities, such as bone mineral density, vitamin D deficiency and sarcopenia on NAFLD.

Cincinnati Center for Eosinophilic Disorders

Members:
Phil Putnam, MD, GI Director
Vince Mukkada, MD, GI Associate Director
Scott Bolton, MD

The Cincinnati Center for Eosinophilic Disorders (CCED) is an established multidisciplinary referral center for evaluation and treatment of eosinophilic gastrointestinal disorders in children and adults. Physicians representing the Divisions of Gastroenterology, Hepatology and Nutrition, Allergy and Immunology, and Pathology and Laboratory Medicine provide comprehensive clinical services supported by experienced nurses, dietitians, a psychologist, and a social worker. Over 70% of our patients agree to participate in clinical and basic science research studies. Our clinical research includes important studies of both dietary and pharmacologic management of eosinophilic disorders, and we are continuing to focus on identifying less invasive means of diagnosis and disease monitoring. Drs. Putnam, Bolton, and Mukkada collaborated with other leading investigators in the CCED in studies of genetic and immunologic factors responsible for eosinophilic inflammation in the gut, and in evaluating the effectiveness of biological agents including anti-IL-4 receptor binding antibodies, anti-IL5 receptor binding antibodies, and anti-Siglec8 antibodies, and topical glucocorticoids in the management of eosinophilic disease. The CCED team was the first to investigate eosinophil progenitor (EoP) levels in patients with Eosinophilic Esophagitis (EoE), leading to the identification of a potential new noninvasive biomarker, which is an essential step toward simpler disease monitoring over time, with the potential of reduced discomfort, costs and side effects.

Recent research includes a recently published study using single-cell RNA sequencing identifying eight peparate T cell subtypes residing in the esophageal tissue in active EoE, as well as a likely role for the short chain fatty acid receptor FFAR3 in amplifying local Th2 responses in EoE. In a collaborative effort across a national consortium, we recently published our experience correlating parent and child reported clinical outcomes compared to histology to demonstrate that parent reported outcomes are accurate in describing young patients’ symptoms and quality of life, and correlate well to histology findings. In addition, the CCED, with Marc Rothenberg, MD, PhD, as principal investigator, recently finished work as the central site for a Patient Centered Outcomes Research Institute contract for a multicenter trial examining the efficacy of minimally restrictive empiric diets in the management of pediatric eosinophilic esophagitis. The data from this study shows the effectiveness of only removing one food (milk) for the treatment of EoE. We are currently preparing manuscripts on this topic for publication. We recently published work extending our previous genome wide association study data utilizing the ImmunoChip assay to identify shared disease risk loci between EoE and autoimmune disease, and thus identified a new EoE disease risk loci at 16p13 which highlights a unique shared genetic risk with autoimmune conditions.

We continue to participate in a number of clinical trials of novel therapeutics in eosinophilic GI disease, including phase III trials of a budesonide oral solution and an anti IL4a receptor blocking antibody in EoE, a phase II trial of an anti-Siglec8 antibody in eosinophilic gastritis, and a phase I single center trial of an anti-IL5 receptor binding antibody in eosinophilic gastritis. We continue to expand our knowledge of eosinophilic GI disease beyond the esophagus, with a recent series describing our local experience with eosinophilic colitis and other potential causes of colonic eosinophilia. We continue to involve our trainees in cutting edge research in eosinophilic disease. Completion of projects from recent graduates examine the potential role of estrogen receptors in the pathogenesis of EoE, expanding on our prior work to examine the use of eosinophil progenitor cells as a non-invasive biomarker of EoE disease activity, and identifying the effect of EoE and its treatment on bone health in our local patient population. Ongoing work by current fellows includes a novel characterization of very early onset EoE compared to a control group of patients who present as adolescents, as well as examinations of the development and characteristics of EGID developing in patients who have undergone liver or small bowel transplants.

With support of a five-year, $6.25-million grant from the National Institutes of Health to Dr. Rothenberg, the CCED leads a consortium of organizations with a common goal to conduct clinical research into eosinophilic disorders and to train investigators in how to conduct clinical research. This Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) is a collaboration of clinician investigators, translational scientists, physicians, patients, families, and patient advocacy groups. In addition, it is part of the Rare Disease Clinical Research Network (RDCRN). Work from this collaborative group focuses on studies of the natural history of eosinophilic disease, particularly the comparatively rare types including eosinophilic gastritis and eosinophilic colitis, as well as determining the disease response to less-restrictive diet therapy in adult patients with EoE. This consortium supports a series of pilot studies, including projects examining the use of the angiotensin receptor blocker losartan in the treatment of EoE, assessing the role of elemental diet therapy for eosinophilic gastritis, and examining a less invasive esophageal monitoring system-transnasal endoscopy compared with classic endoscopy. We applied for a competitive renewal of our funding for another five-year cycle of this grant.

Drs. Putnam and Mukkada, along with Drs. Rothenberg and J. Pablo Abonia, MD, from the Division of Allergy and Immunology, and Margaret Collins, MD, from the Division of Pathology and Laboratory Medicine, recently participated in an international consensus committee meeting to update the diagnostic guidelines for eosinophilic esophagitis. Their work led to publication of this new criteria in Gastroenterology last year. Our enhanced understanding of the potential roles of proton pump inhibitors in the diagnosis and treatment of the disease drives this latest revision. The consensus decision making of the larger group was heavily driven by molecular and clinical insights into PPI use in this disease which our group identified and published. Our group will use these new consensus criteria going forward to better standardize our understanding of this disease both in clinical care and research settings.

IBD the Schubert-Martin Inflammatory Bowel Disease Center

Members:
Lee Denson, MD, Director
Michael Rosen, MD, Medical Director
Phillip Minar, MD
Jennifer Hellmann, MD

The Division of Gastroenterology, Hepatology and Nutrition and the IBD Center sees more than 900 patients with IBD each year. Over 100 new patients receive a diagnosis annually, and close to 80 second-opinion patients see physicians from the Schubert-Martin Pediatric IBD Center from more than 20 states and abroad. These numbers reflect a significant increase in total patient volume over the last five years.

The Center is an integral and leading participant in collaborative consortia like the ImproveCareNow Quality Improvement Network and the Crohn’s and Colitis Foundation’s PRO-KIDS Clinical Research Network. Dr. Rosen began a three-year term as PRO-KIDS co-chair this year. This role reflects in superior outcomes for our patients, with 86% of IBD patients within the center being in remission, 65% in sustained remission, and 90% expressing a high level of confidence in disease management. The Center’s website shares transparently these outcome measures. Our Annual IBD Family Education Day, co-hosted by the local chapter of the Crohn’s and Colitis Foundation, continues to be one of the largest educational events of its kind in the country. A rejuvenated and energized Parent Advisory Board partners with Center providers to identify priority areas for improvement, education, increased awareness and community involvement with an active Facebook page.

Physicians within the Center continue to develop and lead basic, translational and clinical research to identify key etiopathogenic mechanisms for inflammatory bowel diseases, minimally invasive biomarkers for predication of disease flares and remission, development of mobile phone apps for patient engagement and self-management, and transition of patients to adult providers. We reported in Lancet results of the first NIH-supported prospective inception cohort study of children with ulcerative colitis, the PROTECT study. In the setting of standardized therapy, we defined clinical, genomic, and microbial factors associated with patient outcomes including steroid-free remission on mesalamine alone and need for escalation to anti-TNF therapy. This data will guide current clinical practice and support our ongoing NIH-supported clinical trial of the 2’-fucosyllactose prebiotic. A study, published in the Journal of Immunology, defined a novel innate lymphoid cell dependent mechanism of intestinal goblet cell expansion which would ameliorate colitis, while a study published in the Journal of Pediatric Gastroenterology and Nutrition defined target infliximab concentrations during induction therapy in children with Crohn’s Disease. These results will help providers optimize a current therapy, infliximab, while also prioritizing a novel approach to directly promote mucosal repair. Collaborators within the institution include members from the James M. Anderson Center for Health System Excellence, the Division of Behavioral Medicine and Clinical Psychology, the Center for Adherence and Self-Management, Pediatric Surgery, the Divisions of Allergy and Immunology, Adolescent and Transition Medicine, and the Department of Radiology continue to make significant contributions to finding a cure as well as improving outcomes and self-management skills for children suffering from IBD.

Interdisciplinary Feeding Team

Members:
Scott Pentiuk, MD, Medical Director
Vince Mukkada, MD
Stephanie Oliveira, MD, CNSC

The Interdisciplinary Feeding Team (IFT) provides comprehensive evaluation for children with swallowing/feeding disorders. This multidisciplinary team includes experts from Divisions of Gastroenterology, Hepatology and Nutrition, Otolaryngology, Speech Language Pathology, Occupational Therapy, and Social Services. The IFT evaluated over 1,300 patient visits and 350+ new patients in Fiscal Year 2019. In addition to comprehensive consultation and care, the IFT offers unique multidisciplinary outpatient treatment sessions and child-adult relationship enhancement training for families. Ongoing research projects by IFT investigators include the development and use of the pureed by G-tube diet and methods to evaluate children with swallowing dysfunction. Another important project focuses on the use of quality improvement methods to increase access to patients with swallowing disorders.

Intestinal Rehabilitation and Intestinal Transplantation

Members:
Conrad Cole, MD, Medical Director, Intestinal Rehabilitation Center
Samuel Kocoshis, MD, Medical Director, Intestinal Transplantation Program
Stephanie Oliveira, MD

These two programs continue to expand their clinical profiles and facilitate the translational and clinical research conducted by both programs. Our circumspect, thoughtful approach to intestinal rehabilitation obviates the need for intestinal transplantation for many of the patients referred for transplantation as less than one in five patients referred for intestinal transplantation get transplanted. Our mission is to provide the best possible care for children with intestinal failure through innovation. Outcomes for both intestinal rehabilitation and intestinal transplantation are excellent. Our central line associated blood stream infection rate of 1.5/1000 catheter days is among the best in North America. We were the lead center for the expanded multicenter pediatric clinical trial funded by Shire/Takeda Pharmaceuticals for the recently approved Teduglutide (Gattex®) with Dr. Kocoshis as the lead investigator and Dr. Cole as co- investigator. Additional studies include the evaluation of the impact of quality of life of the family on the outcome of children with intestinal failure. Dr. Cole, in collaboration with Nana-Hawa Yayah Jones, MD, identified a high prevalence of iodine deficiency in patients on total parenteral nutrition and developed ongoing evaluation and novel therapeutic options for these patients. We continue to monitor these modalities and are actively working on identifying the shortest duration of exclusive parental nutrition that associates with the development of iodine deficiency. In collaboration with our colleagues in the Division of Infectious Diseases, David Haslam, MD and Dr. Andersen; and Dr. Helmrath from Surgery, we are evaluating the interaction of diet and antimicrobials on intestinal microbiome and how this impacts adaptation.

Our small bowel transplant surgical team, led by Jaimie Nathan, MD, is studying microbiome changes in stool and allograft intestinal tissue following intestinal transplantation, to correlate them with diminution of the T-reg population in tissue and blood during intestinal allograft rejection. Additionally, our intestinal transplantation team, noting much better survival with combined liver/intestinal transplantation than with isolated intestinal transplantation, has, as a quality improvement measure, stratified risk for exfoliative rejection by presence or absence of allograft liver in the graft or by presence or absence of preformed or de novo donor specific antibodies (DSA). Patients with a positive DSA receive two-three times higher induction doses. The impact of these strategies is being analyzed with regard to overall survival, length of ICU stay, and length of overall hospital stay.

Liver Diseases

Members:
Jorge A. Bezerra, MD, Director
William F. Balistreri, MD
Akihiro Asai, MD, PhD
Kathleen Campbell, MD
Chandrasherkar Gandhi, PhD
James Heubi, MD
Stacey Huppert, PhD
Alexander Miethke, MD, Associate Director
Anna Peters, MD, PhD
Pranav Shivakumar, PhD
Takanori Takebe, PhD
Amy Taylor, MD
Chunyue Yin, PhD

The Pediatric Liver Care Center provides comprehensive care for children with liver diseases and serves a national and international referral population via a comprehensive evaluation of all medical and surgical aspects of liver diseases. The evaluation includes a full spectrum of metabolic analysis, autoimmune and inflammatory processes, and gene sequencing techniques to diagnose mutations that cause clinical phenotypes. The multidisciplinary nature of the comprehensive care makes the Center a “one-stop-shop” in which the timely consultation with hepatologists, surgeons, pathologists, radiologists, and nutritionists with expertise in pediatric liver disease optimizes patient care. It also catalyzes patient-based research to narrow the knowledge gap and solve clinical challenges with the ultimate goal to improve outcomes.

Physicians, surgeons, and scientists in the Center are performing exciting research with the goals of understanding the mechanisms of liver development, advancing tissue engineering, discovering the causes and pathogenesis of pediatric liver disease, and designing new therapies to block progression of liver injury. Independent grants funds their work from the National Institutes of Health, foundations, and industry and aims at closing the knowledge gap in the field with a focus on translating new discoveries into improved clinical care. One example is Dr. Bezerra’s partnership with Cincinnati Children's clinical laboratories to launch a new clinical assay to quantify MMP-7 in the serum as a biomarker of biliary atresia.

Our faculty published over 20 original scientific reports last year, as shown below as a brief summary of key findings:

• Ledipasvir-Sofosbuvir treatment is an effective treatment for Hepatitis C in children 6-11 years of age (Balistreri, published in Hepatology)
• PKD1L1 is a new susceptibility gene for biliary atresia (Bezerra, published in Hepatology)
• Children with primary sclerosing cholangitis have clinical predictors of outcome (Miethke, published in the Journal of Pediatrics)
• Molecular components of the inflammasome regulate bile duct injury in experimental biliary atresia (Shivakumar, published in Journal of Hepatology)
• Cytokines and hepatic stellate cells regulate inflammatory liver injury (Gandhi, published in the Journal of Biological Chemistry), and ALR has a protective role in liver steatosis (Gandhi, published in the FASEB Journal)
• Hypoxia regulates human liver bud development from pluripotent stem cells (Takebe, published in Stem Cell Reports)
• The use of pluripotent stem cell-derived liver organoids to model hepatitis B virus-host interactions, fatty liver disease and fibrosis (Takebe, published in eBiomedicine and Cell Metabolism)
• IL-2 and Treg cells regulate biliary fibrosis in sclerosing cholangitis (Taylor and Miethke, published in Hepatology)
• Chronic cholestasis impacts bone density and growth (Heubi, published in Hepatology)

We have several lines of ongoing and new clinical and translational investigation addressing mechanisms of disease and new treatments. Examples includes Dr. Balistreri’s studies on the use of direct acting antivirals to treat hepatitis C virus infection in young children, and Dr. Bezerra’s clinical trial assessing the efficacy of Tenofovir in children with chronic hepatitis B infection. Dr. Asai is using CRISPR-editing to introduce patient-specific mutation in pluripotent stem cells, generate inducible hepatocytes, and study mechanisms of cholestasis. In the Center for Autoimmune Liver Disease, Dr. Miethke leads a multi-disciplinary team studying radiological, biomarker, and genetic underpinnings of autoimmune liver disease, with a focus on studies of primary sclerosing cholangitis, and Dr. Taylor is investigating family networks to understand the needs of children with autoimmune hepatitis and sclerosing cholangitis to improve clinical outcome and foster participation in clinical trials. Dr. Miethke will be a Co-PI in new prospective observational and interventional studies for children with primary sclerosing cholangitis as part of the NIH-funded Childhood Liver Research Network. Breaking new ground for transplantation science, Dr. Peters is applying single cell sequencing to study the cellular mechanisms underlying late-onset acute cellular rejection for liver-transplanted children.

In the laboratory, Dr. Huppert is studying mechanisms of cellular plasticity in the liver, with exciting work investigating re-programming mechanisms to regenerate the biliary epithelium. Dr. Gandhi is pursuing studies defining the role of augmenter of liver regeneration in pathogenesis of NASH, and the cellular crosstalk among sinusoidal endothelial cells, hepatic stellate cells and inflammatory cells that regulates fibrogenesis. Using zebrafish models, Dr. Yin is uncovering molecular mechanisms of cell injury and biliary secretion that drive pathogenic mechanisms of cholestatic syndromes.

Neurogastroenterology and Motility Disorders Center

Members:
Ajay Kaul, MD, Director
Khalil El-Chammas, MD, MS
Neha Santucci, MBBS, MD

The Neurogastroenterology and Motility Disorders Center continues to experience growth, with 941 outpatient encounters and 542 manometry procedures (35% increase from prior year) and the addition of a third faculty, Dr. Santucci. Over the past year, the Center received about 40 new referrals per month, primarily from patients outside of our primary service area. Patients came from 31 states and 14 from outside of the US. In addition, the neurogastroenterology team, in collaboration with the Colorectal Center, started an interdisciplinary clinic in July 2014 to evaluate and treat children with complex colorectal and motility disorders such as Hirschprung disease, anorectal malformations, and severe idiopathic chronic constipation with a goal to improve patient outcomes through standardization of practice and clinical research. This year alone, 102 patients from across the nation and overseas received evaluation in this combined multi-disciplinary motility clinic. Due to unprecedented growth of the program, the combined multi-disciplinary motility clinic appointed Dr. El-Chammas, as the medical director.

Among new advances, we expanded our motility program to the Liberty campus, are setting up a mind-gut interaction disorders program and are adding new technology, including EndoFLIP, transrectal ultrasound, percutaneous electric nerve field stimulation and Smartpill to our investigative armamentarium. Dr. Santucci has expertise in functional gastrointestinal disorders and will develop a pain-related functional GI disorders program.

To explore new research opportunities, the Center immersed itself in multicenter trials on the use of percutaneous electric nerve field stimulation in functional gastrointestinal disorders, the characterization of high-resolution colon manometry studies, and the use of mirtazapine in functional abdominal pain.

We started an advanced fellowship in motility disorders and trained our first fellow who has graduated and has joined as faculty at the University of Pittsburgh. This year we are training our second advanced fellow. We have our second clinical observer from Thailand who is spending a year with us on an educational scholarship from his country. This year the team presented the fourth Annual Workshop on Pediatric Manometry testing for physicians and nurses from across the nation.

Pancreas Care Center

Members:
Maisam Abu-El-Haija, MD, Medical Director
Tom Lin, MD, Associate Director

Our vision is to be the leader in delivering world class healthcare to children with pancreatic disease, through comprehensive multidisciplinary management that puts patient outcomes at the forefront of our overarching goals. We implement chronic care algorithms that enhance the care coordination and apply state of the art research methodology to lead our innovation in patient care.

The program, led by Drs. Nathan, MD, Surgical Director; and Deborah Elder, MD, Endocrinology Director, in collaboration with pain team and psychology, currently follows more than 400 patients with various pancreatic disorders including pancreatitis, exocrine pancreatic insufficiency, congenital anomalies of the pancreas, and pancreatic tumors. Since its inception in FY13, the program completed a survey of Cincinnati Children’s providers to better understand the variation in management of acute pancreatitis, assembled a multidisciplinary care team to evaluate and treat complex pancreatic disorders, and established a REDCap database for patient registry.

We put forth efforts to standardize inpatient pancreatitis management through an order set that became the template for other major children’s hospitals and incorporates into their electronic records, for easier delivery and implementation in patient care. We exemplified this in the published report (JPGN PMID: 30921257.) In the past year, we established a robust biorepository for pancreatitis and pancreatic surgical patients for future research initiatives.

The Pancreatic Care Center (PCC) performed the first total pancreatectomy with islet autotransplantation (TPIAT) operation in FY15, and by the end of FY19, we are proud to announce our center performed 50 TPIATs and two subtotal pancreatectomies with IAT for treatment of unremitting pain due to chronic pancreatitis. There were 427 gastroenterology pancreas clinic visits in FY19, an increase of 10% from last fiscal year, and 52 PCC/TPIAT evaluations in FY19 an increase of 4% from last fiscal year.

Our scientific highlights for this past year included cutting edge research findings on the imaging modalities that assess pancreatic function and volume in normal controls and diseased pancreatic patients, and these studies will help shape future grants in this arena. Our clinical and translational studies from the acute pancreatitis registry generated important genetic findings that will advance the understanding of the role of precision medicine in pancreatitis by using the high through-put Pancreas Gene Panel, results recently published in Pancreatology, PMID: 31088717. Our unique program for total pancreatectomy with islet autotransplantation generated important clinical studies regarding the outcomes of the operation in pediatric chronic pancreatitis patients (PMID: 30372594), and we have new basic science research discoveries related to growing human pancreatic ductal and islet organoids publishing soon in one of the Nature journals.

Dr. Abu-El-Haija received K23 NIDDK grant funding for predicting severity and improving the outcomes of acute pancreatitis. The grant is now in the second year of funding. Our Center is participating in NIH-funded multi-center studies (first two studies listed below) that will help advance the care of children with pancreatic disorders, amongst other submitted grants that are awaiting review.

PCC team extramural funding during FY19:

1.NIH U01 Abu-El-Haija (Site PI) - CPDPC INSPPIRE International Study Group to Study Pediatric Acute Recurrent and Chronic Pancreatitis: In Search for a Cure. Cincinnati Children's is the highest recruiting center out of 19 national and international centers.

2.NIH R01 Nathan (Site PI) - Advancing Treatment for Pancreatitis: A Prospective Observational Study of TPIAT. Our Center is the highest enrolling center for pediatric TPIAT nationally in this consortium.

We also widely marketed our Pancreas Gene Panel that we developed and launched in collaboration with the Molecular Genetics Laboratory, and it is now a clinically available test that evaluates 10 genes known to cause inheritable pancreatitis using Next-Generation Sequencing technology. Since the launch in November 2016, we performed steadily about 10 tests/month using the Pancreas Gene Panel. In addition, PCC members are actively involved in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), as Dr. Abu-El-Haija is the vice chair of the pancreas committee and a course director for the National Pancreas Foundation (NPF) annual meeting. In addition, Dr. Abu-El-Haija is on the American Gastroenterology Association Pancreas Selection Committee, the educational chair of Collaborative Alliance for Pancreatic Education and Research (CAPER), and on the planning committees of NASPGHAN, World Congress and European Pancreas Club meetings for this year. Dr. Lin is an active member in the NASPGHAN ERCP Special Interest Group. Dr. Nathan is part of the NASPGHAN Pancreas Committee as well. The PCC at Cincinnati Children's is one of only a few pediatric centers that are an NPF-approved Center of Excellence for pancreatic care in the nation and is a destination sought out by patients from around the nation based on its reputation for excellence in patient care and its commitment to innovative research.

Pediatric Liver Transplantation

Members:
Alexander Miethke, MD, Medical Director
Akihiro Asai, MD
William Balistreri, MD
Jorge A. Bezerra, MD
Kathleen Campbell, MD
Anna Peters, MD, PhD
Amy Taylor, MD

The mission of the Pediatric Liver Transplant Program is to advance the care of liver transplant recipients by providing unparalleled clinical care, addressing gaps in knowledge through patient-based and basic laboratory research, improving health care delivery system through continuous quality improvement, and serving as advocates for organ donation and allocation in our community and country. As one of the largest pediatric liver transplant programs in the country, we performed more the 700 liver transplants since the program began in 1986. Our patient and graft survival rates are at or above the national average at three years post-transplant, and we are performing living donor liver transplantation.

In addition to providing care for the most common pediatric liver disorders leading to transplantations we are able to leverage institutional strengths to provide care and the best outcome available to a number of patients with rare diseases and extremely complex needs. This includes children with advanced liver tumors. Since 2007, the Cincinnati Children's liver transplant team has performed more pediatric liver transplants for hepatic tumors than any other program in the United States. In addition to providing outstanding patient care, the Liver Transplant program is a leader in multicenter clinical and translational research studies and national quality improvement efforts. These include: Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH), the Studies in Pediatric Liver Transplantation (SPLIT) quality improvement community and clinical registry, and the Medication Adherence in Liver Transplant (MALT) study group, and multiple local projects and initiatives. For instance, we developed collaborations with the Center for Transplant Immunology (CTIMM) at Cincinnati to molecularly define transplant rejection responses to ultimately personalize immunosuppression therapies. In pre-clinical studies, Dr. Peters is using single-cell sequencing technology to understand the biological processes underpinning late-onset acute cellular rejection.

Steatohepatitis Center

Members:
Stavra Xanthakos, MD, MS, Director
Catalina Arce-Clachar, MD
Kristin Bramlage, MD
Marialena Mouzaki, MD, MSc, Associate Director

Understanding and treating NAFLD and NASH: The Cincinnati Steatohepatitis Center (CCSC) is a multidisciplinary program that provides care to a growing population of children and adolescents with nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease in the United States, and increasingly in most of the developed world. NAFLD affects one in 10 children and one in three adults in the United States: up to 1/3 of these affected persons can develop a more severe form called nonalcoholic steatohepatitis (NASH) that can progress to severe fibrosis. NASH-related cirrhosis has become one of the leading causes of liver transplant in adults, especially among younger adults. Early identification and intervention is critical to prevent progression to end-stage liver disease.

Because there is a close association of NAFLD and NASH with obesity, cardiovascular disease, prediabetes and diabetes, the CCSC collaborates with the Center for Better Health and Nutrition, the Sleep Center, the Hypertension Clinic, the Lipid Clinic, the Diabetes Center, and the Surgical Weight Loss Program for Teens to help identify and manage comorbid conditions and help patients achieve a healthier weight, the current first-line treatment.

Our program completed over 650 patient visits in fiscal year 2019. Given the high prevalence of this disease, our program now offers clinics at our base, Liberty and Anderson locations, with four faculty members, including Drs. Arce-Clachar, Bramlage, Mouzaki, and Xanthakos. Because patients of Hispanic ethnicity carry a high burden of NAFLD and may face additional barriers to accessing healthier lifestyles, we now offer a clinic staffed by Dr. Arce-Clachar, who is bilingual in Spanish and English, to improve communication.

Our program also seeks to develop more broadly effective prevention and intervention strategies for NAFLD. We are a leading pediatric site in the NIDDK-funded NASH Clinical Research Network (NASH-CRN), a multi-center consortium investigating the natural history and determinants of NASH in adults and children and conducting trials of novel therapies, including an ongoing randomized control trial of losartan for the treatment of NAFLD in children. In 2018, we also joined TARGET-NASH, a multi-center observational cohort study that will examine natural history and comparative effectiveness of diverse treatments in populations under-represented in phase II and phase III clinical trials. The CCSC has an ongoing NIH-funded clinical trial comparing the effectiveness of comprehensive lifestyle intervention to bariatric surgery in treating NASH in severely obese adolescents. Additional published research highlights in 2019 included identifying that psychotropic medication usage associates with increased liver disease severity in a cohort of 228 children with biopsy-confirmed NAFLD. We also found that 8% of the 740 children diagnosed with NAFLD (since 2010 in our program) may have a unique phenotype characterized by significant hypobetalipoproteinemia and present with similar severity of NAFLD but at younger age, lower BMI and waist circumference. Alimentary Pharmacology and Therapeutics, Gastroenterology, Obesity, New England Journal of Medicine, Nature, JAMA Pediatrics, Journal of Pediatrics, Journal of Pediatric Gastroenterology and Nutrition, Nature Reviews Gastro Hepatology, and others published work by the CCSC investigators.