Gastroenterology, Hepatology and Nutrition

Staffed by nine pediatric hepatologists, the Chronic Liver Disease Program serves a national and international referral population via a comprehensive evaluation of all medical and surgical aspects of liver disease and offers prompt initiation of conventional and innovative treatments. The evaluation includes a full spectrum of metabolic analysis, inflammatory processes and high-throughput gene sequencing to screen for genetic diseases. The clinic allows for timely consultation with surgeons, pathologists, radiologists and nutritionists with expertise in pediatric liver disease, thus enabling a thorough evaluation of the impact of the illness on the child’s well-being. For children with advanced stages of liver disease, an evaluation for liver transplantation and close follow-up in the pre-transplant clinic enable the implementation of the most comprehensive treatment protocol to minimize complications and improve post-transplant course.

Recognizing that research is critical to improved care, clinic staff members lead multicenter studies sponsored by the National Institutes of Health to advance knowledge on mechanisms of pediatric liver disease and to develop diagnostic and treatment modalities. Recent innovations include: 1) the development of a high-throughput gene chip to diagnose mutations in children with genetic liver diseases, 2) an ongoing trial to determine the efficacy of corticosteroids in children with biliary atresia, 3) a study to examine the role of immune dysregulation in the etiology of acute liver failure, 4) studies to discover biomarkers and therapies for fatty liver disease, and 5) the development of therapies for bile acid disorders. The clinical and research programs create an outstanding environment for the training of future leaders in the field via a fellowship training program in advanced hepatology. 

The Intestinal Rehabilitation Program has experienced considerable growth during the past year to position itself for a national leadership role in conducting basic scientific, translational and clinical research. The multidisciplinary initiative to standardize care and facilitate research among the three disciplines (gastroenterology, neonatology and surgery) providing care to infants and children with intestinal failure was implemented. Currently the rate of survival without significant liver disease (as measured by cholestasis) of our patients with intestinal failure is among the highest nationally. Major clinical initiatives include weekly multidisciplinary bedside rounds; development of a specific emergency department protocol for standardized evaluation and treatment of fevers among children with central venous catheters; and pre-clinic planning meetings, which are expected to improve the patient’s clinic experience. In addition, we have protocolized management of central venous catheters with suspected bacterial biofilms by initiating ethanol lock therapy and laboratory assessment of nutritional markers. These initiatives have significantly reduced the incidence of outpatient acquired central line bloodstream infections.

Translational and clinical trials research initiatives were also implemented. These include evaluating the relative value of biomarkers of infection (sTREMs [triggering receptors of myeloid cells] and LBP [lipoprotein binding protein]) for identifying acute bloodstream infections (BSI) and for predicting need for liver/bowel transplant and death among our population on total parenteral nutrition (TPN). Other studies include developing in vitro culture methods to grow and expand both normal and diseased intestinal tissue from patients with intestinal failure; validating the use of bomb calorimetry as a measure of enteral energy balance among intestinal failure patients; and feeding advancement trial in patients with gastroschisis to identify the method that optimally decreases the duration of TPN. We continue participation in the 15-center Pediatric Intestinal Failure Consortium and are in the process of analyzing data describing factors impacting outcomes in pediatric intestinal failure.

The number of patients receiving multidisciplinary care for IBD has continued to grow, with children from more than 25 states seen over the past year. State-of-the art services including diagnostic imaging modalities, which do not require radiation exposure, and targeted psychology interventions for nonadherence have been implemented. We have continued to contribute to international genome-wide association studies to identify susceptibility genes specifically for pediatric-onset disease. Investigators have received funding from the National Institutes of Health (NIH) to develop the first multicenter North American randomized controlled trial in newly diagnosed children with ulcerative colitis, the PROTECT study.  Within this trial, we will develop a model to predict individual patient therapeutic responses and clinic outcomes that will incorporate clinical, genetic and immune biomarkers that we have developed.  At Cincinnati Children’s, this trial will include collaborators in the Divisions of Pulmonary Biology and Biomedical Informatics.  Under the leadership of Kevin Hommel, PhD, in the Adherence Center, we will be one of three centers to participate in the first randomized controlled trial of telehealth interventions to improve medication adherence in children with IBD.  

It is anticipated that the knowledge gained from these studies will be rapidly translated to practice through our collaborations with Peter Margolis, MD, PhD, in clinical effectiveness, via his leadership of the ImproveCareNow (ICN) pediatric IBD quality improvement network.  The IBD Center has continued to play a leading role in ICN, which has achieved a 20 percent improvement in patient remission rates with implementation of consensus patient care guidelines and practices. This network was the basis for an NIH award to Margolis in the Center for Health Care Quality to develop an innovative web-based social networking model to improve outcomes for children with IBD, termed C3N. As part of this collaborative network, patient-focused activities are being developed to improve patient outcomes and engage patients and their families to become more involved in the care of their IBD. A pilot trial of daily symptom assessment using innovative bioinformatics tools was undertaken with the patient participating in daily and weekly surveys of the symptoms and QOL measures.