The Children’s Hospital of Philadelphia is one of 14 clinical sites and a data-coordinating center participating in the Childhood Liver Disease Research Network (ChiLDReN).
ChiLDReN is comprised of a collaborative team of physicians, nurses, research coordinators, and patient support organizations in North America working together to improve the lives of children and families dealing with rare liver diseases.
The ChiLDReN consortium represents the merger of two previous networks, the Biliary Atresia Research Consortium (BARC) and the Cholestatic Liver Disease Consortium (CLiC), and has expanded to include an additional group working to improve the lives of children with cystic fibrosis liver disease (CFLD).
This large collaborative network brings together teams of experts all focused on speeding up the science needed to find new diagnostic tools, understand the genetic reasons for liver diseases, and deliver new treatment options for children with rare liver disease.
The Network is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a division of the National Institutes of Health.
Clinical research protocols supported by the ChiLDReN consortium include the following.
A prospective database of infants with cholestasis
This is an observational study that enrolls children between 0–180 days of age who are cholestasic (serum direct bilirubin of 2 mg/dl or greater and >20 percent of the total bilirubin).
The observational database collects information from office visits, hospital stays and surgeries. This information will be used to develop a better understanding of the natural history of infants with liver disease. Specific information will be gathered that will aid the understanding of factors which might predict clinical outcomes, such as age at diagnosis and age of the surgery.
Participants are followed for up to 10 years. Researchers hope to develop a better understanding of medical complications and rate of progression of liver disease, as well as health-related quality of life, school performance and neurodevelopmental outcome.
Serum, plasma, tissue and DNA are stored for future studies. For example, these samples might be used to develop new diagnostics, or to identify genetic or viral processes involved in pathogenesis.
Biliary atresia study in infants, children and adults
The purpose of this observational database study is to collect the pertinent clinical information, genetic material and body fluid samples to enable investigators to address the following hypotheses:
- To identify the gene or genes implicated in the etiology of biliary atresia
- To identify polymorphisms that may be important in disease progression such as HLA polymorphisms
- Characterize the natural history of the older, non-transplanted child with biliary atresia
Children with biliary atresia, both pre and post-transplant are eligible to enroll up to age 25. Those with their native liver will have clinical information collected yearly for 10 years.
A longitudinal study of genetic causes of intrahepatic cholestasis
This 10-year longitudinal, observational study will investigate the natural history and progression of four genetic causes of intrahepatic cholestasis in childhood:
- Alagille syndrome
- Alpha-1 antitrypsin deficiency
- Bile acid synthesis defects
- Progressive familial intrahepatic cholestasis
This study aims to:
- Determine the clinical phenotype and natural history of each of the four liver diseases during childhood and early adulthood
- Determine the frequency of poor growth and decreased bone mineral density and its predictors in all four diseases
- Develop a repository of serum, urine, tissue and DNA specimens that will be used in future ancillary studies to determine circulating biomarkers that predict disease progression and outcomes
- Identify modifier genes that influence the incidence, severity and progression of liver disease among genetically affected individuals
A longitudinal study of mitochondrial hepatopathies
In this protocol, mitochondrial hepatopathies in children and young adults will be investigated. The focus will be on respiratory chain defects (RC) and defects of fatty acid oxidation (FAO).
There is little known about the full spectrum of severity and long-term natural history of mitochondrial hepatopathies. Moreover, these disorders have not been subject to prospective, rigorous clinicopathological scrutiny.
The specific aims of this study are to:
- Determine the clinical phenotypes and natural history of hepatic RC and FAO disorders
- Determine the correlation between genotype and phenotype
- Determine if circulating biomarkers reflect diagnosis and predict liver disease progression and survival with the native liver
- Determine the clinical outcome of these disorders following liver transplantation
- Develop a repository of serum, plasma, urine, tissue and DNA specimens that will be used in ancillary studies
For more information, visit Childhood Liver Disease Research Network.