Biliary Atresia Clinical Care Program

Biliary Atresia Research: Clinical and Collaborative Studies

The Fred and Suzanne Biesecker Pediatric Liver Center Research Programs at The Children's Hospital of Philadelphia offer children with liver disease a depth of expertise unique among programs worldwide. The Center uses a bench-to-bedside approach that integrates clinical care, clinical research and basic science research. A community of physicians, nurses, surgeons, pathologists, immunologists and geneticists have come together to focus on advancing and improving the care of children with liver disease.

The clinical research initiatives pertaining to liver disease focuses on the following diseases and conditions:

The aims of these projects are often achieved through collaboration with other national and international pediatric Centers. The sponsorship of these projects comes from the Biesecker Foundation, the National Institutes of Health (NIH), and industry.

Ongoing collaborations, consortia studies and investigator-initiated projects include the following.

Childhood Liver Disease Research and Education Network

funded by NIH

The Children’s Hospital of Philadelphia is one of 16 clinical sites and a data-coordinating center, participating in the Childhood Liver Disease Research and Education 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 accelerating the science that is needed in order to discover new diagnostics, understand pathogenesis 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.

The diseases studied as part of ChiLDREN include:

Clinical research protocols supported by the ChiLDREN consortium include:

PROBE (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 surgical portoenterostomy for biliary atresia.

Participants are followed for up to 10 years in order to develop a better understanding of medical complications, 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.

START (a randomized, double-blind, placebo-controlled trial of corticosteroid therapy following Kasai portoenterostomy)

This is a randomized controlled trial designed to study the efficacy and safety of high-dose perioperative corticosteroids following Kasai portoenterostomy.

The primary outcome is serum bilirubin at 6 months after surgery and the secondary outcomes include survival with native liver at 2 years of age.

Toxicity measures being investigated include adverse events, vaccine responses, infections, neurodevelopmental outcomes and GI bleeding.

BASIC (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:

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.

LOGIC (longitudinal study of genetic causes of intrahepatic cholestasis)

This longitudinal (10-year), observational study will investigate the natural history and progression of four genetic causes of intrahepatic cholestasis in childhood:

This study aims:

MitoHep (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:

  1. to determine the clinical phenotypes and natural history of hepatic RC and FAO disorders,
  2. to determine the correlation between genotype and phenotype,
  3. to determine if circulating biomarkers reflect diagnosis and predict liver disease progression and survival with the native liver,
  4. to determine the clinical outcome of these disorders following liver transplantation, and
  5. to develop a repository of serum, plasma, urine, tissue and DNA specimens that will be used in ancillary studies.

For more information, visit http://www.childrennetwork.org.

Additional studies

Pediatric Acute Liver Failure Study Group

The Pediatric Acute Liver Failure (PALF) Study is a multicenter, multinational collaborative study aimed at identifying, characterizing and developing management strategies for infants, children and adolescents who present with acute liver failure.

Because ALF is such a rare disease, a collaborative network was established that collects information and blood samples to help advance our understanding of this rare and serious problem. The Pediatric Acute Liver Failure Study Group consists of 19 pediatric centers, with headquarters at the University of Pittsburgh.

For more information, visit PALF Study.  

Studies in Pediatric Liver Transplantation (SPLIT)

SPLIT, is a research effort that was organized in 1995 by a group of physicians and surgeons committed to the success of pediatric liver transplantation. The group represents a cooperative effort between transplant centers in the U.S. and Canada to prospectively collect and analyze information required to advance the science of pediatric liver transplantation.

All children waiting for transplantation or recovering after transplantation can participate in Studies of Pediatric Liver Transplantation (SPLIT), a multicenter prospective study to collect scientific data on pediatric liver transplantation.

The data collected are stored in a national database and provide information about the practices and outcomes of pediatric liver transplantation in the United States and Canada.

iWith (clinical trial for the immunosuppression withdrawal for stable pediatric liver transplant recipients)

Advances in immunosuppression and surgical care have improved short-term patient and graft survival for liver transplant recipients but left us with different challenges — maintaining the allograft function while minimizing the long-term immune and non-immune complications related to immunosuppressive medications.

This is arguably most important for children who face a long life span and, consequently, a greater potential to develop significant allograft and other end-organ damage.

The iWith clinical trial addresses this challenge by assessing the effectiveness and safety of immunosuppression withdrawal in a well-defined population of pediatric liver transplant recipients whose inherent immune status may predispose to operational tolerance.

PEDS-C Trial (pegylated interferon +/- ribavirin for children with hepatitis C)

The purpose of this clinical trial was to determine the safety and efficacy of peginterferon alfa-2a (PEG-2a) in combination with ribavirin (RV) and PEG-2a alone for the treatment of chronic hepatitis C virus (CHC) infection in children.

This study was completed in 2010 and in August of 2011, the FDA approved the expanded use of peginterferon alfa-2a and ribavirin, allowing for use of the combination treatment in pediatric patients ages 5-17 with chronic hepatitis C (HCV) who have compensated liver disease and no prior history of interferon therapy.

This study is now in the long-term follow-up period to determine the impact of therapy on growth and development.

Entecavir trial for pediatric patients with chronic hepatitis B virus infection who are HBeAg positive

This is a comparative, randomized, double-blinded, placebo-control, multicenter study, assessing the efficacy and safety of Entecavir (Baraclude) in pediatric subjects with chronic HBV infection who are HBeAg-positive and have not received previous treatment with a nucleos(t)ide therapy.

Eligible subjects will be between the age of 2 and < 18 years of age at time of enrollment. After concluding the treatment phase of the study, all subjects will be followed in an observational long-term follow up phase until they complete a total of five years of study participation.

Associated research faculty

For more information

To learn about basic biliary atresia research or clinical research opportunities at the Biesecker Pediatric Liver Center or any of its affiliates, please contact us at 215-590-2525.

  • Print
  • Share

Contact Us