A Prospective Database of Infants With Cholestasis

This is a multi-center project to establish a prospective database of clinical information
and a repository of blood, and tissue samples from children with diagnoses of neonatal liver
diseases, such as biliary atresia (BA), idiopathic neonatal hepatitis (INH), and specific
neonatal presentations of genetic cholestatic disorders in order to perform research in these
important liver problems. Children will be screened and enrolled at presentation at the
participating pediatric liver sites. Participants diagnosed with BA will be followed
intensively for the first year, at 18 months of age, and then annually up to 20 years of age,
or liver transplantation. Other participants diagnosed with cholestasis will be followed on
the same schedule; if there is complete (clinical and biochemical) resolution of their
underlying liver disease off all therapy, there will be one follow up visit within one year
(preferably scheduled at the time of the next planned follow up visit or at 12 months of age,
whichever is later) for data collection and to obtain blood samples. The development of a
serum and tissue bank of specimens from children with various neonatal cholestatic disorders
will be an invaluable tool for current and future investigations into the etiology and
pathogenesis of hepatobiliary injury in the infant.

Detailed clinical data, laboratory investigations, liver and biliary specimens, and long-term
follow-up of outcomes are part of the normal standard of care with respect to the diagnosis
and treatment of the subjects with liver problems. This research involves the collection of
diagnostic, clinical and outcome data concerning the subject, which is kept without
identification (coded) in a national research database of infants with liver disease. Samples
of blood will be obtained for later research analysis, whenever possible, at the time of
clinically indicated blood draws or when there is IV access for a clinical procedure. When
liver biopsy specimens are obtained for diagnostic purposes, any liver biopsy specimen in
excess of that needed for diagnostic use will be sent to the tissue repository. When a
portoenterostomy or liver transplant occurs, sections of the liver and, biliary remnant
removed in the course of surgery and in excess of that needed for diagnostic use, will be
sent for the repository. These specimens will be used in investigations into the mechanisms
and causes of the liver damage that occur in the participant's condition. . All data from
this study will be kept in a secure research database at the DCC and transferred to the NIDDK
data repository after the study ends.

INCLUSION CRITERIA

- Infant's age less than or equal to 180 days at initial presentation at the ChiLDREN
clinical site.

- Diagnosis of cholestasis defined by serum direct or conjugated bilirubin greater than
20% of total and greater than or equal to 2 mg/dl.

- The subject's parent(s)/guardian(s) willing to provide informed written consent.

EXCLUSION CRITERIA

- Acute liver failure.

- Previous hepatobiliary surgery with dissection or excision of biliary tissue.

- Diagnoses of bacterial or fungal sepsis (except where associated with metabolic liver
disease)

- Diagnoses of hypoxia, shock or ischemic hepatopathy within the past two weeks (If the
cholestasis persists beyond two weeks of the initiating event, the infant can be
enrolled).

- Diagnosis of any malignancy.

- Presence of any primary hemolytic disease (except when diagnosed with biliary atresia
or another cholestatic disease being studied by ChiLDREN).

- Diagnosis of any drug or TPN-associated cholestasis (except when diagnosed with
biliary atresia or another cholestatic disease being studied by ChiLDREN).

- Diagnosis with ECMO-associated cholestasis.

- Birth weight less than 1500g (except when diagnosed with biliary atresia).