Part II: Granulocyte-Colony Stimulating Factor Adjunct Therapy for Biliary Atresia
Part II: Granulocyte-Colony Stimulating Factor Adjunct Therapy for Biliary Atresia
The Investigators propose to test the hypothesis that GCSF enhances the clinical outcome of
 biliary atresia in a multi-institutional Phase 2 trial to prospectively evaluate the safety
 and efficacy of GCSF in each of the 2 groups of newly diagnosed BA patients: KBA (i.e.,
 Kasai-operated) or NoK (i.e., patients who did not undergo Kasai surgery). Subjects who
 participate in the trial will be followed for 2 years.
This is a prospective, randomized, multi-institutional trial in KBA and NoK subjects to be
 conducted under a Food and Drug Administration approved Investigational New Drug application.

 The KBA group is composed of just operated Kasai patients with intraoperative liver
 biopsy-confirmed BA. Their clinical characteristics have been described in the previously
 completed Phase 1 study under CR00005169 (ie. inclusion and exclusion criteria as described
 below)

 The NoK group will be composed of newly diagnosed BA patients, including the following:

 -  surgical patients in whom the Kasai was not performed for intraoperative technical
 reasons or due to advanced liver disease, who also have no option for rescue liver
 transplantation.

 -  Unoperated patients whose family refuses surgery or who are not operative candidates

 Having met the same inclusion and exclusion criteria as the Kasai KBS group,

 -  eligible KBA subjects will be randomized to GCSF vs. no-GCSF at the 10 ug/kg/d dose to
 be given subcutaneously for 3 consecutive daily doses on the third day following the
 Kasai procedure.

 -  eligible NoK subjects will be randomized to GCSF vs. no-GCSF at the 10 ug/kg/d dose to
 be given subcutaneously for 3 consecutive daily doses on the third day following
 diagnostic liver biopsy.
Inclusion criteria

 1. preliminary work up for cholestasis suspected or inconclusive diagnosis of BA.

 2. Serum Direct bilirubin > 2 mg/dl,GGT> 100 U/L

 3. Male or female infants with a gestational age> 36 weeks

 4. Admission weight > 2 kg

 5. Age > 14 days - 180 days at diagnosis

 6. For Kasai operated subjects, Type 3 or 4 anatomy of BA

 7. For Kasai operated subjects, cholangiogram (if performed) diagnostic of BA

 8. Liver biopsy supporting BA diagnosis

 Exclusion criteria

 1. Patients having access to liver transplantation for immediate liver failure

 2. Prior Kasai patients

 3. Major cardiac, renal, central nervous system (CNS) malformations

 4. Intracranial hemorrhage

 5. History of recent total parenteral nutrition (TPN) use within the last 2 weeks

 6. Gl tract obstruction

 For Kasai-operated subjects: Type 1 or 2 biliary atresia anatomy

 7. Current systemic infection

 8. WBC > 20,000 cells/uL

 9. Platelet count < 20,000 cells/uL or >1 million cells/uL

 10. Concurrent respiratory, metabolic, neurological, cardiovascular, metabolic, and renal
 illness

 11. Elevated serum creatinine > 1 mg/dL

 12. Purpura fulminans or unexplained vascular thrombosis