GCSF Adjunct Therapy for Biliary Atresia

In BA, neonatal fibrous obliteration of the biliary tract obstructs biliary drainage and
promotes biliary fibrosis. BA is the leading cause of pediatric chronic end-stage liver
disease and pediatric liver transplantation. Relief of cholestasis by the Kasai
portoenterostomy is only partly successful with continued progression of fibrosis to hepatic
insufficiency and, for long term survival, with eventual need for liver transplantation in
the majority of the patients. In animal models of liver injury, GCSF enhances hematopoietic
stem cell HSC mobilization and engraftment in the liver with associated improved liver repair
response and attenuated hepatic necrosis and fibrosis. Randomized controlled trials of GCSF
intervention for chronic liver failure in adult patients with acute hepatic decompensation
showed improved short-term survival and hepatic indices such the model for end-stage liver
disease (MELD) scores.

The Investigators propose that post Kasai GCSF therapy attenuates biliary fibrosis and
progression to cirrhosis. The objectives are meant to demonstrate that Kasai-GCSF sequential
therapy improves biliary drainage, and delays the progression of hepatic insufficiency.
Toward this goal, Investigators will first evaluate in post Kasai subjects the maximum
tolerated dose of GCSF in mobilizing circulating CD34+ hematopoietic stem cells, with the
limiting dose based on GCSF-related severe adverse effects. A one-month safety of GCSF will
be tested with the 2 standard doses of 5 ug/kg/d and 10 ug/kg/d.

Inclusion Criteria:

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

2. Gestational Age > 36wks

3. Weight > 2 Kg

4. Age >-2 weeks-<180 days at diagnosis

5. Serum Direct Bilirubin > 2 mg/dL GGT > 100 U/L

6. Kasai operated patients for Type 3 or 4 anatomy of BA

7. Cholangiogram/porta hepatis findings diagnostic of BA

8. Liver biopsy supporting BA diagnosis

Exclusion Criteria:

1. Having access to liver transplantation for immediate Kasai failure

2. Prior Kasai patients

3. Major cardiac, renal, CNS malformations with poor prognosis

4. Intracranial hemorrhage

5. History of recent TPN use within the last 2 weeks of surgery

6. GI tract obstruction

7. Laparoscopic Kasai repair