Evaluation of the Use of Granulocyte Colony Stimulating Factor (GCSF) in Post Kasai Type 3 Biliary Atresia

Biliary atresia (BA) is a devastating disease manifest early in infancy characterized by bile duct injury and extrahepatic biliary obstruction, leading to cirrhosis in the majority of infants.

Although BA is a rare disease, occurring in ~1 in 5600 to 1 in 18,000 infants worldwide, it is considered the most common indication for liver transplantation in children.

However, despite a 50-60% rate of initial jaundice clearance, liver transplantation by 2 years of age is necessary for long term survival in many of the post-Kasai patients.

GCSF cytokine that stimulates neutrophil and hematopoietic stem cell (HSC) production and mobilization from the bone marrow, and has served as a complementary agent to bone marrow stem cell therapy for patients with congenital or acquired diseases of bone marrow suppression.

Granulocyte colony-stimulating factor (G-CSF) mobilizes CD34+(cluster of differentiation34) cells, these CD34+ cells increase hepatocyte growth factor inducing the proliferation of hepatic progenitor cells within 7 days.

In experimental liver diseases of toxin-induced or bile duct ligation-induced liver injury, GCSF-based stem cell therapy has the same effects as direct HSC transplantation on improving liver regeneration and suppressing the inflammatory and fibrotic responses to hepatic injury. The cellular and molecular mechanisms are unknown but are postulated to be derived from the many paracrine actions of GCSF.

Inclusion criteria

• Infants with initial diagnosis of biliary atresia with biliary atresia score > 23.927 will be allocated for Kasai porto-enterostomy with intra-operative cholangiogram reaching type 3 biliary atresia anatomy as a final diagnosis.

Exclusion criteria

• Major cardiac, renal, pulmonary, neurological malformations or illnesses.
• Hemoglobinopathies, such as sickle cell anemia
• Active systemic infection.
• White blood cell count > 20,000 cells/mm3.
• Platelet count < 40,000 cells/mm3 or ≥ 800,000 cells/mm3.
• Purpura fulminans or unexplained vascular thrombotic conditions.