Clinical trial NCT06708572: Evaluation of the Use of Granulocyte Colony Stimulating Factor (GCSF) in Post Kasai Type 3 Biliary Atresia
Official title: Evaluation of the Use of Granulocyte Colony Stimulating Factor (GCSF) in Post Kasai Type 3 Biliary Atresia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Granulocyte Colony-stimulating Factor
Biliary Atresia
Lead sponsor: National Liver Institute, Egypt
Sponsor class: OTHER
First posted: 2024-11-27
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Protocol of cohort study will be conducted on 40 infants with the final diagnosis of biliary atresia type 3 (supported by the liver histology and intra-operative findings) divided into two groups one of them is for GCSF after Kasai operation, and the other group will be without GCSF therapy and their data will be collected retrospectively.
Primary purpose: PREVENTION

Brief summary: The aim of the study is to evaluate the use of Granulocyte Colony Stimulating Factor (GCSF) on the clinical and biochemical outcome of type 3 biliary atresia post kasai.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of subjects with serum TBi (total bilirubin) ≥ 2 mg/dL at 3 months.
timeFrame: baseline
Secondary outcomes:
measure: Differences in the proportion of subjects with cholangitis at 6 months.
timeFrame: base line
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: National Liver Institute
state: Menofia Governorate
Study officials:
References:
citation: Bezerra JA, Wells RG, Mack CL, Karpen SJ, Hoofnagle JH, Doo E, Sokol RJ. Biliary Atresia: Clinical and Research Challenges for the Twenty-First Century. Hepatology. 2018 Sep;68(3):1163-1173. doi: 10.1002/hep.29905.
citation: Overi D, Carpino G, Cardinale V, Franchitto A, Safarikia S, Onori P, Alvaro D, Gaudio E. Contribution of Resident Stem Cells to Liver and Biliary Tree Regeneration in Human Diseases. Int J Mol Sci. 2018 Sep 25;19(10):2917. doi: 10.3390/ijms19102917.
citation: Corrado MM, Mack CL. Diagnostic Tools for Early Detection of Biliary Atresia: Is a Newborn Screen Attainable? Clin Liver Dis (Hoboken). 2022 Jan 24;19(1):25-28. doi: 10.1002/cld.1165. eCollection 2022 Jan.