Granulocyte Colony-stimulating Factor Improves Innate Immunity in Pediatric Pretransplant Patients

Area of Science:

• Pediatric Gastroenterology and Hepatology
• Immunology and Inflammation
• Regenerative Medicine

Background:

• Children with decompensated cirrhosis (DC) awaiting liver transplantation (LT) face high risks of infection, mortality, and elevated Pediatric End-Stage Liver Disease (PELD) scores.
• Granulocyte colony-stimulating factor (G-CSF) has shown promise in improving outcomes for adult DC patients.
• This study explored G-CSF's efficacy in optimizing pre-transplant DC in children, focusing on its impact on cytokine activity and clinical parameters.

Purpose of the Study:

• To evaluate the effect of G-CSF therapy on cytokine profiles, liver function, and clinical outcomes in pediatric patients with decompensated cirrhosis awaiting liver transplantation.
• To assess G-CSF's impact on Pediatric End-Stage Liver Disease (PELD) scores, infection rates, and overall survival in this vulnerable patient population.

Main Methods:

• An open-label, randomized controlled trial involving pediatric DC patients (3 months-12 years) was conducted.
• The intervention group received standard medical treatment (SMT) plus 12 courses of subcutaneous G-CSF (5 μg/kg/day), while the control group received SMT alone.
• Key parameters assessed included PELD scores, cytokine levels (TNF-α, IL-10), hepatocyte growth factor (HGF), CD34+ mobilization, liver function tests (ALT), leukocyte and neutrophil counts, infection incidence, and survival.

Main Results:

• G-CSF treatment did not significantly alter PELD scores after 3 months.
• A significant decrease in TNF-α and increase in IL-10 and HGF were observed one month post-treatment (p < 0.001, p = 0.003).
• Significant improvements in alanine aminotransferase (ALT) levels (p = 0.038), leukocyte and neutrophil counts (p < 0.001), and a reduced incidence of sepsis (p = 0.04) were noted.

Conclusions:

• G-CSF therapy effectively reversed unfavorable cytokine profiles in pediatric DC, decreasing TNF-α and increasing IL-10.
• The observed increase in HGF suggests potential for hepatic regeneration, while the reduced sepsis incidence indicates improved clinical outcomes.
• Despite no significant change in PELD scores or survival, G-CSF demonstrates promise as an adjunctive therapy for optimizing pediatric liver transplant candidates.