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

J Clin Exp Hepatol. 2024 Mar-Apr;14(2):101282. doi: 10.1016/j.jceh.2023.09.003. Epub 2023 Sep 15.

Abstract

Background: Children with decompensated cirrhosis (DC) awaiting LT suffer from infection linked to high pediatric end-stage liver disease (PELD) scores and mortality. Granulocyte colony-stimulating factor (G-CSF) therapy has shown promising results in adult DC. Our study investigated G-CSF as an optimizing treatment for pre-transplant DC, exploring its effect on cytokine activity.

Methods: An open-label, randomized controlled trial included DC patients aged 3 months-12 years. The intervention group (n=26) received 12 G-CSF courses injected subcutaneously (5 μg/kg/day) plus DC standard medical treatment (SMT). The control group (n = 24) received SMT. We obtained PELD scores, tumor necrosis factor (TNF)-α, interleukin (IL)-10, hepatocyte growth factor (HGF), CD34+ mobilization, liver function, leukocyte and neutrophil counts. Infection and side effects were documented.

Results: There was no significant difference in PELD scores between the groups after 3 months G-CSF treatment. Decreased TNF-α (p < 0.001) and increased IL-10 and HGF (p = 0.003 for both markers) were shown 1 month following G-CSF treatment. Alanine aminotransferase (ALT) levels improved significantly (p = 0.038). Significant increase in leucocyte and neutrophil counts (p < 0.001) and a lower incidence of sepsis (p = 0.04) were shown after intervention. There was no significant difference in survival (p = 0.372).

Conclusion: Following 3 months of G-CSF treatment, PELD scores did not show significant improvement. G-CSF reversed the cytokine profiles in DC, resulting in reduced TNF-α and increased IL-10. HGF significantly improved, indicating hepatic regeneration. Significantly decreased occurrence of sepsis following G-CSF treatment indicated improved clinical outcome.

Keywords: G-CSF; cytokine; pediatric cirrhosis.