Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure

Gastroenterology. 2012 Mar;142(3):505-512.e1. doi: 10.1053/j.gastro.2011.11.027. Epub 2011 Nov 23.

Abstract

Background & aims: Acute-on-chronic liver failure (ACLF) develops in patients with chronic liver disease and has high mortality. Mobilization of bone marrow-derived stem cells with granulocyte colony-stimulating factor (G-CSF) could promote hepatic regeneration.

Methods: Consecutive patients with ACLF were randomly assigned to groups given 5 μg/kg G-CSF subcutaneously (12 doses; group A, n = 23) or placebo (group B, n = 24) plus standard medical therapy. We assessed survival until day 60; Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), and Sequential Organ Failure Assessment (SOFA) scores; and the development of other related complications.

Results: After 1 week of treatment, group A had higher median leukocyte and neutrophil counts than group B (P < .001). Sixteen patients in group A (69.6%) and 7 in group B (29%) survived; the actuarial probability of survival at day 60 was 66% versus 26%, respectively (P = .001). Treatment with G-CSF also reduced CTP scores in group A by a median of 33.3% compared with an increase of 7.1% in group B (P = .001), along with MELD (median reduction of 15.3% compared with an increase of 11.7% in group B; P = .008) and SOFA scores (median reduction of 50% compared with an increase of 50% in group B; P = .001). The percentages of patients who developed hepatorenal syndrome, hepatic encephalopathy, or sepsis were lower in group A than in group B (19% vs 71% [P = .0002], 19% vs 66% [P = .001], and 14% vs 41% [P = .04], respectively). After 1 month of treatment, G-CSF increased the number of CD34(+) cells in the liver (by 45% compared with 27.5% in group B; P = .01).

Conclusions: G-CSF therapy more than doubles the percentage of patients with ACLF who survive for 2 months; it also significantly reduces CTP, MELD, and SOFA scores and prevents the development of sepsis, hepatorenal syndrome, and hepatic encephalopathy.

Trial registration: ClinicalTrials.gov NCT01036932.

Publication types

  • Randomized Controlled Trial
  • Video-Audio Media

MeSH terms

  • Adult
  • Aged
  • Antigens, CD34 / metabolism*
  • Cell Movement / drug effects*
  • Chi-Square Distribution
  • End Stage Liver Disease / diagnosis
  • End Stage Liver Disease / drug therapy*
  • End Stage Liver Disease / immunology
  • End Stage Liver Disease / mortality
  • Female
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • India
  • Kaplan-Meier Estimate
  • Liver / drug effects*
  • Liver / immunology
  • Liver / pathology
  • Liver Failure, Acute / diagnosis
  • Liver Failure, Acute / drug therapy*
  • Liver Failure, Acute / immunology
  • Liver Failure, Acute / mortality
  • Liver Regeneration / drug effects
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Stem Cells / drug effects*
  • Stem Cells / immunology
  • Stem Cells / pathology
  • Survival Rate
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD34
  • Granulocyte Colony-Stimulating Factor

Associated data

  • ClinicalTrials.gov/NCT01036932