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Scientific article
English

Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial

Published inHepatology, vol. 48, no. 1, p. 221-229
Publication date2008
Abstract

Liver failure is the major cause of death in alcoholic steatohepatitis (ASH). In experimental hepatitis, granulocyte-colony stimulating factor (G-CSF) mobilizes hematopoietic stem cells, induces liver regeneration, and improves survival. We studied the short-term effects of G-CSF on CD34+ stem cell mobilization, liver cell proliferation, and liver function in patients with ASH. Twenty-four patients (mean age 54 years) with alcoholic cirrhosis [Child-Turcotte-Pugh score 10 (7-12)] and concomitant biopsy-proven ASH [Maddrey score 36 (21-60)] were randomized to standard care associated with 5 days of G-CSF (10 microg/kg/day, group A, n = 13) or standard care alone (group B, n = 11). Serial measurement of CD34+ cells, liver tests, cytokines [hepatocyte growth factor (HGF); tumor necrosis factor alpha; tumor necrosis factor-R1; interleukin-6; alfa-fetoprotein], and (13)C-aminopyrine breath tests were performed. Proliferating hepatic progenitor cells [HPC; double immunostaining (Ki67/cytokeratin 7)], histology, and neutrophils were assessed on baseline and day 7 biopsies. Abstinent alcoholic patients with cirrhosis served as controls for immunohistochemistry. G-CSF was well tolerated. At day 7, both CD34+ cells (+747% versus -6%, P < 0.003), and HGF (+212% versus -7%, P < 0.03) increased in group A but not in group B. Cytokines and aminopyrine breath test changes were similar between groups. On repeat biopsy, a >50% increase in proliferating HPC was more frequent in group A than in group B (11 versus 2, P < 0.003). Changes in Ki67+/cytokeratin 7+ cells correlated with changes in CD34+ cells (r = 0.65, P < 0.03). Neutrophils and histological changes were similar in both groups. CONCLUSION: G-CSF mobilizes CD34+ cells, increases HGF, and induces HPC to proliferate within 7 days of administration. Larger trials would be required to determine whether these changes translate into improved liver function.

Keywords
  • Adult
  • Aged
  • Antigens, CD34/metabolism
  • Cell Proliferation/drug effects
  • Cytokines/blood
  • Fatty Liver, Alcoholic/drug therapy/metabolism/pathology/physiopathology
  • Female
  • Filgrastim/therapeutic use
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor/adverse effects/therapeutic use
  • Hepatocyte Growth Factor/metabolism
  • Humans
  • Immunologic Techniques
  • Keratin-7/metabolism
  • Ki-67 Antigen/metabolism
  • Liver/immunology/metabolism/pathology/physiopathology
  • Male
  • Middle Aged
  • Neutrophils/pathology
  • Staining and Labeling
  • Stem Cells/pathology
Citation (ISO format)
SPAHR, Laurent et al. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. In: Hepatology, 2008, vol. 48, n° 1, p. 221–229. doi: 10.1002/hep.22317
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Article (Accepted version)
accessLevelRestricted
Identifiers
ISSN of the journal1527-3350
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