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

Spahr, Laurent
Lambert, Jean-François
Published in Hepatology. 2008, vol. 48, no. 1, p. 221-9
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 AdultAgedAntigens, CD34/metabolismCell Proliferation/drug effectsCytokines/bloodFatty Liver, Alcoholic/drug therapy/metabolism/pathology/physiopathologyFemaleFilgrastim/therapeutic useFollow-Up StudiesGranulocyte Colony-Stimulating Factor/adverse effects/therapeutic useHepatocyte Growth Factor/metabolismHumansImmunologic TechniquesKeratin-7/metabolismKi-67 Antigen/metabolismLiver/immunology/metabolism/pathology/physiopathologyMaleMiddle AgedNeutrophils/pathologyStaining and LabelingStem Cells/pathology
PMID: 18537187
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Research groups Métastases du foie (657)
Physiopathologie de la pancréatite aiguë (601)
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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. 221-9. doi: 10.1002/hep.22317 https://archive-ouverte.unige.ch/unige:1134

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Deposited on : 2009-03-13

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