Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-7-10
pubmed:databankReference
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1527-3350
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18537187-Adult, pubmed-meshheading:18537187-Aged, pubmed-meshheading:18537187-Antigens, CD34, pubmed-meshheading:18537187-Cell Proliferation, pubmed-meshheading:18537187-Cytokines, pubmed-meshheading:18537187-Fatty Liver, Alcoholic, pubmed-meshheading:18537187-Female, pubmed-meshheading:18537187-Follow-Up Studies, pubmed-meshheading:18537187-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:18537187-Hepatocyte Growth Factor, pubmed-meshheading:18537187-Humans, pubmed-meshheading:18537187-Immunologic Techniques, pubmed-meshheading:18537187-Keratin-7, pubmed-meshheading:18537187-Ki-67 Antigen, pubmed-meshheading:18537187-Liver, pubmed-meshheading:18537187-Male, pubmed-meshheading:18537187-Middle Aged, pubmed-meshheading:18537187-Neutrophils, pubmed-meshheading:18537187-Recombinant Proteins, pubmed-meshheading:18537187-Staining and Labeling, pubmed-meshheading:18537187-Stem Cells
pubmed:year
2008
pubmed:articleTitle
Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial.
pubmed:affiliation
Department of Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland. laurent.spahr@hcuge.ch
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Clinical Trial, Phase II