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 g/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 ␣; 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. (HEPATOLOGY 2008;48:221-229.)A lcoholic steatohepatitis (ASH) carries a poor short-term prognosis, with liver failure resulting from both acute liver injury and from chronic liver disease. Elevated proinflammatory cytokines during ASH have prognostic significance. 2 Both anti-inflammatory and liver regeneration mechanisms participate in the repair of ASHdependent liver damage. Although corticosteroids decrease proinflammatory cytokines and bring a clear survival benefit in severe, biopsy-proven ASH, 3 regeneration is also crucial to restore liver function. Hepatocellular injury is believed to trigger proliferation of the remaining mature hepatocytes. Ductular proliferation is thought to be a source of progenitor cells (at the interface between portal tracts and the liver lobule) that can give rise to hepatocyte and biliary cells. However, regeneration processes are impaired in cirrhosis, 5 and the influence on liver cell proliferation of alcohol itself 6 or the presence of steatohepatitis 7 remains unclear.