title: Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure.
abstract: OBJECTIVE
  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.
authors: Department of Gastroenterology, GB Pant Hospital, New Delhi, India.
authors: Vishal
authors: V
authors: Garg
authors: Hitendra
authors: H
authors: Garg
authors: Arshi
authors: A
authors: Khan
authors: Nirupama
authors: N
authors: Trehanpati
authors: Ashish
authors: A
authors: Kumar
authors: Barjesh Chander
authors: BC
authors: Sharma
authors: Puja
authors: P
authors: Sakhuja
authors: Shiv Kumar
authors: SK
authors: Sarin
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D016009:Chi-Square Distribution; D058625:End Stage Liver Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007194:India; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D017114:Liver Failure, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor