title: Granulocyte-colony stimulating factor for acute-on-chronic liver failure: systematic review and meta-analysis.
abstract: Acute-on-chronic liver failure (ACLF) is associated with increased short and long-term mortality. Animal models of liver failure have demonstrated that granulocyte-colony stimulating factor (G-CSF) accelerates the liver regeneration process and improves survival. However, clinical evidence regarding the use of G-CSF in ACLF remains scarce. The aim of this study was to assess the benefits and harms of G-CSF in patients with acute-on-chronic liver failure. An electronic search was made in The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS up to November 2013. Randomized clinical trials comparing the use of any regimen of G-CSF against placebo or no intervention in patients with ACLF were included. Primary outcomes included overal mortality, mortality due multi-organ failure, and adverse events. Relative risk (RR) and mean difference (MD) were used. Two trials involving 102 patients were included. A significant reduction in short-term overall mortality was observed in patients receiving G-CSF compared to controls (RR 0.56; 95%CI 0.39,0.80). G-CSF failed to reduce mortality secondary to gastrointestinal bleeding (RR 1.45; 95%CI 0.50, 4.27). Adverse effects reported included: fever, rash, herpes zoster, headache and nausea. In conclusion, the use of G-CSF for the treatment of patients with ACLF significantly reduced short-term mortality. While the evidence is still limited, the apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable.
authors.affiliation: Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Norberto C
authors.initials: NC
authors.lastname: Chavez-Tapia
authors.affiliation: National Institute of Public Health. Cuernavaca, Mexico City, Mexico.
authors.forename: Indira
authors.initials: I
authors.lastname: Mendiola-Pastrana
authors.affiliation: Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Ornelas-Arroyo
authors.affiliation: National Institute of Public Health. Cuernavaca, Mexico City, Mexico.
authors.forename: Camilo
authors.initials: C
authors.lastname: Noreña-Herrera
authors.affiliation: National Institute of Public Health. Cuernavaca, Mexico City, Mexico.
authors.forename: Desiree
authors.initials: D
authors.lastname: Vidaña-Perez
authors.affiliation: National Institute of Public Health. Cuernavaca, Mexico City, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Delgado-Sanchez
authors.affiliation: Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Misael
authors.initials: M
authors.lastname: Uribe
authors.affiliation: National Institute of Public Health. Cuernavaca, Mexico City, Mexico.
authors.forename: Tonatiuh
authors.initials: T
authors.lastname: Barrientos-Gutierrez
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002423:Cause of Death; D016009:Chi-Square Distribution; D018450:Disease Progression; D000069585:Filgrastim / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009102:Multiple Organ Failure / Q000401:mortality; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000069585:Filgrastim