2015, Number 5
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Ann Hepatol 2015; 14 (5)
Granulocyte-colony stimulating factor for acute-on-chronic liver failure: systematic review and meta-analysis
Chavez-Tapia NC, Mendiola-Pastrana I, Ornelas-Arroyo VJ, Noreña-Herrera C, Vidaña-Perez D, Delgado-Sanchez G, Uribe M, Barrientos-Gutierrez T
Language: English
References: 37
Page: 631-641
PDF size: 138.56 Kb.
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.
REFERENCES
Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, de Silva HJ, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2009; 3: 269-82.
Olson J.C, Kamath P.S. Acute-on-chronic liver failure: concept, natural history, and prognosis. Curr Opin Crit Care 2011; 17: 165-9.
Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013; 144: 1426-37, 1437 e1-9.
Katoonizadeh A, Laleman W, Verslype C, Wilmer A, Maleux G, Roskams T, Nevens F. Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 2010; 59: 1561-9.
Garg H, Kumar A, Garg V, Sharma P, Sharms BC, Sarin SK. Clinical profile and predictors of mortality in patients of acuteon- chronic liver failure. Dig Liver Dis 2012; 44: 166-71.
Sen S, Williams R, Jalan R. The pathophysiological basis of acute-on-chronic liver failure. Liver 2002; 22(Suppl. 2): 5-13.
Cordoba J, Ventura-Cots M, Simón-Talero M, Amorós A, Pavesi M, Vilstrup H, Angeli P, et al. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-onchronic liver failure (ACLF). J Hepatol 2014; 60: 275-81.
Wlodzimirow KA, Eslami S, Abu-Hanna A, Nieuwoudt M, Chamuleau RA. A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality. Liver Int 2013; 33: 40-52.
Jalan R, Gines P, Olson JC, Mookerjee RP, Moreau R, Garcia- Tsao G, Arroyo V, et al. Acute-on chronic liver failure. J Hepatol 2012; 57: 1336-48.
Laleman W, Verbeke L, Meersseman P, Wauters J, van Pelt J, Cassiman D, Wilmer A, et al. Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions. Expert Rev Gastroenterol Hepatol 2011; 5: 523-37.
Houston AC, Stevens LA, Cour V. Pharmacokinetics of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in healthy male volunteers. Br J Clin Pharmacol 1999; 47: 279-84.
D’Souza A, Jaiyesimi I, Trainor L, Venuturumili. Granulocyte colony-stimulating factor administration: adverse events. Transfus Med Rev 2008; 22: 280-90.
Piscaglia A.C, Shupe TD, Oh SH, Gasbarrini A, Petersen BE. Granulocyte-colony stimulating factor promotes liver repair and induces oval cell migration and proliferation in rats. Gastroenterology 2007; 133: 619-31.
Yannaki E, Athanasiou E, Xagorari A, Constantinou V, Batsis I, Kaloyannidis P, Proya E, et al. G-CSF-primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs. Exp Hematol 2005; 33: 108-19.
Spahr L, Lambert JF, Rubbia-Brandt L, Chalandon Y, Frossard JL, Giostra E, Hadengue A. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Hepatology 2008; 48: 221-9.
Gaia S, Smedile A, Omedè P, Olivero A, Sanavio F, Balzola F, Ottobrelli A. Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease. J Hepatol 2006; 45: 13-9.
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) adopts Consolidated Guideline on Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Products for Human Use. Int Dig Health Legis 1997; 48: 231-4.
Higgins JPT, Green S, and Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions. Chichester, England ; Hoboken, NJ: Wiley-Blackwell; 2005, p. 649.
Di Campli C, Zocco MA, Saulnier N, Grieco A, Rapaccini G, Addolorato G, Rumi C, et al. Safety and efficacy profile of G-CSF therapy in patients with acute on chronic liver failure. Dig Liver Dis 2007; 39: 1071-6.
Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC, Sakhuja P, et al. Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology 2012; 142: 505-512 e1.
Duan XZ, Liu FF, Tong JJ, Yang HZ, Chen J, Liu XY, Mao YL, et al. Granulocyte-colony stimulating factor therapy improves survival in patients with hepatitis B virus-associated acute-on-chronic liver failure. World J Gastroenterol 2013; 19: 1104-10.
Morstyn G, Lieschke GJ, Cebon J, Dührsen U, Villeval JL, Sheridan W, McGrath K, et al. Early clinical trials with colony- stimulating factors. Cancer Invest 1989; 7: 443-56.
Sylvester RK. Clinical applications of colony-stimulating factors: a historical perspective. Am J Health Syst Pharm 2002; 59: S6-S12.
Kuwabara T, Kobayashi S, Sugiyama Y. Pharmacokinetics and pharmacodynamics of a recombinant human granulocyte colony-stimulating factor. Drug Metab Rev 1996; 28: 625-58.
Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood 1991; 78: 2791-808.
Quintana-Bustamante O, Alvarez-Barrientos A, Kofman AV, Fabregat I, Bueren JA, Theise ND, Segovia JC. Hematopoietic mobilization in mice increases the presence of bone marrow-derived hepatocytes via in vivo cell fusion. Hepatology 2006; 43: 108-16.
Zhang L, Kang W, Lei Y, Han Q, Zhang G, Lv Y, Li Z, et al. Granulocyte colony-stimulating factor treatment ameliorates liver injury and improves survival in rats with D-galactosamine- induced acute liver failure. Toxicol Lett 2011; 204: 92-9.
Li N, Zhang L, Li H, Fang B. Administration of granulocyte colony-stimulating factor ameliorates radiation-induced hepatic fibrosis in mice. Transplant Proc 2010; 42: 3833-9.
Maiwal R, Kumar A, Sarin SK. Liver regeneration during acute-on-chronic liver failure using growth factors: in vivo or ex vivo indulgence of bone marrow? Gastroenterology 2013; 145: 901-4.
Bird TG, Lorenzini S, Forbes SJ. Activation of stem cells in hepatic diseases. Cell Tissue Res 2008; 331: 283-300.
Meng F, Francis H, Glaser S, Han Y, DeMorrow S, Stokes A, Staloch D, et al. Role of stem cell factor and granulocyte colony-stimulating factor in remodeling during liver regeneration. Hepatology 2012; 55: 209-21.
Masson S, Harrison DJ, Plevris JN, Newsome PN. Potential of hematopoietic stem cell therapy in hepatology: a critical review. Stem Cells 2004; 22: 897-907.
Thorgeirsson SS, Grisham JW. Hematopoietic cells as hepatocyte stem cells: a critical review of the evidence. Hepatology 2006; 43: 2-8.
Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002; 297: 2256-9.
Rolando N, Clapperton M, Wade J, Panetsos G, Mufti G, Williams R. Granulocyte colony-stimulating factor improves function of neutrophils from patients with acute liver failure. Eur J Gastroenterol Hepatol 2000; 12: 1135-40.
Rolando N, Clapperton M, Wade J, Wendon J. Administering granulocyte colony-stimulating factor to acute liver failure patients corrects neutrophil defects. Eur J Gastroenterol Hepatol 2000; 12: 1323-8.
Zamora Nava LE, Aguirre Valadez J, Chávez-Tapia NC, Torre A. Acute-on-chronic liver failure: a review. Ther Clin Risk Manag 2014; 10: 295-303.