Engelmann, Cornelius, Herber, Adam, Franke, Annegret, Bruns, Tony ORCID: 0000-0002-5576-6914, Reuken, Philipp, Schiefke, Ingolf, Zipprich, Alexander, Zeuzem, Stefan, Goeser, Tobias, Canbay, Ali, Berg, Christoph, Trebicka, Jonel, Uschner, Frank E., Chang, Johannes, Mueller, Tobias ORCID: 0000-0003-3426-5421, Aehling, Niklas, Schmelzle, Moritz, Splith, Katrin, Lammert, Frank, Lange, Christian M., Sarrazin, Christoph, Trautwein, Christian, Manns, Michael, Haeussinger, Dieter, Pfeiffenberger, Jan, Galle, Peter R., Schmiedeknecht, Anett and Berg, Thomas (2021). Granulocyte-colony stimulating factor (G-CSF) to treat acute-on- chronic liver failure: A multicenter randomized trial (GRAFT study). J. Hepatol., 75 (6). S. 1346 - 1356. AMSTERDAM: ELSEVIER. ISSN 1600-0641

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Abstract

Background & Aims: Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. Methods: In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 mu g/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary effi- cacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. Results: Patients treated with G-CSF had a 90-day transplant free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711-1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697-1.430; p = 0.992 and HR 1.058; 95% CI 0.727-1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the GCSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. Conclusions: In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. ClinicalTrials.gov number: NCT02669680 Lay summary: Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Engelmann, CorneliusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herber, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, AnnegretUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, TonyUNSPECIFIEDorcid.org/0000-0002-5576-6914UNSPECIFIED
Reuken, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schiefke, IngolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zipprich, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeuzem, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goeser, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canbay, AliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berg, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trebicka, JonelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uschner, Frank E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chang, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, TobiasUNSPECIFIEDorcid.org/0000-0003-3426-5421UNSPECIFIED
Aehling, NiklasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmelzle, MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Splith, KatrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lammert, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lange, Christian M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sarrazin, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trautwein, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manns, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haeussinger, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfeiffenberger, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galle, Peter R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmiedeknecht, AnettUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berg, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-605285
DOI: 10.1016/j.jhep.2021.07.033
Journal or Publication Title: J. Hepatol.
Volume: 75
Number: 6
Page Range: S. 1346 - 1356
Date: 2021
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1600-0641
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IMPROVES SURVIVAL; CELLS; DYSFUNCTION; HEPATITIS; MIGRATION; THERAPYMultiple languages
Gastroenterology & HepatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60528

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