Toggle Main Menu Toggle Search

Open Access padlockePrints

Granulocyte colony-stimulating factor and autologous CD133-positive stem-cell therapy in liver cirrhosis (REALISTIC): an open-label, randomised, controlled phase 2 trial

Lookup NU author(s): Dr Deborah Stocken



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background Results of small-scale studies have suggested that stem-cell therapy is safe and effective in patients with liver cirrhosis, but no adequately powered randomised controlled trials have been done. We assessed the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) and haemopoietic stem-cell infusions in patients with liver cirrhosis. Methods This multicentre, open-label, randomised, controlled phase 2 trial was done in three UK hospitals and recruited patients with compensated liver cirrhosis and MELD scores of 11·0–15·5. Patients were randomly assigned (1:1:1) to receive standard care (control), treatment with subcutaneous G-CSF (lenograstim) 15 μg/kg for 5 days, or treatment with G-CSF for 5 days followed by leukapheresis and intravenous infusion of three doses of CD133-positive haemopoietic stem cells (0·2 × 106 cells per kg per infusion). Randomisation was done by Cancer Research UK Clinical Trials Unit staff with a minimisation algorithm that stratified by trial site and cause of liver disease. The coprimary outcomes were improvement in severity of liver disease (change in MELD) at 3 months and the trend of change in MELD score over time. Analyses were done in the modified intention-to-treat population, which included all patients who received at least one day of treatment. Safety was assessed on the basis of the treatment received. This trial was registered at Current Controlled Trials on Nov 18, 2009; ISRCTN, number 91288089; and the European Clinical Trials Database, number 2009-010335-41. Findings Between May 18, 2010, and Feb 26, 2015, 27 patients were randomly assigned to the standard care, 26 to the G-CSF group, and 28 to the G-CSF plus stem-cell infusion group. Median change in MELD from day 0 to 90 was −0·5 (IQR −1·5 to 1·1) in the standard care group, −0·5 (−1·7 to 0·5) in the G-CSF group, and −0·5 (−1·3 to 1·0) in the G-CSF plus stem-cell infusion group. We found no evidence of differences between the treatment groups and control group in the trends of MELD change over time (p=0·55 for the G-CSF group vs standard care and p=0·75 for the G-CSF plus stem-cell infusion group vs standard care). Serious adverse events were more frequent the in G-CSF and stem-cell infusion group (12 [43%] patients) than in the G-CSF (three [11%] patients) and standard care (three [12%] patients) groups. The most common serious adverse events were ascites (two patients in the G-CSF group and two patients in the G-CSF plus stem-cell infusion group, one of whom was admitted to hospital with ascites twice), sepsis (four patients in the G-CSF plus stem-cell infusion group), and encephalopathy (three patients in the G-CSF plus stem-cell infusion group, one of whom was admitted to hospital with encephalopathy twice). Three patients died, including one in the standard care group (variceal bleed) and two in the G-CSF and stem-cell infusion group (one myocardial infarction and one progressive liver disease). Interpretation G-CSF with or without haemopoietic stem-cell infusion did not improve liver dysfunction or fibrosis and might be associated with increased frequency of adverse events compared with standard care. Funding National Institute of Health Research, The Sir Jules Thorn Charitable Trust.

Publication metadata

Author(s): Newsome PN, Fox R, King AL, Barton D, Than N-N, Moore J, Corbett C, Townsend S, Thomas J, Guo K, Hull D, Beard HA, Thompson J, Atkinson A, Bienek C, McGowan N, Guha N, Campbell J, Hollyman D, Stocken D, Yap C, Forbes SJ

Publication type: Article

Publication status: Published

Journal: The Lancet Gastroenterology and Hepatology

Year: 2018

Volume: 3

Issue: 1

Pages: 25-36

Print publication date: 01/01/2018

Online publication date: 07/11/2017

Acceptance date: 02/04/2016

Date deposited: 08/01/2018

ISSN (print): 2468-1253

Publisher: Elsevier Ltd


DOI: 10.1016/S2468-1253(17)30326-6


Altmetrics provided by Altmetric


Funder referenceFunder name