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Background The acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis characterised by immune dysfunction and high mortality. Granulocyte-colony stimulating factor (G-CSF) mobilises immunomodulatory stem and immune cells and has been proposed as therapy for ACLF. We therefore conducted the first multicentre randomised trial. Methods In this prospective, controlled, open-label 2-armed study 176 patients with ACLF according to the EASL-CLIF criteria without malignancies or septic shock were randomised in 18 trial centres between 02/2016 and 01/2019 in a 1:1 ratio to receive either standard medical therapy (SMT) or SMT plus G-CSF (12 injections with 5µg/kg for 5days daily, then every 3 days). The primary efficacy endpoint was 90-day transplant free survival (TFS90). Results The 90-day transplant free survival was 34.1% in the G-CSF plus SMT group compared to 37.5% in the SMT group with a corresponding hazard ratio (HR) of 1.05 (95%CI 0.711; 1.551) (p=0.805). G.CSF had no effect on the 360-day transplant free survival HR of 0.998 [95%CI 0.697; 1.430 (p=0.992) or overall survival HR of 1.058 [95%CI 0.727; 1.548 (p=0.768). There was no improvement of the CLIF-C OF score (p=0.757), MELD score (p=0.884) or the rate of bacterial infections (p=0.251) with G-CSF therapy. In subgroups of patients without infections p=0.883, with alcohol related ACLF p=0.875, or with ACLF defined by the APASL criteria p=0.405 G-CSF also didn’t improve survival. There were 61 serious adverse events (SAE) reported in the G-CSF+SMT group and 57 SAEs in the SMT group including seven drug-related serious adverse reactions under G-CSF therapy. The study was prematurely terminated due to futility. Conclusion This interim analysis of the first multicentre trial reveals that G-CSF has no therapeutic effect in ACLF, which is in obvious contrast to the results from smaller clinical trials published previously. As a consequence, the study was prematurely terminated due to futility after conditional power calculation.
Engelmann et al. (Wed,) studied this question.