G-CSF Monotherapy Does Not Improve Outcomes in Acute-on-Chronic Liver Failure

Investigators assessed the safety and efficacy of granulocyte-colony stimulating factor in the treatment of patients with acute-on-chronic liver failure.

Granulocyte-colony stimulating factor (G-CSF) does not improve survival or other clinical endpoints in patients with acute-on-chronic liver failure (ACLF), according to a study in the Journal of Hepatology.

The randomized controlled trial recruited patients with ACLF from 18 German tertiary centers between March 2016 and April 2019. Participants were randomly assigned 1:1 to receive either G-CSF (5 µg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) or SMT alone.

The patients were followed up for 360 days or until premature study termination. The primary endpoint was transplant-free survival 90 days after inclusion.

The mean age was 54.4±10.2 years for the G-CSF+SMT group (56.8% men) and 57.1±9.6 years for the SMT group (69.3% men).

The primary endpoint was achieved in 54 patients (61.4%) in the G-CSF+SMT group and 51 patients (58.0%) in the SMT group. The hazard ratio (HR) for risk for death or transplantation after treatment with G-CSF was 1.05 (95% CI, 0.711-1.551; P =.805).

The median transplant-free survival was 35 days (95% CI, 19.8-50.2) in the G-CSF+SMT group and 34 days (95% CI, 9.9-58.1) in the SMT group. Overall survival (HR, 1.058; 95% CI, 0.727-1.548; P =.768) and 360-day transplant-free survival (HR, 0.998; 95% CI, 0.697-1.430; P =.992) were not statistically different between the 2 groups in the intention-to-treat cohort.

Multivariate Cox regression analysis showed that age (HR, 1.043; 95% CI, 1.019-1.066; P <.001), ACLF severity grade at baseline (HR, 2.249; 95% CI, 1.703-2.970; P <.001), and white blood cell count at baseline (HR, 1.044; 95% CI, 1.02-1.066; P <.001) were risk factors for mortality.

In the G-CSF+SMT group, 80 patients reported 403 adverse events, and 78 patients in the SMT group reported 354 adverse events. In addition, 61 serious adverse events (SAEs) occurred in 54 patients from the G-CSF+SMT group, and 57 SAEs occurred in 47 patients from the SMT group, including 37 and 36 deaths, respectively. ACLF was the leading cause of death in the G-CSF+SMT group (n=17/37 [46%]) and in the SMT group (n=16/36 [44%]; P =1.0).

Among several limitations, patient recruitment was prematurely terminated due to futility after performance of conditional power analyses in parallel to the planned interim analysis. Additionally, no data were provided regarding the mode of action of G-CSF in ACLF.

“This multicenter randomized study confirms the dismal prognosis of patients with ACLF and failed to demonstrate any beneficial effect of treating this condition with G-CSF monotherapy,” stated the investigators. “G-CSF was associated with drug-related serious adverse reactions and should not be used outside clinical trials for the treatment of ACLF,” they concluded.

Disclosure: Some of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.


Engelmann C, Herber A, Franke A, et al. Granulocyte-colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: a multicenter randomized trial (GRAFT study). J Hepatol. 2021;75(6):1346-1354. doi: 10.1016/j.jhep.2021.07.033