Semin Liver Dis 2021; 41(03): 298-307
DOI: 10.1055/s-0041-1723034
Review Article

The Current Status of Granulocyte-Colony Stimulating Factor to Treat Acute-on-Chronic Liver Failure

Cornelius Engelmann
1  Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, United Kingdom
2  Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
3  Division of Hepatology and Gastroenterology, Department of Medical, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany
,
Vincent Di Martino
4  Service d'Hépatologie et de Soins Intensifs Digestifs, Hôpital Jean Minjoz, 25000 Besançon, France
,
Annarein J.C. Kerbert
1  Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, United Kingdom
,
Delphine Weil-Verhoeven
4  Service d'Hépatologie et de Soins Intensifs Digestifs, Hôpital Jean Minjoz, 25000 Besançon, France
,
Niklas Friedemann Aehling
2  Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
,
Adam Herber
2  Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
,
Thierry Thévenot
4  Service d'Hépatologie et de Soins Intensifs Digestifs, Hôpital Jean Minjoz, 25000 Besançon, France
,
Thomas Berg
2  Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
› Author Affiliations
Funding The authors received no funding for the review.

Abstract

Patients with acute-on-chronic liver failure (ACLF) have a devastating prognosis and therapeutic options are limited. Granulocyte-colony stimulating factor (G-CSF) mobilizes immune and stem cells and possess immune-modulatory and proregenerative capacities. In this review, we aim to define the current evidence for the treatment with G-CSF in end-stage liver disease. Several smaller clinical trials in patients with different severity grades of end-stage liver disease have shown that G-CSF improves survival and reduces the rate of complications. Adequately powered multicenter European trials could not confirm these beneficial effects. In mouse models of ACLF, G-CSF increased the toll-like receptor (TLR)-mediated inflammatory response which led to an increase in mortality. Adding a TLR4 signaling inhibitor allowed G-CSF to unfold its proregenerative properties in these ACLF models. These data suggest that G-CSF requires a noninflammatory environment to exert its protective properties.

Disclosures

C.E., T.B., N.F.A., A.H., and A.J.C.K. were involved in performing the GRAFT study and a project evaluating G-CSF + TLR4 inhibition as a therapy for acute-on-chronic liver failure which are both discussed in that paper.


All other authors have nothing to disclose.




Publication History

Publication Date:
15 May 2021 (online)

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