The Efficacy and Safety of Granulocyte Colony-stimulating Factor in the Treatment of Acute-on-chronic Liver Failure: a Systematic Review and Meta-analysis

Bo Qiu, Jia Xu Liang, Manuel Romero Gómez


The safety and efficacy of granulocyte-colony stimulating factor (G-CSF) for the treatment of acute-on-chronic liver failure (ACLF) remain controversial. This meta-analysis aimed to evaluate the effectiveness and safety of G-CSF in treating ACLF.


Acute-on-chronic liver failure (ACLF) is a severe and life-threatening condition characterized by an acute deterioration of liver function in patients with pre-existing chronic liver disease [1]. ACLF can result from various etiologies, including viral hepatitis, alcohol-related liver disease, non-alcoholic fatty liver disease, and autoimmune liver disease [2]. It is characterized by severe systemic inflammation, organ failure, and poor prognosis [3,4]. The mortality exceeded 30% at 28 days and 63% at 90 days [5,6]. The only recommended treatment option is liver transplantation, but the scarcity and high cost of donor organs limit its use.

Materials and method

Two independent investigators (B. Q and JX. L) conducted a comprehensive search of the PubMed, Cochrane Library, and Embase to identify relevant studies published up to March 2023. The search strategy involved using MeSH terms and keywords, including (“granulocyte-colony stimulating factor” or “G-CSF”) and (“acute-on-chronic liver failure” or “ACLF" or “liver failure” or “Hepatic failure” or “severe hepatitis” or “Fulminant hepatitis”). No restrictions were placed on article type or additional filters during the search. A manual search was also conducted by reviewing the references of original articles and relevant review articles. The results were collected independently by the two investigators.


Out of the 563 articles identified through searches of the Cochrane Library, PubMed, Embase, and references, 10 studies including a total of 603 participants were ultimately included in our meta-analysis [10,11,14,15,18–23]. A flowchart detailing the study identification and selection process is presented in Fig 1. Of the 10 studies analyzed, five were conducted in India [11,15,20–22], two in China [10,23], two in Bangladesh [14,19], and one in Germany [18]. The main characteristics of each study are summarized in Table 1. Prior to data analysis and synthesis, the quality of the studies was evaluated using the Cochrane risk of bias tool, as shown in Fig 2.


Acute-on-chronic liver failure (ACLF) is a severe and potentially fatal condition that occurs in patients with pre-existing chronic liver disease. It is characterized by acute decompensation and organ failure, which significantly increases morbidity and mortality rates. The treatment of ACLF remains a major challenge, and current therapeutic options are limited. In recent years, granulocyte colony-stimulating factor (G-CSF) has been proposed as a potential therapy for ACLF. G-CSF is a cytokine that stimulates the production and differentiation of neutrophils and has been shown to have immunomodulatory and anti-inflammatory effects [25]. In this meta-analysis, we evaluated the efficacy and safety of G-CSF therapy in the treatment of ACLF.

Citation: Qiu B, Liang JX, Romero Gómez M (2023) The efficacy and safety of granulocyte colony-stimulating factor in the treatment of acute-on-chronic liver failure: A systematic review and meta-analysis. PLoS ONE 18(11): e0294818.

Editor: Sona Frankova, Institute for Clinical and Experimental Medicine, CZECH REPUBLIC

Received: May 22, 2023; Accepted: November 9, 2023; Published: November 30, 2023

Copyright: © 2023 Qiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: G-CSF, granulocyte-colony stimulating factor; ACLF, acute-on-chronic liver failure; BMSCs, bone marrow stem cells; MELD, Model for end stage of liver disease; CTP-scores, Child–Turcotte–Pugh scores; INR, international normalized ratio; HE, hepatic encephalopathy; RCT, randomized clinical trials; RR, risk ratios; Cl, confidence intervals; MD, mean differences; SD, standard deviation

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