Therapeutic Effect and Safety of Granulocyte Colony-Stimulating Factor Therapy for Acute-On-Chronic Liver Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background and Aims: Granulocyte colony-stimulating factor (G-CSF) has been proposed as a therapeutic option for patients with acute-on-chronic liver failure (ACLF). However, its clinical efficacy remains debatable. This study aimed to synthesize available evidence on the efficacy of G-CSF in ALCF.Methods: The Cochrane Library, CNKI, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched from inception until September 2021. After qualitative evaluation of the included literature, the included studies were analyzed.Results: Seven studies were included in this meta-analysis. Overall, G-CSF therapy was not associated with a reduced risk of death (30-day survival, OR = 1.55, 95% CI: 1.00, 2.38, P = 0.05; 60-day survival, OR = 1.50, 95% CI: 0.95, 2.36, P = 0.08; 90-day survival, OR = 1.61, 95% CI: 0.99, 2.62, P = 0.05) or complication including occurrence of infections infection (OR = 0.66, 95% CI: 0.41, 1.05, P = 0.08), bleeding (OR = 1.50, 95% CI: 0.58, 3.89, P = 0.41), and hepatorenal syndrome (OR = 0.56, 95% CI: 0.25, 1.24, P = 0.15). Moreover, it had no obvious beneficial effects on the model of end-stage liver disease score (30-day SMD = −3.31, 95%CI: −7.42, 0.81, P = 0.12; 60-day SMD = −1.23, 95% CI: −5.21, 2.75, P = 0.54; 90-day SMD = −2.29, 95%CI: −4.94, 0.37, P = 0.09). Sensitivity analyses showed that patients in Asia had improved survival (30-day OR = 2.76, 95%CI: 1.43, 5.35, P = 0.003; 60-day OR = 2.83, 95% CI: 1.39, 5.73, P = 0.004; 90-day OR = 2.92, 95% CI: 1.34, 6.36, P = 0.007).Conclusions: Our findings suggest that, currently, G-CSF cannot be recommended for the treatment of ACLF.

Granulocyte-colony stimulating factor in decompensated liver cirrhosis: a meta-analysis of four randomized controlled trials

“…MELD is an indicator of liver disease severity and estimates the 3 months of survival in patients with end-stage liver disease. It uses the following indices: bilirubin, creatinine, INR, sodium, and whether dialysis is initiated [ 13 ]. Our meta-analysis shows a small but non-significant decrease in the MELD score.…”

Review article: Emerging and current management of acute‐on‐chronic liver failure

“…G‐CSF pre‐treatment has also been found to aggravate lipopolysaccharide‐induced portal hypertension and microcirculatory disorders, which suggests that G‐CSF may induce lipopolysaccharide‐sensitisation 95 . As such, the beneficial effects of G‐CSF in ACLF may be limited by the fact that G‐GCF requires a non‐inflammatory environment to exert its protective effects on the liver 96 …”

“…95 As such, the beneficial effects of G-CSF in ACLF may be limited by the fact that G-GCF requires a non-inflammatory environment to exert its protective effects on the liver. 96 Increased levels of serum G-CSF have been reported in patients with systemic inflammatory response syndrome (SIRS) compared to those without SIRS 9 and it is possible that G-CSF, in the setting of systemic inflammation, is contributing to 'emergency haematopoiesis'. Therefore, additional G-CSF in the setting of pre-existing inflammation may accelerate the cytokine storm.…”

Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

“…It is often caused by acute liver injury or the progressive development of liver fibrosis or other chronic liver disease such as virus infection, etc. In China, the total number of patients with various types of chronic liver disease exceeds 300 million, and more than 1 million people die each year from ESLD [6]. According to the Centers for Disease Control (CDC), ESLD is the twelfth leading cause of death in the United States, with approximately 44,000 deaths per year [7].…”