Serum CXCL1 Is a Prognostic Factor for Patients With Hepatitis B Virus–Related Acute-On-Chronic Liver Failure

Abstract

Purpose: Neutrophils and cytokines play a major role in the pathogenesis of acute-on-chronic liver failure (ACLF). We aimed to determine whether chemokine (CXC) ligand 1 (CXCL1), a key marker of neutrophil recruitment and activation, could predict the severity and prognosis of hepatitis B virus–related ACLF (HBV-ACLF).Methods: Hospitalized patients with HBV-ACLF were enrolled in a prospective study and stratified as survivors (alive at 28 days) and nonsurvivors (deceased at 28 days). Serum CXCL1 levels were measured in healthy controls, patients with chronic HBV, patients with HBV-related compensated cirrhosis, and patients with HBV-ACLF. Univariate and multivariable logistic analyses, Pearson correlation analysis, area under the receiver operating characteristic curve (AUROC), and Z tests were used to evaluate the performance of CXCL1 as a marker in HBV-ACLF.Results: Patients with HBV-ACLF had significantly higher serum levels of CXCL1 and neutrophil count than healthy controls and patients with chronic HBV or HBV-related compensated cirrhosis (P < 0.01, respectively). Among patients with HBV-ACLF, survivors had lower serum CXCL1 levels and neutrophil count than those of nonsurvivors (P < 0.001, P < 0.05, respectively). Serum CXCL1 level was positively correlated with neutrophil count (r = 0.256, P = 0.001), ACLF grade (r = 0.295, P < 0.001) and organ failure, including coagulation (r = 0.21, P = 0.005) and brain failure (r = 0.198, P = 0.008). Multivariable logistic analyses showed serum CXCL1 [OR (95% CI) = 1.017 (1.009–1.025), P < 0.001] was an independent risk factor for 28-day mortality in HBV-ACLF. Meanwhile, the AUROC analysis demonstrated that serum CXCL1 [0.741 (0.669–0.804)] might be a reliable prognostic biomarker for patients with HBV-ACLF.Conclusions: Overall, serum CXCL1 can serve as a biomarker indicating the severity of disease and prognosis for patients with HBV-ACLF. CXCL1 might also be a therapeutic target in this disease.

Per‐ and polyfluoroalkyl substances activate UPR pathway, induce steatosis and fibrosis in liver cells

“… 82 On the other hand, IL24 protects against liver fibrosis 83 and IL1β has been proposed as an important mediator of inflammation and tissue damage in chronic liver disease. 84 TIMP3 expression prevents diet‐dependent fatty liver disease and hepatocellular carcinoma, 85 while expression of CXCL1 in serum can serve as a prognostic biomarker for patients with HBV‐ACLF 86 and PTX3 can serve as an inflammatory biomarker for the prognosis of patients with hepatic cirrhosis. 87 Our Gene ontology analysis revealed that chronic PFOA exposure affects several pathways including TNF, PI3K/AKT, Foxo, p53, insulin signaling, and insulin resistance pathways.…”

ETS2 alleviates acute‐on‐chronic liver failure by suppressing excessive inflammation

“…5 Neutrophil dysfunction has been reported to produce hepatocellular dysfunction in sepsis, and serum CXCL1 is a neutrophil marker, which is also indicative of poor prognosis in ACLF. 25,26 This study highlights the therapeutic effect of ETS2 on the excessive inflammatory response in ACLF. Previous studies have suggested that the benefit from anti-inflammatory therapy is conditional due to the complex pathophysiological background of ACLF.…”

“…ETS2 is expressed in a variety of cell types (endothelial cells, macrophages, and stromal fibroblasts) and has been implicated in various diseases, such as atherosclerosis, diabetes mellitus, and the cecal ligation and Although there are many biomarkers for the prognosis of ACLF, the discovery of these molecules has mostly been based on clinical laboratory indicators, which do not reflect the complex backgrounds of diseases. [22][23][24][25] However, the current study was based on a multigroup comparison using transcriptomics, which is more rigorous in terms of methods. Compared to histological biopsy, the use of ETS2 as a noninvasive single biomarker to distinguish the prognosis of ACLF patients is simple and practical.…”

“…Although there are many biomarkers for the prognosis of ACLF, the discovery of these molecules has mostly been based on clinical laboratory indicators, which do not reflect the complex backgrounds of diseases 22–25 . However, the current study was based on a multigroup comparison using transcriptomics, which is more rigorous in terms of methods.…”

“…The increase in WBC count is associated with a progressively increased mortality rate and is independent of bacterial infection 5 . Neutrophil dysfunction has been reported to produce hepatocellular dysfunction in sepsis, and serum CXCL1 is a neutrophil marker, which is also indicative of poor prognosis in ACLF 25,26 …”