Clinical Significance Of Serum Levels Of IL-8 In Patients With HBV-acute-on-chronic Liver Failure

Objective: To investigate the clinical significance of serum levels of IL-8 in patients with HBV-ACLF.Methods: The level of interlukin-8(IL-8)in liver tissue were analysed by immunohistochemistry in Totally 62 HBV-ACLF patients and 57 patients with chronic hepatitis B(CHB).ELISA was used to detect the serum level of IL-8.Meanwhile,HBV DNA and several liver function indexes such as alanine aminotransferase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),total bilirubin(TBIL)and creatinine(Cr)were examined as well.According to the clinical outcomes of patients,HBV-ACLF group was divided into improved group and death group,and calculate MELD scores.PBMCs were isolated from peripheral blood with Ficoll solution and then divided into four groups,namely control group,IL-8 group,IFN-α group and combined treatment group.To investigate moleculars of JAK-STAT signal transduction pathway and the antiviral protein(STAT1、STAT2、IRF9、Mx A)expressions through RT-q PCR and Western blot method.Results: IL-8 levels in serum and liver tissues of HBV-ACLF patients were both significantly higher than those in CHB group and healthy control group(P<0.05).Through the Pearson Correlation Analysis,serum IL-8 quantification was positively correlated with HBV-DNA load when HBV>500 IU/ml(r=0.416,P<0.05).Compared with CHB patients and healthy controls,liver function indicators such as ALT,AST,ALP,TBIL and Cr were obviously increased in HBV-ACLF patients.Besides,serum IL-8 quantification was positively correlated with ALT and AST(r=0.247,P<0.05;r=0.317,P<0.05).According to the clinical outcomes of patients,HBV-ACLF group was divided into improved group and death group,and serum IL-8 levels in death group was significantly higher than improved group(P<0.05).And serum IL-8 quantification was positively correlated with MELD score(r=0.247,P<0.05).Compared the expression of STAT1,STAT2,IRF9 and other related signal transduction molecules and anti viral protein Mx A in four groups of HBV-ACLF patients’ PBMCs,it was found that the expression level of IFN-α group was highest(P<0.05),while combined treatment group was the lowest(P<0.05),which suggested that IL-8 may influence JAK-STAT signal transduction pathways through some mechanism,and inhibit the expression of viral proteins.And compared to IFN-α group,the expression of signal transduction molecules and anti viral protein in combined treatment group was significantly decreased(P<0.05).It showed that IL-8 may decrease the expression of antiviral protein to antagonize the antiviral activity of IFN-α,suggesting that it may execute negative effects to the antivirus activity of IFN-ɑ.Conclusion: IL-8 level in serum and liver tissue of HBV-ACLF patients increased significantly,and the serum IL-8 level was related to the degree of liver inflammation injury and the severity of HBV-ACLF.IL-8 may inhibit the expression of JAK-STAT pathway molecules and antiviral protein Mx A in PBMCs of HBV-ACLF patients,and may have a negative effect on the antiviral effect of IFN-α.