Methylation Of Interleukin-8 Promoter Predicts The Response To Nucleos(t)ide Analogs Therapy In Chronic Hepatitis B

Background and aims:This study aimed to determine the methylation status of the IL-8 promoter in patients with chronic hepatitis B(CHB)and analyze its prognostic value in nucleos(t)ide analogs(NAs)antiviral therapy at 24th week.Methods:A total of 174 subjects were included in this retrospective cohort,which contained 126 patients with CHB and 48 health controls(HCs).Patients with CHB who matched the selection criteria were divided into two subgroups according to kinds of NAs.IL-8 promoter methylation status was determined by methylation-specific polymerase chain reaction(MSP).Results:1.The methylation rate of IL-8 gene promoter in PBMCs of CHB patients was significantly lower than that of HCs group.(36.508%VS 66.667%,P<0.001)2.There was no correlation between the methylation status of IL-8 in CHB patients and gender(P = 0.082),age(P=0.057),Hepatitis B virus e antigen(HBeAg)(P = 0.896),log10[HBV DNA](P=0.944),Alanine aminotransferase(ALT)(P=0.108),Aspertate aminotransferase(AST)(P=0.122),glutamyl transpeptidase(GGT)(P=0.400),Alkaline phosphatase(AKP)(P=0.430),Total bilirubin(TBIL)(P=0.176)and Albumin(Alb)(P=0.935).3.There was a significant increase in IL-8 promoter methylation frequency in serological responders(P=0.001)and complete virological responders than nonresponders.The similar results were found in entecavir subgroup.4.IL-8 gene promoter methylation status(P=0.024)and log10[HBV DNA]level(P=0.022)are independent risk factors in predicting the complete virological response of patients with CHB with taking entecavir for 24 weeks.5.The value of IL-8 gene promoter methylation in predicting the complete virological response for CHB patients with entecavir antiviral treatment:the area under the receiver-operating curve(AUC)is 0.740.The AUC of log10[HBV DNA]is 0.652.Combination of the two factors,the AUC is 0.754 and the sensitivity and specificity is 83.3%and 68%,respectively.Conclusions:Hypomethylation status of IL-8 promoter was found in patients with CHB.IL-8 promoter methylation status might be a independent factor in predicting the complete virological response at the 24th week in CHB patients with entecavir therapy.