The Changes Of IL-23/IL-17 Signaling Pathway Activity In Patients With Chronic Hepatitis B And The Effect Of Antiviral Therapy To It

Objective:By analyzing the effect of before and after antiviral treatment to the changes of peripheral Th17 cells,the expression of RORyt mRNA,and the related cytokines of IL-23 and IL-17,in combination with the correlation with liver function index such as ALT,AST,TBIL,the status of HBeAg and the level of HBV replication,to investigate the activity of IL-23/IL-17 signaling pathway in patients with chronic hepatitis B,and the effect of antiviral therapy on IL-23/IL-17 signaling pathway in patients with chronic hepatitis B,so that provide a new theoretical basis for the pathogenesis and clinical treatment of chronic hepatitis B.Methods:One hundred and eleven patients with HBeAg positive chronic hepatitis B were involved in this study,who came from inpatient or outpatient in department of infectious diseases of the First Affiliated Hosipital of Kunming Medical University from October 2014 to October 2016.Among them,sixty eight patients were male,forty three patients were female.All patients were given Entecavir(ETV)0.5mg/d antiviral therapy for 48 weeks.Twenty two were normal physical examination people in our hospital as health control(HC).Among them,fourteen were male,eight were female.The frequency of Th17 cells in the peripheral blood of the patients group and control group were detected by flow cytometry;Real-time fluorescent quantitative reverse transcriptase polymerase chain reaction(RT-PCR)was used to measure the level of RORyt mRNA in the peripheral blood;Enzyme linked immuo-adsordent assay was used to check levels of IL-23,IL-17;The HBV-markers of HBeAg was determined by ELISA;The HBV DNA were tested by real-time fluorescent quantitative PCR analyzer;The ALT,AST,TBil and other liver function indicators were detected by the automatic biochemical analyzer.All of these data were analyzed by the SPSS 22.0 statistical software.Results:1.In one hundred and eleven cases were 61.3%(68/111)of male,were 38.7%(43/111)of female.The average age was 34.5 ± 8.6,the average HBV DNA was 5.37*107(20.42)cp/ml,the level of HBV DNA with all patients were more than 105 cp/ml.There were 82%(92/111)patients' HBV DNA levels were more than 107 cp/ml.There was a significant difference in gender distribution,age,ALT,AST and TBIL levels in chronic hepatitis B group and control group(all P less than 0.05).The mean age,ALT,AST and TBIL levels in the chronic hepatitis B group were significantly higher than those in the control group.The frequency of Th17 cells in chronic hepatitis B group[3.18(5.85)vs 2.68(1.93)],RORyt count[2.78(2.36)vs 1.98 ± 0.80],IL-17[423.0(88.2)vs 159.5(45.8)]and IL-23[359.9(67.9)vs 151.6(31.7)]were higher than those in control group,and the difference were statistically significant(all P less than 0.05).2.There were no correlation between liver function(ALT,AST,TBIL)and immune related indexs(Th17,RORyt,IL-17,IL-23)before and a:fter treatment in patients with chronic hepatitis B(all P more than 0.05).There was no correlation between Th17 and RORyt with HBV DNA(all P more than 0.05)before and after treatment,but was significantly positively correlated with IL-23 and IL-17(r = 0.565,0.385,0?560,0.572;all P less than 0.05).After treatment,HBeAg was negatively correlated with Th17,ROR?t,IL-23 and IL-17,and the difference were statistically significant(r?-0.485?-0.330?-0.445?-0.505;all P less than 0.05).3.In patients with chronic hepatitis B,with the prolongation of treatment time,the ALT recurrence rate,HBV DNA undetectable rate and HBeAg seroconversion rate increased gradually.After 48 weeks of treatment,the ALT recurrence rate,HBV DNA undetectable rate and HBeAg seroconversion rate were 94.6%,80.2%and 18.0%respectively.4.Compared with before treatment,treatment for 48 weeks with CHB patients,the levels of Th17(3.03 ± 1.73 vs 5.35 ± 3.40),RORyt(1.94 ± 1.04 vs 3.32 ± 1.36),IL-17[268.6 ± 62.9 vs 423.0(88.2)]and IL-23[256.8 ± 65.5 vs 359.9(67.9)]were significantly decreased(all P less than 0.05).5.Patients with chronic hepatitis B antiviral treatment for 48 weeks,according to the level of HBV DNA,divided into HBV DNA detectable group and HBV DNA undetectable group,compared two groups' levels of Th17,RORyt,IL-17 and IL-23 before and after treatment respectively,there were no significant differences(all P more than 0.05),but the trend of downside was same,and before 12 weeks HBV DNA load decreased the fastest.According to the level of HBeAg,divided into HBeAg positive group and HBeAg negative group and HBeAg/HBeAb seroconversion group,compared three groups of levels of Th17,ROR?t,IL-17 and IL-23 before and after treatment respectively,only Th17 showed no significant difference between the three groups after treatment(all P more than 0.05),all the others were statistically significant(all P less than 0.05).And HBeAg/HBeAb seroconversion group,the levels of Th 17,RORyt,IL-17 and IL-23 were lower than the HBeAg positive group(all P less than 0.05).Conclusion:IL-23/IL-17 signal pathway associated with HBV infection,with its specific mechanism may be related with inflammation which induced and not kill hepatocyte directly.Entecavir in the improvement of ALT and HBV DNA was superior to HBeAg seroconversion,and the main reason was that could not regulate the immune system directly.Therefore,the further study of IL-23/IL-17 signaling pathway activity in patients with chronic hepatitis B,may be provide a new theoretical basis for the pathogenesis and clinical treatment of chronic hepatitis B.