HBV疫苗诱导树突状细胞和T淋巴细胞表达对聚乙二醇干扰素治疗慢性乙肝患者病毒学应答的影响

Expression of dendritic cells and cytotoxic T lymphocyte induced by hepatitis B vaccination and its impact onvirological response in patients with chronic hepatitis B treated with pegylated interferon

目的探讨乙肝疫苗诱导树突状细胞(DC)和特异性细胞毒性T淋巴细胞(CTL)表达促进聚乙二醇干扰素α(peg-IFN-α)治疗慢性乙型病毒性肝炎(CHB)患者病毒学应答的效果及安全性。方法2016年1月-2019年1月南京军区福州总医院肝胆内科和福建医科大学孟超肝胆医院收治的120例HBeAg阳性CHB初治患者,随机分为疫苗诱导+pegIFN-α治疗组(治疗组)和peg-IFN-α单药治疗组(对照组),各60例。治疗组采取HBV疫苗皮下多点注射,20μg/次,1次/4周,共3次;诱导开始2周后注射peg-IFN-α180μg/次,1次/7 d,总疗程50周。对照组皮下注射peg-IFN-α180μg/次,1次/7 d,总疗程48周。检测两组患者治疗治疗前后12周的免疫学指标(DCs计数、IL-12水平和HBV特异性CTL细胞IFN-γ反应率和反应强度);24和48周时HBV DNA阴转率、HBeAg血清学转换率及HBsAg转阴率。结果最终108例完成实验(治疗组55例,对照组53例),两组患者抗病毒治疗前DCs数量和IL-12分泌水平均处于较低的水平,抗病毒治疗12周后DCs数量和IL-12水平较疗前均有明显上升,差异有统计意义(P<0.001)。治疗组与对照组相比DCs计数、IL-12水平和特异性CTL细胞IFN-γ反应强度,差异具有统计学意义(P<0.001)。治疗24周、48周的HBV DNA转阴率、HBeAg血清转换率,两组比较差异无统计学意义;但治疗组48周HBsAg转阴率,治疗组明显高于对照组两组比较差异有统计学意义(P<0.05)。结论多点注射乙肝疫苗能够诱导CHB患者树突状细胞和HBV特异性CTL细胞表达及其细胞因子的分泌,提高聚乙二醇干扰素α治疗CHB患者的HBsAg转阴率。

Objective To investigate the effect of hepatitis B vaccination on dendritic cells(DC)and cytotoxic T lymphocyte(CTL)expressions and virological response in patients with chronic hepatitis B being treated with pegylated interferon.Methods A total of 120 patients with HBeAg positive treatment-naive chronic hepatitis B(CHB)who visited the outpatient service or were hospitalized in Fuzhou General Hospital and Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2016 to January 2019 were divided randomly intotreatment group(60 cases)and control group(60 cases).The patients in the two groups were treated with pegylated interferon alpha(180μg,subcutaneous injection,once a week)for 48 weeks,on this basis,the patients in the induction group were treated with hepatitis B vaccination(20μg,multiple subcutaneous injection,once four weeks)for 3 times before interferon treatment for 2 weeks.The levels of dendritic cells andIL-12,and the magnitudes of IFN-γreleasing induced by HBVspecific cytotoxic T lymphocyte were measured before and 12 weeks after treatment.The negative rate of HBV-DNA,HBsAg,serological conversion rate of HBeAg of the patients in the two groups were observed after 24 and 48 weeks.Results Finally 108 cases(55 in the treatmentgroup and 53 in the control group)completed the course of treatment,and involved in the analysis of results.After 12 weeks of treatment,the IL-12 levels of serum and DCs amounts in both groups were significantly higher than those before treatment(P<0.001).The DCs amounts,IL-12 levels of serum and the magnitudes of IFN-γreleasing induced by HBVspecific CTL were significantly different between two group(P<0.001).There were no significant differences of HBV-DNA negative rates and HBeAg seroconversion rates between the two groups after 24 and 48 weeks treatment.The negative rate of HBsAg was significantly higher in the treatment group than that in the control group after 48 weeks treatment(P<0.05).Conclusion It is found that hepatitis B vaccination could induce DC and CTL proliferation,promote cytokines secreting,and improve HBV-DNA negative rate in patients with chronic hepatitis B being treated with pegylated interferon.