聚乙二醇干扰素α-2a联合恩替卡韦治疗慢性乙型肝炎患者疗效及其外周血单个核细胞TLR4和B7-H1表达变化  

Antiviral response and changes of TLR4 and B7-H1 in peripheral blood mononuclear cells by peginterferonα-2a and entecavir combination therapy in patients with chronic hepatitis B

作　　者：徐欢 谭钧元 黄荷 董丹丹 Xu Huan;Tan Junyuan;Huang He(Department of Infectious Diseases,Seventh Hospital,Wuhan 430071,Hubei Province,China)

机构地区：[1]武汉市第七医院感染病科,430071 [2]解放军总医院第五医学中心医务部 [3]华中科技大学同济医学院附属武汉中心医院消化内科

出　　处：《实用肝脏病杂志》2022年第5期637-640,共4页Journal of Practical Hepatology

基　　金：武汉市卫健委医学科研项目(编号:S201802260046)。

摘　　要：目的探讨应用聚乙二醇干扰素α-2a(peg-IFNα-2a)联合恩替卡韦治疗慢性乙型肝炎(CHB)患者的疗效及外周血单个核细胞(PBMCs)Toll样受体4(TLR4)和协同刺激分子B7家族1(B7-H1)表达变化。方法2019年7月~2021年7月我院诊治的CHB患者96例,被随机分为对照组48例和观察组48例,分别接受恩替卡韦或恩替卡韦联合Peg-IFNα-2a治疗48周。采用ELISA法检测血清Ⅳ型胶原、层粘连蛋白、Ⅲ型前胶原、透明质酸、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)和IL-6;使用流式细胞仪检测PBMCs表面TLR4和B7-H1表达水平。结果在治疗结束时,观察组血清HBeAg转阴率为37.5%,显著高于对照组的14.6%(P<0.05),血清HBeAg血清转换率为25.0%,显著高于对照组的0.0%(P<0.05);两组血清AST和ALT水平均恢复正常,差异无统计学意义(P>0.05);观察组血清Ⅳ-C水平为(83.9±17.7)μg/L,血清LN水平为(89.2±25.5)μg/L,血清HA水平为(124.9±22.7)μg/L,均显著低于对照组【分别为(106.5±20.3)μg/L、(124.1±32.7)μg/L和(179.2±38.4)μg/L,P<0.05】;观察组血清IL-10水平为(30.6±5.7)pg/mL,显著高于对照组【(20.4±8.6)pg/mL,P<0.05】,而血清TNF-α水平为(28.8±7.4)mg/L,显著低于对照组【(39.1±9.7)mg/L,P<0.05】,血清IL-6水平为(19.1±3.8)pg/mL,显著低于对照组【(27.5±5.4)pg/mL,P<0.05】;观察组PBMCs表面TLR4表达水平为(10.2±3.1)%,显著低于对照组【(15.8±4.6)%,P<0.05】,PBMCs表面B7-H1表达水平为(8.9±1.5)%,显著低于对照组【(11.6±2.2)%,P<0.05】。结论联合应用Peg-IFNα-2a和恩替卡韦治疗CHB患者具有良好的疗效,能抑制HBV复制,缓解肝纤维化进程,改善肝功能和机体炎症反应,降低PBMCs表面TLR4和B7-H1表达,值得进一步研究。Objective The aim of this study was to investigate the antiviral response and changes of Toll-like receptor 4(TLR4)and costimulatory molecule B7-H1(B7-H1)in peripheral blood mononuclear cells(PBMCs)by peginterferonα-2a(peg-IFNα-2a)and entecavir combination therapy in patients with chronic hepatitis B(CHB).Methods A total of 96 patients with CHB were enrolled in our hospital between July 2019 and July 2021,and were divided into control group(n=48)and observation group(n=48),receiving entecavir or entecavir and peg-IFNα-2a combination treatment for 48 weeks.Serum collagen type IV(IV-C),laminin(LN),procollagen type III(PG III)and hyaluronic acid(HA)levels,and serum interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and IL-6 levels were detected by ELISA.The percentages of TLR4 and B7-H1 on the surface of PBMCs were detected by flow cytometry.Results At the end 48 weeks of treatment,the negative conversion rate of serum HBeAg in the observation group was 37.5%,significantly higher than 14.6%(P<0.05),and HBeAg seroconversion rate was 25.0%,significantly higher than 0.0%(P<0.05)in the control group;serum ALT and AST levels in the two groups were back to normal and there was no significant differences between them(P>0.05);serumⅣ-C level in the observation was(83.9±17.7)μg/L,serum LN level was(89.2±25.5)μg/L and serum HA level was(124.9±22.7)μg/L,all significantly lower than[(106.5±20.3)μg/L,(124.1±32.7)μg/L and(179.2±38.4)μg/L,respectively,P<0.05]in the control;serum IL-10 level in the observation was(30.6±5.7)pg/mL,significantly higher than[(20.4±8.6)pg/mL,P<0.05],while serum TNF-αlevel was(28.8±7.4)mg/L,significantly lower than[(39.1±9.7)mg/L,P<0.05],and serum IL-6 level was(19.1±3.8)pg/mL,significantly lower than[(27.5±5.4)pg/mL,P<0.05]in the control;the percentage of TLR4 expression in the surfaces of PBMCs was(10.2±3.1)%,significantly lower than[(15.8±4.6)%,P<0.05]and the percentage of B7-H1 expression was(8.9±1.5)%,significantly lower than[(11.6±2.2)%,P<0.05]in the control group.Conc

关 键 词：慢性乙型肝炎 聚乙二醇干扰素Α-2A Toll样受体4 协同刺激分子B7家族1 治疗 

分 类 号：R512.62[医药卫生—内科学]