程序性死亡受体-1在不同基线乙型肝炎病毒DNA患者阿德福韦酯治疗后的变化  

Changes of programmed death receptor-1 in patients with different baseline hepatitis B virus DNA levels after treatment with adefovir dipivoxil

作　　者：周玉麟[1] 王学才[1] 顾锡炳[2] 朱银芳[2] 杨小娟[2] 王娟华[2] 华忠[2] 

机构地区：[1]江苏省宜兴市人民医院传染科,214200 [2]无锡市第五人民医院无锡市传染病医院肝病科

出　　处：《中华传染病杂志》2014年第10期589-593,共5页Chinese Journal of Infectious Diseases

摘　　要：目的 探讨不同基线HBV DNA水平CHB患者阿德福韦酯（ADV）治疗后程序性死亡受体-1（PD-1）的变化.方法 100例1×10 4拷贝/mL≤HBV DNA≤1×10 7拷贝/mL、HBeAg阳性、人白细胞抗原（HLA）-A2阳性的CHB患者,根据基线HBV DNA水平分为两组：低病毒载量组47例,HBV DNA≤1×105拷贝/mL;高病毒载量组53例,HBV DNA＞1×10 5拷贝/mL.均用ADV 10 mg/d治疗,比较两组患者治疗前和治疗12个月后的血清HBV DNA、HBeAg血清学转换率、ALT和TBil.流式细胞技术检测外周血HBV特异性CTL表面PD-1、外周血HBV特异性CTL水平.计数资料比较用x2检验,两样本均数比较用t检验.结果 基线低病毒载量组CHB患者外周血HBV特异性CTL表面PD-1为20.17％±1.69％,低于高病毒载量组的41.38％±2.30％ （t=53.02,P＜0.01）;外周血HBV特异性CTL水平分别为0.37％±0.02％和0.17％±0.02％ （t=50.47,P＜0.01）;低病毒载量组ALT和TBil水平均低于高病毒载量组（t值分别为=13.07和5.06,均P＜0.01）.治疗12个月后,低病毒载量组与高病毒载量组比较,HBV DNA阴转（HBV DNA＜500拷贝/mL）分别有25例（53.2％）和10例（18.9％,x2=12.89,P＜0.01）,发生HBeAg血清学转换分别为15例（31.9％）和1例（1.9％）（x2 =16.72,P＜0.01）,外周血HBV特异性CTL表面PD-1表达水平分别为9.00％±1.38％和29.40％±3.76％（t=36.80,P＜0.01）,外周血HBV特异性CTL水平分别为0.65％±0.10％和0.48％±0.07％（t=9.61,P＜0.01）.结论 ADV治疗CHB患者后,随着HBV DNA载量下降,HBV特异性CTL表面PD-1的表达水平下降,HBV特异性CTL水平升高;低病毒载量组的变化更明显.Objective To explore the changes of programmed death receptor-1 （PD-1） in chronic hepatitis B （CHB） patients with different baseline of hepatitis B virus （HBV） DNA levels after treatment with adefovir dipivoxil （ADV）.Methods One hundred CHB patients with positive hepatitis B e antigen （HBeAg）,1 × 104 copy/mL≤HBV DNA≤1 × 107 copy/mL,and positive human leukocyte antigen-A2 were divided into two groups according to the baseline HBV DNA level：47 cases in low virus load group whose HBV DNA level was ≤1 × 105 copy/mL; 53 cases in high virus load group whose HBV DNA level was〉1 × 105 copy/mL.Both groups were treated with ADV 10 mg/d.Serum HBV DNA,HBeAg seroconversion rate,alanine aminotransferase （ALT） and total bilirubin （TBil） levels of both groups before treatment and 12 months after treatment were compared.Flow cytometry was used to test peripheral blood HBV-specific cytotoxic T lymphocyte （CTL） surface PD-1 and peripheral blood HBV-specific CTL level.Categorical data were tested by x2 test; quantitative data was compared with t-test.Results Peripheral blood HBV-specific CTL surface PD-1 of CHB patients in low virus load group was 20.17 %±1.69%,which was lower than that in high virus load group （41.38%±2.30%,t =53.02,P〈0.01） ; peripheral blood HBV specific CTL levels in two groups were 0.37%±0.02% and 0.17%± 0.02%,respectively （t=50.47,P〈0.01） ; ALT and TBil levels in low virus load group were both lower than those of high virus load group （t=13.07,P〈0.01; t=5.06,P〈0.01）.Twelve months after treatment,HBV DNA of 25 cases （53.2%） in low virus load group and 10 cases （18.9%） in high virus load group were lower than the detectable level （HBV DNA〈500 copy/mL,x2 =12.89,P〈0.01）;HBeAg seroconversion was achieved in 15 cases（31.9%） and 1 case （1.9%）,respectively （x2 =16.72,P〈0.01） ; peripheral blood HBV-specific CTL surface PD-1 expression levels were 9.00 % ±1.38 % and 29.40 % ± 3.76 %,respectively （t =36.80,P〈 0.01）

关 键 词：肝炎 乙型 慢性 肝炎病毒 乙型 DNA病毒 程序性死亡受体-1 T淋巴细胞 细胞毒性 阿德福韦酯 

分 类 号：R512.62[医药卫生—内科学]