调节性T细胞及病毒分型对拉米夫定治疗HBV感染患者耐药发生的影响

Influences of regulatory T cells and viral typing on drug resistance of HBV infection patients with lamivudine therapy

目的 :探讨CD4+CD25+、CD8+CD28-Treg细胞水平和基线因素对拉米夫定治疗HBV感染患者4周病毒学应答及2年耐药发生率的影响。方法:入选我院门诊、住院慢性HBV感染患者84例,入组患者均给予拉米夫定100 mg/d。治疗前检测生化、HBVDNA载量、乙肝病毒基因分型及T细胞亚群、CD4+CD25+、CD8+CD28-百分比。治疗4周根据HBVDNA是否能检测出,分为4周应答组和非应答组;治疗96周根据患者是否发生拉米夫定耐药分为未耐药组和耐药组。以上四组分别两两比较基线指标和T细胞亚群、CD4+CD25+、CD8+CD28-水平。结果:应答组和非耐药组的HBVDNA载量、HBe Ag阳性率均低于非应答组和耐药组,差异有统计学意义(P<0.05)。HBV基因构成比和ALT水平各组比较无统计学差异(P>0.05)。4周应答组和非耐药组的CD4+CD25+水平高于非应答组和耐药组(P<0.05);耐药组CD8+CD28-水平高于非耐药组,差异有统计学意义(P<0.05)。CD3+、CD4+、CD8+百分比在以上各两组比较中无统计学差异(P>0.05)。结论:CD4+CD25+、CD8+CD28-水平、e抗原状态和HBVDNA载量对拉米夫定治疗患者的4周病毒学应答和2年耐药发生率有一定影响,乙肝病毒基因分型与病毒学应答和耐药无关。

Objective： To explore the influences of viral response and resistance with lamivudine therapy on CD4＋ CD25＋, CD8＋CD28- regulatory T cell levels and hepatitis B virus genotype. Methods： 84 patients with chronic hepatitis B-related in our outpatient or inpatient were enrolled who were initially treated with lamivudine,100 mg/day. Before the therapy, biochemical test, HBVDNA load,serum mark, hepatitis B virus genotype, T cell subsets, CD4＋CD25＋and CD8＋CD28- levels were detected. According to HBVDNA level after 4-week therapy, patients were divided into two groups,4-week response group and non response group.Followed to 96 weeks, according to whether patients occurred to lamivudine resistance ,were divided into no resistance group and resistance group. Results： HBVDNA loads and the positive rates of HBeAg in viral response group and non resistance group were significantly lower than that in non response group and resistant group（P＆lt;0.05）. There were no significant difference in HBV genotype and ALT levels in four groups（P＆gt;0.05）. levels of CD4＋CD25＋in viral response group and non resistance group were significantly higher than in non response group and resistance group（P＆lt;0.05） while levels of CD8＋CD28- in resistance group was higher than in non resistance group （P＆lt;0.05）.There were no significant difference in CD3＋, CD4＋and CD8＋among four groups（P＆gt;0.05）. Conclusion：Levels of CD4＋CD25＋, levels of CD8＋CD28-, e-antigen and HBVDNA level affects viral response and resistance of Hepatitis B-related patients with lamivudine therapy in which it seems that there is no relationship between viral genotype and viral response or resistance.