HLA-DR与慢性乙肝持续病毒应答的相关性研究

Study on the correlation between HLA-DR and HBV sustained virological response

目的通过分析人类白细胞抗原-DR(HLA-DR)抗原与抗HBV疗效的相关性,探讨影响拉米夫定治疗慢性乙肝的自身因素。方法观察和比较HBeAg阳性和阴性慢性乙肝各160份全血标本及临床治疗资料,采用PCR-SSP方法检测患者HLA-DR抗原基因位点信息,分析HLA-DR检测的位点信息与拉米夫定服药患者持续病毒应答的相关性。结果 HBeAg阳性的乙肝患者的持续病毒应答能力较差,即在持续服用拉米夫定治疗后均有肝功和病毒复制数的反复;HLA-DR基因分布在服用拉米夫定后的HBeAg阳性和阴性患者中存在差异:HBeAg阳性患者中DR3、7、8、14的基因频率(GF:0.217;0.141;0.045;0.22)明显高于HBeAg阴性患者(GF:0.006;0.038;0.006;0.055)(P<0.01),而HLA-DR4、13的基因频率(GF:0.035;0.029)明显低于HBeAg阴性患者(GF:0.193;0.225)(P<0.01)。结论 HLA-DR3、7可能具有促进HBV持续感染降低拉米夫定疗效作用,而HLA-DR4、13则作用相反,而HLA-DR8、14与抗HBV的相关性有待证明,此研究结果提示了乙肝患者自身因素HLA-DR基因多态性可对乙肝患者个体化治疗方案的确定提供帮助。

Objective Based on the analysis of relevance between human leukocyte antigen DR（HLA-DR）antigen and anti HBV therapeutic,to explore personal influencing factors of lamivudine treatment of chronic hepatitis B.Methods Observe and compare HBeAg positive chronic hepatitis B and negative each 160whole blood specimens and clinical data;By PCR-SSP method to detect HLA-DR antigen gene locus in patients with information;Analysis of HLADR test site information correlation with sustained virological response in patients treatment with Lamivudine.Results Sustained virological response ability of HBeAg positive hepatitis B patients is poorer,that is to say,the hepatic function and number of viral replication of patients who continued taking lamivudine were over and over again;There are differences in HLA-DR gene distribution between HBeAg positive and negative after taking lamivudine：Gene frequency（GF：0.217;0.141;0.045;0.22）of DR3/7/8/14in HBeAg positive patients was obviously higher than that of HBeAg negative patients（GF：0.006;0.038;0.006;0.055）（P0.01）,while,the gene frequency（GF：0.035;0.029） of HLA-DR4/13is obviously lower than the HBeAg negative patients（GF：0.193;0.225）（P0.01）.Conclusion HLA-DR3/7has promote HBV persistent infection reduce lamivudine therapeutic effect,while HLA-DR4/13have promote HBV clearance effects,and the correlation between HLA-DR8/14and anti HBV remains to be proven.Research results reveal that hepatitis B patient＇s own factors of HLA-DR gene polymorphism provide help to determine the individualized treatment.