乙型肝炎病毒P区耐药突变与基因型及临床相关性分析

Correlation of mutations of HBV precore region in hepatitis B patient with HBV genotype and drug resistance

目的探讨HBV的P基因耐药突变的分布特征以及与基因型、临床的相关性。方法对慢性乙肝患者的血液样本进行P基因核苷类似物作用靶区进行聚合酶链反应,扩增产物进行测序,比较序列差异性,同时对其进行基因分型检测。结果 79例乙型肝炎患者共检测出B基因型61例(79.2%),C基因型18例(20.8%)。通过对HBV-DNA进行P区测序表明耐药突变以拉米夫定耐药为主,为27例(51.9%);其中B基因型对拉米夫定和阿德福韦的耐药率分别为31.1%(19/61)和9.8%(7/61),二者交叉耐药率为6.6%(4/61);而C基因型对拉米夫定和阿德福韦的耐药率分别为44.4%(8/18)和22.2%(4/18),二者交叉耐药率为16.7%(3/18),明显高于B型基因(P<0.05)。慢性肝炎患者中,B型显著多于C型,为89.4%(59/66);肝癌、肝硬化等重症中,B型感染者则明显少于C型感染者,为15.4%(2/13)(P<0.05)。结论 79例患者HBV基因型以B型为主,C型次之,耐药突变主要以拉米夫定耐药为主,临床与基因型及耐药突变有显著性关联。

Objective To study the correaltion of mutations in the HBV precore region of hepatitis B virus（HBV）DNA with HBV genotype and drug resisntace.Methods The HBV HBV precore region in serum samples from hepatitis B patients were detected by polymerase chain reaction PCR）and HBV gene sequencing and typing were performed after amplification.Results HBV genotype in 79 hepatitis B patients were detected,61（79.2%）were genotype B,18（20.8%）were genotypes C.The resisntace to lamivudine was 51.9%（27/71）highest among the four resistance drug.The resisant rates of HBV genotype B to lamivudine and adefovir were 31.1%（19/61）and 11.5%（7/61）,while the cross drug resistant mutations to lamivudine and adefovir was 6.6%（4/61）.The resistance of HBV genotype C to lamivudine and adefovir were 44.4%（8/18）and adefovir 22.2%（4/18）,and the cross drug resistant mutations to lamivudine and adefovir was16.7%（3/18）significantly higher than tha of HBVgenotype B（P0.05）.HBV genotype B cooupied 89.4%（59/66）among the patients with the chronic hepatitis,significantly higher than the genotype C（10.6%）,While HBV genotype Bwas observed in 15.4%（2/13）of the patients with the hepatic cirrhosis or hepatic cancer,significantly lower than that of HBV genotype C（84.6%）（P0.05）.Conclusion The HBV genotypes in patients with HBV-related chronic liver disease were mainly type B,and then type C.The main resistant mutations was lamivudine mutations in the precore region of HBV DNA.There was significant difference for genotype distribution among patients with HBV-related the chronic hepatitis,hepatic cirrhosis and hepatic cancer.