南通地区乙型肝炎病毒P区耐药突变与基因型及其临床意义

目的 探讨南通地区乙型肝炎病毒P区耐药基因突变特征与基因型,为临床合理用药提供科学依据。方法 选择158例经核苷(酸)类似物治疗至少2年以上慢性乙型肝炎(CHB)患者和30例未接受过核苷(酸)类似物治疗的CHB患者作为研究对象,采用PCR产物直接测序法检测HBV P区耐药基因和基因型,同时观察三种主要突变模式与ALT和HBV DNA水平的关系。结果 158例CHB患者检出B基因型42例(26.58%),C基因型116例(73.42%)。131例发生P区不同位点突变,突变率为82.91%。共检出11个HBV突变位点,主要突变位点是M204I,L180M,M204V,A181V和A181T,耐药频率依次为41.14%,37.34%,22.15%,11.39%和10.13%,11个突变位点有21种突变模式。拉米夫定(LAM)耐药相关突变中以L180M和M204V合并出现为主,其次以M204I单独出现; 阿德福韦酯(ADV)耐药相关突变中以A181V为主; 恩替卡韦(ETV)耐药率较低。结论 南通地区HBV基因型以B和C型为主,C型为优势基因型; 耐药突变主要集中在拉米夫定和阿德福韦酯耐药相关的突变位点,而恩替卡韦耐药率较低。多位点耐药突变检测有助于及时发现病毒耐药,更好地指导临床治疗。

Drug Resistance Mutations and Genotypes of Hepatitis BVirus P in Nantong Area and Its Clinical Significance

Objective To investigate the mutation characteristics and genotype of hepatitis B virus resistance gene in Nantong area,andprovide scientific basis for clinical rational drug.Methods A total of 158 cases of chronic hepatitis B(CHB)patients who were received with nucleos(T)ide analogues therapy for at least 2 years as the research object,and 30 cases of CHB patients who were not received nucleos(T)ide analogues for the treatment as the control group.PCR-sequencing method was used to detect the HBV P resistant gene and genotype,meanwhile,observe the relationshipbetween three main mutation model and the levels of ALT and HBV DNA was also investigated.Results B genotype was detected in 42(26.58%)out of 158 CHB patients,and 116 cases(73.42%)were C genotype.A total of131 patients with different site mutations in P region,the mutation rate were 82.91%.There were totally 11 HBV mutation sites,including the main mutation site:M204I,L180M,M204V,A181V and A181T,the frequency of drug resistance were41.14%,37.34%,22.15%,11.39% and 10.13%,respectively.Moreover,11 mutation sites had 21 mutation patterns.In lamivudine(LAM)resistance associated mutations,the L180M and M204V sites were mainly co-occurrence,followed by M204Ialone.In adefovir dipivoxil(ADV)resistance associated mutations,A181V was the main mutation site.Whereas,the drug resistance rate of entecavir(ETV)waslow.Conclusion The main genotypes of HBV were type B and C in Nantong area,and C type was the dominant genotype.The resistance mutations mainly concentrated in LAM and ADV resistance associated mutations,while the resistance rate of ETV was low.Multi-locus drug-resistant mutation detection may help to detect viral resistance and guide clinical treatment better.