深圳地区乙型肝炎病毒基因型分布与核苷类药物治疗后相应突变位点筛查的研究

目的了解深圳地区乙肝病毒基因型分布特点以及拉米夫定（LMV）和阿德福韦（ADV）两种药物治疗后相关指标变化情况。方法276例HBeAg阳性患者采用实时荧光定量PCR法检测HBV DNA的含姑，免疫化学发光法检测HBeAg的相对含量．DNA反向斑点杂交芯片技术检测HBV DNA基因型与LMV常见耐药位点、ADV常见耐药位点，全自动生化测定谷丙转氦酶。随机选取未发牛以上突变位点慢性病例各96例，分别以LMV和ADV两种药物进行治疗，于治疗前和治疗3、12个月检测HBV DNA、HBeAg及ALT的含量，并在治疗12个月时筛查2组耐药突变位点。结果276例HBeAg阳性标本有270例可以进行分型，其中B型138例（50．0％）、C型96例（34．8％）、D型10例（3．6％）、B＋C混合型26例（9．4％）、末分碰6例（2．2％）。在治疗3个月时LMV组HBV DNA与HBeAg含量下降速度和阴转率以及ALT下降明显高于ADV组（P〈0．05）；但在治疗第12个月时LMV组HBV DNA含节下降速度和阴转率反而低于ADV组。LMV组有20例发生耐药他点，而ADV组无一例发生位点突变。结论深圳地区乙肝分型主要以B、C两型为主．B型略占优势，B＋C混合型也占有一定比例，核苷类药物LAM及ADV单药治疗慢性乙肝患者均有较好的疗效，但两种药物比较，短期效果LAM优于ADV，随着用药时间延长，耐药突变基因的逐渐出现，ADV长期治疗效果反而要优于LAM。

Research of HBV genotype distribution and gene mutation site screening after lamivudine and adefovir antiviral treatment in Shenzhen area

Objective To understand the distribution of hepatitis B genotypes in Shenzhen area and the changes of its indicators after lamivudine (LMV) and adefovir antiviral (ADV) treatment. Methods The content of HBV DNA was measured with real-time fluorescent RT-PCR and the relative amount of HBeAg was determined with chemiluminescent immunoassay (CLIA) in 276 patients with HBeAg positive. Reverse dot blot hybridization DNA chip method was applied to detecting HBV DNA genotypes, common LMV-resistance sites (rtl80M + rt204V + rt204I + r207I) and common ADV-resistance sites (rtA181V+rtA236T)) fully antomatic biochemical analyzer was applied to examining alanine aminotransferase (ALT). The DNAs of HBV and HBeAg as well as ALT were detected before and 3,12 months after therapy with LMV and ADV. Two groups of mutational sites were screened 12 montha after treatment. Results All 276 samples were classified as genotype B (50. 0%), genotype C (34. 8%), genotype D (3. 6%), genotype (B + C) (9. 4%), and undetermined type (2. 2%). There were significant differences of decline on levels of DNA of HBV, HBeAg and ALT after antiviral treatment between lamivudine and adefovir for 3 months (P<0. 05). However,the therapeutic effect of lamivudine was weaker than that of adefovir 12 months after therapy. Resistance site mutation occurred in 20 cases of LMV group,whereas no site mutation occurred in ADV group.Conclusion The major genotypes in Shenzhen area are genotype B and C,genotype B is a little dominant,and mixed genotypes of B and C accounts for a definite proportion.Although the short-term therapeutic effect of LMV is superior to ADV,the long-term antiviral efficacy of ADV is better in patients with chronic hepatitis B as a result of gradual appearance of resistance mutational genes.