拉米夫定治疗无良好应答患者乙型肝炎病毒P区突变与基因型的关系

目的 观察拉米夫定治疗后无良好应答的慢性乙型肝炎患者HBV P区变异情况与基因型的关系.方法 对631例拉米夫定治疗后无良好应答的慢性乙型肝炎患者进行研究.通过荧光定量PCR或核酸测序确定HBV基因型,直接测序观察P区突变,实时荧光定量PCR方法检测患者病毒载量,比较不同基因型患者的HBV DNA水平及HBV P区变异情况.计量资料采用成组设计资料t检验,计数资料采用x~2检验或Fisher精确检验.结果 631例慢性乙型肝炎患者中,B基因型HBV感染者272例,C基因型感染者359例,C基因型感染者患者年龄为(39.1±11.4)岁,明显大于B基因型感染患者的(33.7±9.7)岁(t=-6.55,P<0.01).C基因患者病毒载量为(5.96±1.22)log_(10)拷贝/ml,高于B基因型患者的(5.58±1.21)log_(10)拷贝/ml,t=-2.01,P<0.05.A181V/T变异在C基因型的发生率高于B基因型(0.4%比5.3%,χ~2=12.23,P<0.01),M204I/V,L180M、T184A/G/I/S、S202G/I和V173L变异发生率在B、C基因型之间差异无统计学意义(P值均>0.05).M204I在B基因型的发生率为20.6%,高于C基因型的13.9%(χ~2=4.91,P<0.05);M204V和M201Ⅳ变异在B、C基因型中的发生率差异无统计学意义(χ~2值分别为1.70和2.21,P值均>0.05).拉米夫定耐药发生率在B、C基因型间差异无统计学意义(χ~2=0.00,P>0.05).结论 拉米夫定常见耐药位点在B、C基因型之间无明显差异,但是C基因HBV感染患者病毒载量高于B基因型HBV感染患者;M204I变异在B基因型中出现频率高于C基因型,拉米夫定加用或改用阿德福韦酯后可能会使A181V/T变异在C基因型出现的概率高于B基因型;年龄、免疫因素和非常见位点的变异或许是影响拉米夫定疗效的重要因素.

Polymerase region mutations and hepatitis B virus genotypes in chronic hepatitis B patients with poor response to lamivudine

Objective To investigate the mutations in Polymerase region and hepatitis B virus (HBV)genotypes in chronic hepatitis B patients with poor response to Lamivudine treatment.Methods 631 chronic hepatitis B patients with poor response to Lamivudine were recruited in this study.Real-time PCR and DNA sequencing were used to determine HBV genotypes;direct sequencing was performed to detect mutations,and real-time PCR was used to quantify HBV DNA load.Mutations in polymerase region were investigated in different HBV genotypes.Results 272 patients were infected with HBV of genotype B,and 359 patients were infected with I-IBV of genotype C.The mean age of patients infected with HBV of genotype C(39.1±11.4 years old)were significant higher than that of patients infected with HBV of genotype B(33.7±9.7 years old)(t=-6.55,P < 0.01).The patients infected with FIBV of genotype C had relatively higher FIBV DNA load(5.96±1.22)log_(10) copies/ml]than the patients infected with HBV of genotype B (5.58±1.21)log_(10) copies/ml](t=-2.01,P < 0.05).The overall incidence rate of A181V/T mutation in genotype C(5.3%)was significantly higher than that in genotype B(0.4%)(χ~2=12.23,P < 0.01),but the incidence rate of M204I/V,LI80M,TI84A/G/I/S,S202G/I and V173L mutations was not significantly different between genotype B and C(each P > 0.05).M204I mutation in genotype B(20.6%)was more frequent than that in genotype C(13.9%)(χ~2=4.91,P < 0.05).The Lamivudine resistance mutations were not significantly different between genotype B and genotype C(χ~2=0.00,P > 0.05).Conclusions The incidence rate of lamivudine resistance mutation is not significantly different between genotype B and genotype C,but patients infected with HBV of genotype C have higher HBV DNA load than patients infected with HBV of genotype B.