CAJ | 학술논문

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.
목적 관찰랍미부정치료후무량호응답적만성을형간염환자HBV P구변이정황여기인형적관계.방법 대631례랍미부정치료후무량호응답적만성을형간염환자진행연구.통과형광정량PCR혹핵산측서학정HBV기인형,직접측서관찰P구돌변,실시형광정량PCR방법검측환자병독재량,비교불동기인형환자적HBV DNA수평급HBV P구변이정황.계량자료채용성조설계자료t검험,계수자료채용x~2검험혹Fisher정학검험.결과 631례만성을형간염환자중,B기인형HBV감염자272례,C기인형감염자359례,C기인형감염자환자년령위(39.1±11.4)세,명현대우B기인형감염환자적(33.7±9.7)세(t=-6.55,P<0.01).C기인환자병독재량위(5.96±1.22)log_(10)고패/ml,고우B기인형환자적(5.58±1.21)log_(10)고패/ml,t=-2.01,P<0.05.A181V/T변이재C기인형적발생솔고우B기인형(0.4%비5.3%,χ~2=12.23,P<0.01),M204I/V,L180M、T184A/G/I/S、S202G/I화V173L변이발생솔재B、C기인형지간차이무통계학의의(P치균>0.05).M204I재B기인형적발생솔위20.6%,고우C기인형적13.9%(χ~2=4.91,P<0.05);M204V화M201Ⅳ변이재B、C기인형중적발생솔차이무통계학의의(χ~2치분별위1.70화2.21,P치균>0.05).랍미부정내약발생솔재B、C기인형간차이무통계학의의(χ~2=0.00,P>0.05).결론 랍미부정상견내약위점재B、C기인형지간무명현차이,단시C기인HBV감염환자병독재량고우B기인형HBV감염환자;M204I변이재B기인형중출현빈솔고우C기인형,랍미부정가용혹개용아덕복위지후가능회사A181V/T변이재C기인형출현적개솔고우B기인형;년령、면역인소화비상견위점적변이혹허시영향랍미부정료효적중요인소.
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.