中华实验和临床感染病杂志（电子版）
中華實驗和臨床感染病雜誌（電子版）
중화실험화림상감염병잡지（전자판）
CHINESE JOURNAL OF EXPERIMENTAL AND CLINICAL INFECTIOUS DISEASES(ELECTRONIC VERSION)
2014年
3期
403-406
,共4页
杨松%邢卉春%王琦%王笑梅%欧蔚妮%段英%李贲%李玥%刘顺爱%成军
楊鬆%邢卉春%王琦%王笑梅%歐蔚妮%段英%李賁%李玥%劉順愛%成軍
양송%형훼춘%왕기%왕소매%구위니%단영%리분%리모%류순애%성군
阿德福韦酯%耐药%肝炎,乙型,慢性%焦磷酸测序
阿德福韋酯%耐藥%肝炎,乙型,慢性%焦燐痠測序
아덕복위지%내약%간염,을형,만성%초린산측서
Adefovir dipivoxil (ADV)%Resistance%Chronic hepatitis B%Pyrosequencing
目的：明确临床实际工作中阿德福韦酯（ADV）治疗出现病毒学突破患者基因型耐药情况并对耐药相关因素进行分析。方法收集ADV治疗出现病毒学突破患者的血清样本及临床资料，应用PCR产物直接测序法联合焦磷酸测序法进行基因型耐药检测；分析基因型耐药与患者抗病毒治疗经过、基线HBV DNA载量等因素的相关性；并进一步分析rtA181T变异患者的病毒学及生化学指标变化。结果共收集106例ADV治疗出现病毒学突破患者，共检出基因型耐药45例，耐药位点67个；既往LAM等经治换用ADV患者ADV耐药检出率显著高于ADV初治患者（χ2=6.584，P =0.010）；rtA181T耐药变异患者HBV DNA较最低值升高水平显著高于不包含rtA181T变异患者（t=566.000，P=0.014）；包含rtA181T变异患者生化学突破率显著高于不包含rtA181T变异患者（χ2=5.140，P =0.023）。结论本组患者数据提示ADV治疗出现病毒学突破患者基因型耐药发生率约为40%，rtA181位点变异多于rtN236位点变异，rtA181T变异虽抑制耐药株病毒复制，但导致患者出现生化学突破几率并未减少。
目的：明確臨床實際工作中阿德福韋酯（ADV）治療齣現病毒學突破患者基因型耐藥情況併對耐藥相關因素進行分析。方法收集ADV治療齣現病毒學突破患者的血清樣本及臨床資料，應用PCR產物直接測序法聯閤焦燐痠測序法進行基因型耐藥檢測；分析基因型耐藥與患者抗病毒治療經過、基線HBV DNA載量等因素的相關性；併進一步分析rtA181T變異患者的病毒學及生化學指標變化。結果共收集106例ADV治療齣現病毒學突破患者，共檢齣基因型耐藥45例，耐藥位點67箇；既往LAM等經治換用ADV患者ADV耐藥檢齣率顯著高于ADV初治患者（χ2=6.584，P =0.010）；rtA181T耐藥變異患者HBV DNA較最低值升高水平顯著高于不包含rtA181T變異患者（t=566.000，P=0.014）；包含rtA181T變異患者生化學突破率顯著高于不包含rtA181T變異患者（χ2=5.140，P =0.023）。結論本組患者數據提示ADV治療齣現病毒學突破患者基因型耐藥髮生率約為40%，rtA181位點變異多于rtN236位點變異，rtA181T變異雖抑製耐藥株病毒複製，但導緻患者齣現生化學突破幾率併未減少。
목적：명학림상실제공작중아덕복위지（ADV）치료출현병독학돌파환자기인형내약정황병대내약상관인소진행분석。방법수집ADV치료출현병독학돌파환자적혈청양본급림상자료，응용PCR산물직접측서법연합초린산측서법진행기인형내약검측；분석기인형내약여환자항병독치료경과、기선HBV DNA재량등인소적상관성；병진일보분석rtA181T변이환자적병독학급생화학지표변화。결과공수집106례ADV치료출현병독학돌파환자，공검출기인형내약45례，내약위점67개；기왕LAM등경치환용ADV환자ADV내약검출솔현저고우ADV초치환자（χ2=6.584，P =0.010）；rtA181T내약변이환자HBV DNA교최저치승고수평현저고우불포함rtA181T변이환자（t=566.000，P=0.014）；포함rtA181T변이환자생화학돌파솔현저고우불포함rtA181T변이환자（χ2=5.140，P =0.023）。결론본조환자수거제시ADV치료출현병독학돌파환자기인형내약발생솔약위40%，rtA181위점변이다우rtN236위점변이，rtA181T변이수억제내약주병독복제，단도치환자출현생화학돌파궤솔병미감소。
ObjectiveTo investigatethe genotype resistance proifle in patients with real-life chronic hepatitis B who underwent virological breakthrough during adefovirdipivoxil(ADV)treatment and clinical factors related toADV resistance.Methods Theclinical data and serum samples were collected from CHB patients who underwent virological breakthrough duringADV treatment. PCR products direct-sequencing and pyrosequencing were used for detectingADV genotype resistance. Correlation between resistance and treatment history, baseline HBV DNA level etc were analyzed, respectively. Virological and biochemical features of rtA181T resistance were analyzed.Results Total of106 CHB patients were enrolled andADV genotype resistance were found in 45patents while 67ADV resistance mutations were identified. Less resistance were identiifed inADVna?ve patients than that in patients who took lamivudine/ADV sequential therapy (χ2= 6.584,P = 0.010).ADV resistant patients carrying rtA181T mutation had lower level HBV DNA rise from nadir than patients without rtA181T mutation (t= 566.000,P=0.014).More patients with rtA181T mutation underwent biochemical breakthrough than patients without rtA181T mutation (χ2= 5.140, P = 0.023).ConclusionsAbout 40%ADV treated patients who underwent virological breakthrough were identiifed asADV genotype resistance. RtA181 resistance mutation was more common than rtN236 forADV resistance. RtA181T mutation may inhibit HBV replication and cause no less biochemical breakthrough than otherADV resistance mutations.
