中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2008年
10期
735-738
,共4页
徐东平%刘妍%成军%李晓东%戴久增%李乐%梁兆玲%白丽%钟彦伟%许智慧%任晓强%张玲霞
徐東平%劉妍%成軍%李曉東%戴久增%李樂%樑兆玲%白麗%鐘彥偉%許智慧%任曉彊%張玲霞
서동평%류연%성군%리효동%대구증%리악%량조령%백려%종언위%허지혜%임효강%장령하
肝炎病毒,乙型%突变%耐药
肝炎病毒,乙型%突變%耐藥
간염병독,을형%돌변%내약
Hepatitis B virus%Mutation%Drug resistance
目的 分析慢性乙型肝炎患者HBV逆转录酶基因与核苷(酸)类似物耐药相关的12个位点上的突变情况及其临床意义.方法 提取血清HBV DNA,扩增HBV逆转录酶基因,对PCR产物进行DNA双向测序,对测序成功的样本进行基因型分析.检测逆转录酶基因12个位点上的碱基突变情况,分析不同核苷(酸).类似物使用情况、患者的耐药相关突变情况及不同核苛(酸)类似物耐药的突变形式. 结果 检出拉米夫定耐药突变63例,阿德福韦耐药突变10例,恩替卡韦耐药突变8例,替比夫定耐药突变1例.拉米夫定耐药突变中以M204V和M204I最常见,前者通常伴随L180M突变,后者常单独出现,阿德福韦耐药中以N236T±A181位碱基替换为主;恩替卡韦耐药突变发生在拉米夫定耐药基础上,以T184位碱基替换为主;替比夫定的耐药突变为M204I.少数未接受过核苷(酸)类似物治疗的患者也可检出耐药相关突变.结论 检测HBV逆转录酶基因多位点耐药相关突变,有助于临床及时发现和确认乙型肝炎患者是否存在HBV耐药,合理进行抗病毒治疗.
目的 分析慢性乙型肝炎患者HBV逆轉錄酶基因與覈苷(痠)類似物耐藥相關的12箇位點上的突變情況及其臨床意義.方法 提取血清HBV DNA,擴增HBV逆轉錄酶基因,對PCR產物進行DNA雙嚮測序,對測序成功的樣本進行基因型分析.檢測逆轉錄酶基因12箇位點上的堿基突變情況,分析不同覈苷(痠).類似物使用情況、患者的耐藥相關突變情況及不同覈苛(痠)類似物耐藥的突變形式. 結果 檢齣拉米伕定耐藥突變63例,阿德福韋耐藥突變10例,恩替卡韋耐藥突變8例,替比伕定耐藥突變1例.拉米伕定耐藥突變中以M204V和M204I最常見,前者通常伴隨L180M突變,後者常單獨齣現,阿德福韋耐藥中以N236T±A181位堿基替換為主;恩替卡韋耐藥突變髮生在拉米伕定耐藥基礎上,以T184位堿基替換為主;替比伕定的耐藥突變為M204I.少數未接受過覈苷(痠)類似物治療的患者也可檢齣耐藥相關突變.結論 檢測HBV逆轉錄酶基因多位點耐藥相關突變,有助于臨床及時髮現和確認乙型肝炎患者是否存在HBV耐藥,閤理進行抗病毒治療.
목적 분석만성을형간염환자HBV역전록매기인여핵감(산)유사물내약상관적12개위점상적돌변정황급기림상의의.방법 제취혈청HBV DNA,확증HBV역전록매기인,대PCR산물진행DNA쌍향측서,대측서성공적양본진행기인형분석.검측역전록매기인12개위점상적감기돌변정황,분석불동핵감(산).유사물사용정황、환자적내약상관돌변정황급불동핵가(산)유사물내약적돌변형식. 결과 검출랍미부정내약돌변63례,아덕복위내약돌변10례,은체잡위내약돌변8례,체비부정내약돌변1례.랍미부정내약돌변중이M204V화M204I최상견,전자통상반수L180M돌변,후자상단독출현,아덕복위내약중이N236T±A181위감기체환위주;은체잡위내약돌변발생재랍미부정내약기출상,이T184위감기체환위주;체비부정적내약돌변위M204I.소수미접수과핵감(산)유사물치료적환자야가검출내약상관돌변.결론 검측HBV역전록매기인다위점내약상관돌변,유조우림상급시발현화학인을형간염환자시부존재HBV내약,합리진행항병독치료.
Objective To analyze HBV drug-resistant mutations against nucleos(t)ide analogues at 12 reported sites in 340 patients with chronic hepatitis B. Methods Serum HBV DNA was extracted and a nested PCR assay was employed for the reverse transcriptase (RT) gene amplification. Direct sequencing of PCR product was performed. The siguifieance of detected mutations was analyzed in view of clinical data of the patients. Results Drug-resistant mutations were detected in 68 patients taking lamivudine (LAM), 10 taking adefovir (ADV), 8 taking entecavir, and 1 taking telbivudine (LdT). M204V and M204I were the most common LAM-resistant mutations. The former usually emerged with L180M while the latter often emergedalone. N236T ± A 181 substitution was the most frequently seen ADV-resistant mutation. ETV-resistant mu-tations occurred on the basis of LAM-resistant mutations and T 184 change was the most common form. LdT-resistance was observed as M204I. Interestingly, these drug-resistant mutations were detected in a few pa-tients who had not been treated with nucleos(t)ide analogues. Conclusion Detection of HBV drug-resistant mutations at multiple sites of the viral RT gent is valuable for discovering and verifying drug resistance and thus is very helpful in planning anti-HBV therapy.
