中华临床感染病杂志
中華臨床感染病雜誌
중화림상감염병잡지
CHINESE JOURNAL OF CLINICAL INFECTIOUS DISEASES
2015年
2期
139-142
,共4页
高国生%翁彭剑%许小敏%董飞波%颜华东%胡爱荣
高國生%翁彭劍%許小敏%董飛波%顏華東%鬍愛榮
고국생%옹팽검%허소민%동비파%안화동%호애영
肝炎,乙型,慢性%恩替卡韦%抗药性%DNA突变分析
肝炎,乙型,慢性%恩替卡韋%抗藥性%DNA突變分析
간염,을형,만성%은체잡위%항약성%DNA돌변분석
Hepatitis B,chronic%Entecavir%Drug resistance%DNA mutation analysis
目的 分析慢性乙型肝炎病毒(HBV)感染者恩替卡韦(ETV)耐药突变特征.方法 采用实时荧光定量聚合酶链反应(PCR)方法对2010年2月至2014年5月宁波市第二医院44例ETV耐药的慢性HBV感染者的血清HBV多聚酶区进行扩增,并对PCR产物进行直接测序.采用SPSS 16.0软件分析ETV耐药相关位点的突变发生率,及其与基因型及临床特征的相关性.结果 44例患者的基因突变模式以rtS202G/I (52.28％,23/44)为主,其次为rtT184A/G/l/S(36.36％,16/44)和rtM250V/L(11.36％,5/44).共检出9种基因突变模式,其中以rtL180+ rtM204V+ rtS202G/l和rtL180+ rtM204V+ rtT184A/G/I/S最为常见,分别占38.64％ (17/44)和27.27％ (12/44).基因B型和C型患者ETV耐药突变位点分布差异有统计学意义(x2=12.294,P ＜0.01).比较不同基因突变模式感染患者的临床资料发现,发生rtT184A/G/I/S突变的患者肝脏损害程度较其他患者更为严重(x2=14.499,P＜0.01),而发生rtM250V/L突变的患者HBeAg阳性率较其他模式低(x2=10.057,P＜0.01).结论 对ETV耐药的慢性HBV感染者血清HBV多聚酶区基因突变以rtL180+ rtM204V+ rtS202G/I较为常见,且不同基因突变模式与基因分型、肝脏损害程度和HBeAg阳性率可能相关.
目的 分析慢性乙型肝炎病毒(HBV)感染者恩替卡韋(ETV)耐藥突變特徵.方法 採用實時熒光定量聚閤酶鏈反應(PCR)方法對2010年2月至2014年5月寧波市第二醫院44例ETV耐藥的慢性HBV感染者的血清HBV多聚酶區進行擴增,併對PCR產物進行直接測序.採用SPSS 16.0軟件分析ETV耐藥相關位點的突變髮生率,及其與基因型及臨床特徵的相關性.結果 44例患者的基因突變模式以rtS202G/I (52.28％,23/44)為主,其次為rtT184A/G/l/S(36.36％,16/44)和rtM250V/L(11.36％,5/44).共檢齣9種基因突變模式,其中以rtL180+ rtM204V+ rtS202G/l和rtL180+ rtM204V+ rtT184A/G/I/S最為常見,分彆佔38.64％ (17/44)和27.27％ (12/44).基因B型和C型患者ETV耐藥突變位點分佈差異有統計學意義(x2=12.294,P ＜0.01).比較不同基因突變模式感染患者的臨床資料髮現,髮生rtT184A/G/I/S突變的患者肝髒損害程度較其他患者更為嚴重(x2=14.499,P＜0.01),而髮生rtM250V/L突變的患者HBeAg暘性率較其他模式低(x2=10.057,P＜0.01).結論 對ETV耐藥的慢性HBV感染者血清HBV多聚酶區基因突變以rtL180+ rtM204V+ rtS202G/I較為常見,且不同基因突變模式與基因分型、肝髒損害程度和HBeAg暘性率可能相關.
목적 분석만성을형간염병독(HBV)감염자은체잡위(ETV)내약돌변특정.방법 채용실시형광정량취합매련반응(PCR)방법대2010년2월지2014년5월저파시제이의원44례ETV내약적만성HBV감염자적혈청HBV다취매구진행확증,병대PCR산물진행직접측서.채용SPSS 16.0연건분석ETV내약상관위점적돌변발생솔,급기여기인형급림상특정적상관성.결과 44례환자적기인돌변모식이rtS202G/I (52.28％,23/44)위주,기차위rtT184A/G/l/S(36.36％,16/44)화rtM250V/L(11.36％,5/44).공검출9충기인돌변모식,기중이rtL180+ rtM204V+ rtS202G/l화rtL180+ rtM204V+ rtT184A/G/I/S최위상견,분별점38.64％ (17/44)화27.27％ (12/44).기인B형화C형환자ETV내약돌변위점분포차이유통계학의의(x2=12.294,P ＜0.01).비교불동기인돌변모식감염환자적림상자료발현,발생rtT184A/G/I/S돌변적환자간장손해정도교기타환자경위엄중(x2=14.499,P＜0.01),이발생rtM250V/L돌변적환자HBeAg양성솔교기타모식저(x2=10.057,P＜0.01).결론 대ETV내약적만성HBV감염자혈청HBV다취매구기인돌변이rtL180+ rtM204V+ rtS202G/I교위상견,차불동기인돌변모식여기인분형、간장손해정도화HBeAg양성솔가능상관.
Objective To investigate hepatitis B virus (HBV) gene mutations related to entecavir (ETV)-resistance in patients with chronic HBV infections.Methods Serum samples were collected from 44 patients with chronic HBV infections and resistant to ETV treatment who were admitted in Ningbo No.2 Hospital during February 2010 and May 2014.The HBV polymerase regions were amplified by real-time fluorescent quantitative polymerase chain reaction (PCR) method,and the PCR products were analyzed with direct sequencing.SPSS 16.0 was used to assess the frequency of HBV polymerase gene mutations,and its relation to the viral genotype and clinical features.Results The most common HBV polymerase gene mutation was rtS202G/I (52.28％,23/44),followed by rtT184A/G/I/S (36.36％,16/44) and rtM250V/L (11.36％,5/44).Nine mutation patterns were detected,in which rtL180 + rtM204V + rtS202G/I (38.64％,17/44) and rtL180 +rtM204V + rtT184A/G/I/S (27.27％,12/44) were the most frequent ones.The difference in gene mutations between genotype B and C was of statistical significance (x2=12.294,P ＜0.01).Patients carrying rtT184A/G/I/S mutations were associated with worse liver function (x2 =14.499,P ＜ 0.01),and those carrying rtM250V/L mutations were associated with lower HBeAg positive rate (x2 =10.057,P ＜ 0.01).Conclusions rtL180M + rtM204V + rtS202G/I is the most common HBV polymerase gene mutation related to ETV resistance in patients with chronic HBV infections.Different gene mutations may be associated with HBV genotypes,severity of liver damages,and HBeAg positive rate.
