核苷(酸)类似物治疗对乙型肝炎病毒感染者聚合酶区基因变异的影响

Mutation of hepatitis B viral polymerase motif in patients with chronic hepatitis B receiving nucleos(t)ides treatment

目的分析不同核苷(酸)类似物治疗的乙型肝炎病毒感染者乙型肝炎病毒P基因逆转录酶区变异特点。方法采用直接测序法对471例慢性乙型肝炎病毒感染者乙型肝炎病毒P基因逆转录酶区进行测序,比较未曾应用核苷(酸)类似物(第1组)、曾经应用核苷(酸)类似物停药(第2组)和正在应用核苷(酸)类似物(第3组)治疗患者基因突变的特点。结果在第1组、第2组和第3组中分别检出耐药相关错义变异6例(2.0%)、4例(8.2%)和50例(38.5%),同义变异分别为25例(8.5%)、5例(10.2%)和20例(15.4%);在第3组患者中,错义变异组、同义变异组和未变异组血清HBV DNA分别为5.58±1.36lgcopies/ml、5.27±1.05lgcopies/ml和4.98±1.50 lgcopies/ml,差异无统计学意义(P>0.05)。结论不同核苷(酸)类似物治疗的乙型肝炎病毒感染者体内病毒耐药变异株存在的意义还需要进一步研究。

Objective To investigate the mutation of hepatitis B viral polymerase motif in patients with chronic hepatitis B receiving nucleos （t）ides treatment. Method The HBV polymerase reverse transcriptase genes in 481 patients with chronic hepatitis B infection was analysed by direct sequencing. The patients were divided into 3 groups：never applying to nucleoside analogue（NA,group 1）,applying to NA before （group 2） and applying to NA at the moment of study （group 3）. Results The missense variations in group l, 2 and 3 were found in 6 （2.0%）,4（8.2%） and 50（38.5%）,while the homonymy variations in group 1,2 and 3 were found in 25（8.5%）,5 （10.2%）and 20 （15.4%）,respectively;Out of group 3, the serum HBV DNA levels were 5.58±1.361gcopies/ml in patients with missense variation , 5.27 ±1 .051gcopies/ml in with homonymy variation and 4.98±1.501gcopies/ml in without variation,respectively （P〉O.05）. Conclusion Further investigation of HBV variation may help solve the problem of drug resistance in patients with hepatitis B.