摘要
目的研究慢性乙型肝炎(CHB)患者在应用核苷(酸)类似物[NA(s)]治疗过程中出现病毒学突破/反弹的临床特点及乙肝病毒(HBV)聚合酶基因突变模式。方法采用PCR产物直接测序法,对2008年10月-2011年5月在北京佑安医院门诊及住院部接受NA(s)抗病毒治疗过程中出现病毒学突破/反弹的70例CHB患者血清进行测序,回顾性分析其HBV逆转录基因的耐药突变模式及临床特点。结果 70例患者应用NA(s)中位治疗时间21(12～65)个月;HBV DNA定量平均水平(5.26±1.57)logcopies/ml;其中检测到HBV逆转录酶基因耐药的40(40/70)例,单NA(s)药耐药的30(30/40)例,多药耐药(MDR)的10例(10/40);出现生化学突破的31例;出现MDR的患者均有多NA(S)用药经历,与单药耐药比较差异有统计学意义(P<0.05);生化学反弹患者的HBV DNA定量水平高于无生化学反弹患者(P<0.05);检测出HBV逆转录酶耐药位点患者的HBV DNA水平高于未检测出耐药位点者(P<0.05);单药耐药与MDR患者HBV DNA水平及ALT水平差异无统计学意义(P>0.05)。结论序贯多NA(s)抗病毒治疗可选择出多药耐药;多药耐药(MDR)与单药耐药患者生化学及HBV DNA水平无明显差异。
Objective To investigate the clinical features and mutation p;,tterns of HBV polymerase gene in patients with chronic hepatitis B （CHB） after the emergence of drug-resistance during Nucleos （t） ide analogues （NA） therapy. Methods The direct sequencing of PCR product was conducted to study HBV P gene RT region. 70 CHB patients with virus breakthrough/re- bound in nucleos（t）ide analogues treatment were selected from outpatients and hospitalized patients of CHB with A（ s） -resist- ant in the Beijing Youan hospital from Oct. 2008 to May 2011. The clinical features after the emergence of NA（s） -resistant muta- tions were retrospectively analyzed. Results The median time duration of NA （s） treatment was 21 （ 12 - 65 ） months. The medi- an level of serum HBV DNA was（5.26 ± 1.57） logcopies/ml. 40（40/70） patients had HBV-reverse transcriptase resistance mu- tations. 30 （30/40）patients had mono-drug-resistance. 10 （10/40）patients had multiple drug resistant（MDR）. 31 patients had bi- ochemical breakthrough. The patients with MDR all had muhi-NA（s） administration experience, and had significant difference as compared with patients with single-drug resistant（P 〈 O. 05）. HBV DNA levels of in patients with biochemical rebound was higher than that in patients without biochemical rebound（P 〈0.05）. HBV DNA levels in patients with resistance mutations was higher than those without （P 〈 0.05）. The difference in levels of HBV DNA levels and ALT were not significant between the single-drug resistant and the multidrug-resistant patients （ P 〉 0.05 ）. Conclusion The sequential therapy with nucleos （t） ide analogues （NAs） can screen out the multidrug-resistant virus. The biochemistry index and HBV DNA level are not significantly different between the single-drug resistant and the multidrug-resistant patients.
出处
《中华全科医学》
2012年第3期364-365,共2页
Chinese Journal of General Practice
