阿德福韦酯单药治疗的慢乙肝患者聚合酶RT区变异位点及临床意义

摘要

Objective A study on the loci variation characteristics of polymerase on area RT and it's clinical significance while a failure using Adefovir monotherapy antiviral treatment,by analyzing the HBV polymerase reverse transcription (RT) gene sequence of the serum from the chronic hepatitis B patients.Method By using retrospective analysis on the loci variation characteristics,clinical significance of polymerase on area RT and follow-up data from the 44 patients identified genetic mutations through the gene sequence of the HBV polymerase area RT,who had a virus re-activation after getting ADV mono therapy antiviral treatment.Result The 44 patients with Adefovir mono therapy,who had the mutation in area RT with the shortest treatment time eight months,up to five years,an average of(32.2 ± 6.7) months.The level fluctuations of the virus is between 103 copies/ml-108 copies/ml.After virological breakthrough,in these 44 cases,11 as A181T (25.0％),8 as A181V (18.2％),10 as 181T/N236T(22.7％),6 as A181V/N236T (13.6％),9 as N236T(20.4％); 40 cases (90.9％) appeared a biochemistry breakthrough,alanine aminotransferase index fluctuation during 37 IU/L-946 IU/L; Remedial treatment using combination lamivudine 23 cases,6 patients with jointing entecavir,than,1 case for jointing telbivudine,change single drug lamivudine in 4 cases,10 cases of single drug entecavir.Prognosis of severe disease (3 cases),and through the remedial treatment,42 cases was recovered.Conclusion ① RT area A181T (A181T/ N236T) variation accounted about a half of total(47.7％),after the drug resistance of the adefovir,2 years of follow-up,the incidence of liver cancer shows a higher trend than patients without A181T.②Conditions allowed,strong inhibitory effect medicines during tinitial therapy should be preferred,to low the incidence of drug-resistant HBV drug,avoid adverse events.%目的 通过对慢性乙型肝炎(CHB)患者血清HBV聚合酶逆转录(RT)区基因序列分析,探讨阿德福韦酯(ADV)单药抗病毒治疗失败,聚合酶RT区变异位点特点及临床意义.方法 采用回顾性分析方法,对接受阿德福韦单药抗病毒治疗出现病毒学突破,经聚合酶RT基因测序,证实存在基因突变的44例患者的聚合酶RT区变异位点、临床特点及随访资料进行分析.结果 44例阿德福韦酯单药治疗患者,至出现RT区变异最短治疗时间8个月,最长5年,平均(32.2±6.7)个月.出现病毒学突破后,病毒水平波动在103拷贝/ml～108拷贝/ml之间；变异位点A181T 11例(25.0％)、A181V 8例(18.2％)、A181T/N236T 10例(22.7％)、A181V/N236T 6例(13.6％)、N236T9例(20.4％)；出现生化学突破40例(90.9％),ALT指标波动在37 IU/L～ 946 IU/L;挽救治疗采用联合拉米夫定23例、联合恩替卡韦6例,联合替比夫定1例,改单药拉米夫定4例,改单药恩替卡韦10例.预后出现疾病重症化3例,经挽救治疗病情得到恢复41例.结论 ①阿德福韦单药耐药RT区A181T(A181T/N236T)变异约占半数(47.7％),随访2年,其肝癌发生率呈现高于非A181T患者趋势.②条件允许,初始治疗应首选HBV抑制作用强、耐药发生率低的药物,避免疾病重症化或肝癌等不良事件发生.