CAJ | 학술논문

目的:对比分析慢性乙型肝炎病毒(HBV)感染者阿德福韦酯(ADV)诱导耐药突变与预存耐药突变的临床及分子生物学特点.方法:ADV耐药突变的慢性HBV感染者88例,采用基因测序的方法对患者的血清标本进行P区耐药基因测序,同时检测HBV基因型、HBV血清学标志物及HBV-DNA.结果:88例中,发现ADV预存耐药突变9例(10.23%),其中部分患者(4/9,44.44%)曾接受过不规范的抗病毒治疗;诱导耐药组中以rtA181T突变及单个位点突变为主(41/79,51.9%;61/79,77.22%)、完全突变株40例、突变株与野生株共存39例,而预存耐药组以rtN238T突变、多位点突变以及突变株与野生株共存为主;诱导耐药组的HBV-DNA为(5.15±1.23)log10拷贝/mL,预存耐药组为(6.45±0.97)log10拷贝/mL(t=-3.05,P=0.003);诱导耐药组中终末期肝病患者占40.51%(32/79),而预存耐药组均为终末期肝病患者(P=0.001);两组在性别、年龄、E抗原状态及HBV基因型构成方面比较差异无统计学意义(P>0.05).结论:在未经ADV抗病毒治疗的慢性HBV感染者中可能存在ADV预存耐药突变;诱导耐药的准种变异经过筛选后变得较单一,而预存耐药的准种变异较复杂;终末期肝病患者中可能存在各种抗病毒药物的预存耐药突变;发生ADV诱导突变后的HBV-DNA复制水平常较低;患者应该接受和执行规范的抗病毒治疗和优化治疗,以实现预防耐药,避免挽救治疗.
목적:대비분석만성을형간염병독(HBV)감염자아덕복위지(ADV)유도내약돌변여예존내약돌변적림상급분자생물학특점.방법:ADV내약돌변적만성HBV감염자88례,채용기인측서적방법대환자적혈청표본진행P구내약기인측서,동시검측HBV기인형、HBV혈청학표지물급HBV-DNA.결과:88례중,발현ADV예존내약돌변9례(10.23%),기중부분환자(4/9,44.44%)증접수과불규범적항병독치료;유도내약조중이rtA181T돌변급단개위점돌변위주(41/79,51.9%;61/79,77.22%)、완전돌변주40례、돌변주여야생주공존39례,이예존내약조이rtN238T돌변、다위점돌변이급돌변주여야생주공존위주;유도내약조적HBV-DNA위(5.15±1.23)log10고패/mL,예존내약조위(6.45±0.97)log10고패/mL(t=-3.05,P=0.003);유도내약조중종말기간병환자점40.51%(32/79),이예존내약조균위종말기간병환자(P=0.001);량조재성별、년령、E항원상태급HBV기인형구성방면비교차이무통계학의의(P>0.05).결론:재미경ADV항병독치료적만성HBV감염자중가능존재ADV예존내약돌변;유도내약적준충변이경과사선후변득교단일,이예존내약적준충변이교복잡;종말기간병환자중가능존재각충항병독약물적예존내약돌변;발생ADV유도돌변후적HBV-DNA복제수평상교저;환자응해접수화집행규범적항병독치료화우화치료,이실현예방내약,피면만구치료.
Objective: To explore the molecular epidemiological and clinical characteristics of induced resistance mutations and pre-existing resistance mutations related to adefovir dipivoxil (ADV) in patients with chronic hepati?tis B virus (HBV) infection. Methods: The data of 88 chronic HBV-infected patients with resistance mutations related to ADV from June 2008 to August 2010 were retrospectively analyzed. The gene resistance mutations of HBV P region were analyzed by gene sequencing, and the HBV genotypes, HBV serum markers, and HBV DNA levels were also analyzed. Results: There were 9 patients with pre-existing resistance mutations in 88 patients (10.23%) and 4 out of 9 (44.44%) had ill-formed usage of antiviral drugs except ADV. Patients in induced muta?tion group mostly had rtA181T mutation and single mutated site (41/79,51.9%;61/79,77.22%);40 patients had com?plete mutation and 39 had mutation co-existence with wild strain. Patients with pre-existing mutations mostly had rtN238T mutation at multiple sites (5/9,55.56%) and co-existence mutations (8/9,88.89%).The levels of HBV DNA were 5.15 ± 1.23 log10 copies/ml in the induced mutation group and 6.45 ± 0.97 log10 copies/ml in the pre-existing mutation group (t= -3.05, P=0.003). There were 32 patients (32/79,40.51%) with end-stage liver dis?eases in the induced mutation group compared with all patients (9/9,100%) in the pre-existing mutation group (P=0.001). No statistically significant differences was noted in constituent ratio of age,sex,HBeAg and HBV genotypes between the 2 groups (P>0.05). Conclusion: There may be some patients with pre-existing resistance mutations related to ADV in ADV treatment-naive patients. The HBV quasispecy mutations became unified after selection of ADV, whereas they were complex in the pre-existing mutation group. The pre-existing mutations related to nu?cleos(t)ide analogues maybe exist in patients with end-stage liver diseases. The levels of HBV DNA are always lower when patients have induced resistance mutation related to ADV. It is important for patients to accept and to execute normative usage of antiviral drugs and optimal treatment to reach the aim for preventing resistance and avoiding salvage therapy.