Objective To observe the history of antiviral therapy , serological characteristics , and entecavir salvage therapeutic effect in the hepatitis B virus ( HBV) reverse transcriptase ( RT) 181 site T/V mutant patients with chronic hepatitis B.Methods Seventy-one patients with virological breakthrough of nucleoside (acid) analogues (NAs)-resistant hepatitis B were continuously enrolled .Using direct sequencing for HBV sequencing , and we confirmed the presence of HBV reverse transcriptase region 181 site mutation of T/V, including 41 cases of HBV reverse transcriptase region 181 site mutation of T (rtA181T), and 30 cases of HBV reverse transcriptase region 181 site mutation of V (rtA181V).The medi-cation history of NAs in 71 patients was reviewed .The levels of serum ALT , HBsAg, and HBV-DNA were detected and compared in rtA181T and rtA181V patients during virological breakthrough .All patients were treated with entecavir-based antiviral therapy, and then we compared the virological response of rtA 181T and rtA181V patients at 24 and 52 weeks. Results Of the 71 patients, 25 patients were treated with a single antiviral drug (adefovir dipivoxil), and 46 patients with sequential or combined use of multiple NA .When the HBV rtA181T and rtA181V patients had virological breakthrough , the levels of serum ALT were 55 (15, 474) and 49 (16,183) U/mL, respectively, P>0.05; the log10 of HBV-DNA were 5.71 ±1.02 and 6.04 ±0.97, respectively, P<0.05; the log10 of serum HBsAg were 3.36 ±0.50 and 3.64 ± 0.60, P<0.05.Salvage therapy with entecavir was mainly for 24 weeks.The complete virologic response was found in 55 cases (77.5%), including 33 cases (80.5%) of HBV rtA181T patients and 22 cases (73.3%) of HBV rtA181V pa-tients;incomplete virologic response was found in 16 cases (22.5%).After 52 weeks of treatment, the complete virologic response was found in 62 cases (87.3%), including 37 cases (90.2%) of HBV rtA181T patients and 25 cases (83.3%) of HBV rtA181V patients;incomplete virologic response was found in 9 cases (12.7%), and no significant difference was found in the virologic response between the HBV rtA 181T and rtA181V patients (P>0.05).Conclusions Patients with HBV rtA181T/V mutation are mostly treated with sequential or combined with adefovir dipivoxil , lamivudine and other NAs.Serum HBsAg is higher in HBV rtA181V patients than in patients with HBV rtA 181T.The treatment effect of HBV rtA181T/V patients treated with entecavir salvage is satisfactory , but the treatment effect is not different between HBV rtA181T and HBV rtA181V patients.%目的 观察HBV逆转录酶区181位点T/V突变(HBV rtA181T/V)患者的抗病毒治疗史、血清学特点、恩替卡韦挽救治疗效果.方法 连续入组71例已经出现病毒学突破的核苷(酸)类似物(NAs)耐药乙肝患者.均采用直接测序法行HBV测序,且证实存在HBV rtA181T/V,其中HBV rtA181T突变41例、HBV rtA181V突变30例.回顾71例患者的NAs用药史.检测并比较rtA181T、rtA181V患者出现病毒学突破时的血清ALT、HBsAg、HBV-DNA水平.所有患者采用恩替卡韦为主的挽救方案治疗,比较rtA181T、rtA181V患者治疗24、52周时的病毒学应答情况.结果 71例患者中既往应用单一NAs者为25例(以阿德福韦酯为主),序贯或联合应用多种NAs者46例.HBV rtA181T、rtA181V患者病毒学突破时中位血清ALT水平分别为55(15,474)、49(16,183)U/L,P>0.05;血清HBV-DNA的log10分别为5.71±1.02、6.04±0.97,P>0.05;血清HBsAg的log10分别为3.36±0.50、3.64±0.60,P<0.05.用以恩替卡韦为主的挽救方案治疗24周,病毒学完全应答55例(77.5%),病毒学不完全应答16例(22.5%),其中HBV rtA181T、rtA181V患者分别有33(80.5%)、22例(73.3%)达到病毒学完全应答,HBV rtA181T、rtA181V患者病毒学完全应答率相比P>0.05;治疗52周时病毒学完全应答62例(87.3%),病毒学不完全应答9例(12.7%),其中HBV rtA181T、rtA181V患者分别有37(90.2%)、25例(83.3%)达到病毒学完全应答,HBV rtA181T、rtA181V患者病毒学完全应答率相比P>0.05.结论 HBV rtA181T/V突变患者多为序贯或联合应用阿德福韦酯及拉米夫定等多种NAs.HBV rtA181V患者发生病毒学突破时血清HBsAg水平高于HBV rtA181T患者.HBV rtA181T/V突变患者应用恩替卡韦挽救治疗效果满意,但HBV rtA181T、rtA181V患者治疗效果比较无统计学差异.
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